The Big Tent

CTSI 2016 NIH Renewal Proposal Launchpad

Printable Proposal Content

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Preparation and Presentation of an IND Application to the FDA

Proposal Status: 

James H. McKerrow PhD,MD

A major unmet need for the entire UCSF research community is a point person, or small team, that can aid individual investigators in the compilation and writing of an application to the FDA for an IND (investigational new drug). While some IND work has gone on at UCSF, primarily in collaboration with commercial entities, there does not exist an individual with the expertise to help an research investigators identify information that must be included in an IND application for a new small molecule drug, and subsequently to help prepare that application itself.


This shortcoming became clear through efforts of QB 3 personnel to assemble such an application for a newly discovered small molecule in collaboration with the UCSF Small Molecule Discovery Center in Byers Hall. While CTSI provided some information on ethics and individual IND components, there was no single individual who could coordinate such efforts and assist investigators in writing the proposal. In the end investigators on the Mission Bay Campus had to utilize the expertise of personnel in QB 3 who had previous experience in this arena while working in the biotech industry. Unfortunately those individuals have now left the University.


CTSI is the logical umbrella organization to sponsor IND support for research investigators at UCSF. An individual with experience in writing such a proposal and presenting it to the FDA should be recruited and made known to the research community at large. CTSI could use the experience of QB 3 personnel to identify the characteristics of such an individual, and the rich biotech environment surrounding UCSF should prove fertile ground for recruitment.


This individual would meet one-on-one with UCSF research personnel who find themselves at the translational end of a drug development process. They would look over the accumulated information on a drug candidate that the investigator has acquired, and counsel the investigator as to what additional studies the FDA would likely ask for. They would also assist the investigator in preparation of an IND application and presentation of this application at a pre-IND meeting with the appropriate FDA section. Currently, contract research organizations such as SRI international in Menlo Park offer this service at a considerable fee. It would therefore be logical for CTSI to recruit and sponsor such an individual as a member of the UCSF translational drug discovery and development community.

Commenting is closed.

Digital Health Sciences Virtual Core

UCSF Digital Health Sciences Virtual Core

An Open mHealth-compatible Rapid Development Platform & Services

Problem Digital and connected health technologies promise to reduce health care costs and improve health outcomes. Many CTSA researchers have digital health ideas they want to pursue and test, but their institutions are not able to fully provide the resources and expertise they need to build initial prototypes and/or to conduct clinical research using digital technologies.

Solution: The UCSF Digital Health Sciences Virtual Core

The Virtual Core will be a joint effort of CTSI and the Center for Digital Health Innovation (CDHI) to provide “one-stop shopping” for researchers to quickly develop, prototype, field test, and evaluate digital health technologies. The novel technical approach that can be scaled across CTSAs and beyond is to exploit Open mHealth[1], an emerging standard for integrating mobile apps and data, and to build open source Open mHealth-compatible modules for clinical research. The Core will offer 3 major services on a recharge basis to UCSF, participating CTSAs, and other partners:

  1. Rapid Development Services – CDHI is currently choosing a rapid development platform, any of which can be “future-proofed” through use of Open mHealth and other standards. Researchers will work with UCSF developers to script user interaction (e.g., data capture screens, account setup, informed consent, protocol set-up (e.g., n-of-1), reminders, etc.). Development will leverage shared APIs and modules from the growing Open mHealth community, which includes companies (e.g., Qualcomm Life,, health systems (e.g., Kaiser), research centers (e.g., NSF-funded Calit2), and innovation projects (e.g., XPrize). This community is building open APIs to commercial data clouds (e.g., Jawbone, RunKeeper). Use of Open mHealth and other shared code will thus reduce unnecessary duplication while promoting reuse and rapid innovation.
  2. Hosting Services -- UCSF will host the development platform, server, and secure data store with full access control privileges for UCSF and external users. Partners may also host their own data store, platform, and/or server depending on local needs while still benefiting from shared software.
  3. Consultation, Grants, and Resources – The Core will partner with campus entities and other CTSAs to coordinate: 1) technical, design, and methodological consultation services; 2) pilot grants to UCSF researchers under the RAP and T1 Catalyst mechanisms; 3) recruitment assistance and opportunities (e.g., with SF HIP); and 4) streamlined processes (e.g., IRB templates, industry MOUs).

Partners: Potential UCSF partners include QB3, ITA, ISU, and many others. CTSA interest includes UC Davis (on participatory research and business processes), USC, and Cornell (they are hosting their own platform). Industry interest includes, and J&J, (which could link with the Clinical Trials Consortium). Connections to Qualcomm, Intel, etc. open opportunities around devices. From the community, Quantified Self is interested in collaborating around “citizen science,” which could involve SFHIP as well. While UCSF will lead the development of software and methods for core clinical research needs (e.g., recruitment, informed consent, n-of-1 studies, standardized variables, connection to EHRs), other partners can develop their own areas of expertise by contributing or curating open source code or research methods (e.g., mental health, health disparities, longitudinal studies, etc.). By design, this effort can be scaled across additional partners nationally and internationally (e.g., for global health).

Innovation: This proposal is unique in developing and disseminating reusable modules for digital health and clinical research while tapping into open resources from across the mHealth ecosystem. Northwestern’s Purple Robot also offers a scripting and sensor data acquisition platform, but is Android only and is a closed solution that does not ensure integrated mHealth solutions.  

Projected Impact: UCSF will establish clear leadership in the digital health sciences. It will likely lead to new academic-industry collaborations, and will increase the innovation and output of researchers across CTSAs. Finally, through Open mHealth, the resulting software, methodologies, and best practices will reach beyond academia to maximize CTSA’s and NIH‘s ultimate impact on human health.

[1] Open mHealth is a non-profit funded by RWJF and co-founded by Ida Sim, UCSF CTSI’s Co-Director of Biomedical Informatics.

Commenting is closed.

Systems Based Medicine Resource Group

Proposal Status: 


Scale and significance of the problem:  Presently it takes approximately 17 years on average for a physician to adopt a level 1 standard of care.  Part of this delay in adopting standards of care is the absence of a standardized method to disseminate tools for implementation.  The adoption of best practices may require tools, checklists, protocols, procedures, medical center memorandum, and computerized order sets. Currently, each hospital and clinic separately designs their own procedures (evidence and systems-based), protocols, tools and guidelines, which are rarely tested, validated, or optimized. Hundreds of man hours of clinicians’ time go into development of these tools. Often committees working on protocols run out of time, or energy, and the tool is lost. When tools are implemented at one facility, they are rarely validated, tested, optimized, maintained, or distributed to others.  While evidence-based and systems-based medicine may be optimal for patient care from the standpoint of safety and efficacy, the absence of a standardized method to implement, optimize, validate, maintain, and disseminate tools that are developed within a single hospital, renders use of such tools, best practice in concept only, wastes staff resources, and fails to provide the best care possible.


Current approaches (nationally) The VA System has 171 medical centers and more than 1000 clinical sites, with little sharing of protocols, checklists, and systems based medicine tools. VA Central Office will provide regulations on what must be accomplished  but the actual tools, checklists, and approaches are left to individual medical centers to develop.  Kaiser Permanente (KP) has 37 medical centers with a system to share systems based medicine tools. KP has a centralized library of validated order sets, checklists, and tools for systems based medicine.


Proposed approach and why it is innovative:  Establish a centralized systems based medicine resource group to optimize, validate, maintain, communicate, promote, distribute, and disseminate tools developed through systems-based and evidence-based medicine in the VA, KP,  and UCSF facilities, utilizing a central repository system. These tools would assist in the implementation of systems-based medicine.  These implementation tools may include protocols, checklists, Apps, memoranda, computerized order sets, and patient care practices. The medical protocols could be checked using epidemiologic analysis of computerized medical records for safety and efficacy. The cost to produce systems based medicine resources would be dramatically reduced by validating already available tools and then distributing them, rather than have each hospital in a system develop tools individually. In the VA, the work to produce a systems based medicine tool would be cut by a factor of more than 100 (1 protocol used in 171 hospitals, rather than each hospital developing their own independently).


Potential Partners:  The systems based medicine resource group could collaborate with Kaiser Permanente, the VA, and UCSF to share systems based medicine tools. KP has borrowed protocols from the SF VAMC. KP has an extensive library of these tools which could provide a basis for the library.


Projected impact, if possible, use back of the envelop calculation to provide quantitative support: A central repository system that effectively disseminates validated tools for implementing best practices would improve availability of evidence and system-based resources to clinicians,  reduce the time and cost for adoption of best practices thereby improving patient care.The result would be improvements in patient outcomes, reduction of mortality rates, reduction of operating costs, improved efficiency, and wider use of evidence and systems-based medicine. Use of individual protocols has reduced mortality rates by 35-50%. Cost savings in the VA are estimated to be a minimum of $1 billion dollars per year.

Commenting is closed.

The Global HCV Treatment Revolution: A Response Model for Future Challenges and Opportunities

Scale and significance of the problem

New pathogens and developments in diagnostics and therapeutics are transforming healthcare.  Comprehensive planning for paradigm-changing advances, when possible, can mobilize the full range of expertise available in a complex institution like UCSF and in our community partners. Systematic planning can identify new research opportunities, reduce institutional costs and improve patient care.

One healthcare challenge that can serve as exemplary for other implementation opportunities is the treatment of hepatitis C virus (HCV) infection. HCV is a large epidemic-more than 200 million cases worldwide- causing substantial morbidity and mortality. Current treatments have serious limitations but new drug development has been remarkable with soon-to-be-approved drugs achieving close to 100% cure rates after only 12 weeks of use with low toxicity. These drugs will cause an explosive increase in treatment volume over the next 1-2 years despite a high cost (est. $70,000).

Lessons learned in this demonstration project will apply to pending breakthroughs including the discovery of effective drugs to prevent or treat Alzheimer’s disease and the identification of genetic causes of common diseases with resulting targeted interventions.

Current approaches (nationally)

No comprehensive model of HCV treatment exists and no other attempts have been presented that approach this proposal in establishing a comparison for implementing efficient systems for other diseases and new challenges. HCV care is currently fragmented, delivered by hepatologists, infectious disease specialists of general internists with limited collaboration or involvement by teams as proposed here.

Proposed approach and why it is innovative

We will design optimized systems of care and research organization to monitor, evaluate and adjust the screening of patient populations, to stage underlying liver disease and to initiate therapy when indicated. As each of the three primary UCSF-related medical centers; Parnassus, San Francisco General Hospital and the VA Medical Center have large but demographically distinctive patient populations and payment systems, comparing experience through data sharing will enrich the development of the HCV response model and increase its generalizability. Linking the information collected across UCSF with data from the network of the five University of California medical centers through the UC BRAID system of CTSI with 12 million covered lives will further strengthen the lessons learned from this project, representing an innovative use of “big data” in healthcare.

The HCV model project will be dynamic. As drugs are approved and as demand for care increases, the team will monitor data from each medical center to compare population screening rates and success in each step of the treatment “cascade” familiar from the HIV experience.

The project will be innovative and outward looking in working from the start with community members and with experts at UCSF expert in engaging the very different communities most affected by the HCV epidemic.

The HCV project will continually attend to how the systems found effective might be similarly deployed against other health care imperatives, particularly as the entire structure of American healthcare adjusts to the rollout of the Affordable Care Act.

Potential partners

The project will build from an existing cross-campus planning group of clinicians, basic scientists and epidemiologists, adding information technology to created data linkages across the three UCSF medical centers and with UC BRAID and economists and pharmacists to model cost and policy implications. Community members and community engagement experts will increase project impact and broad participation. Implementation scientists will develop models which can inform other healthcare challenges an d global health experts will consider applications in resource-limited settings.

Projected impact (estimate resources needed)

HCV infects 200 million worldwide. Designing a coordinated and effective response to new curative treatments would have an immediate benefit to those affected, decrease further transmission and provide a crucial model for other emerging healthcare priorities.


Supporting Documents: 

Commenting is closed.

Exchange Marketplace for Drug Discovery and Development Resources

Drug development is a complex and resource-intensive process, with few academic institutions able to provide its translational researchers with the all the necessary infrastructure and resources to advance promising targets or early-stage molecules to validation. We propose to create an Exchange Marketplace – a framework in which a university can offer its unique capabilities and core resources in drug development in exchange for those that are not readily available on that particular campus.  We propose to utilize the UC BRAID (Biomedical Research Acceleration, Integration & Development) network and the Drug and Device Discovery and Development (D4) workgroup within BRAID to engage the five participating UC campuses of BRAID into the Marketplace.


A recent summit of the BRAID D4 workgroup in April 2013 made it clear that no single campus has all the necessary core resources to do drug development in-house. The summit also helped identify some of unique drug development infrastructure and core resources on each of the D4 campuses which can be shared via the Marketplace.  For example, UCSF leads the group with a state-of-the-art small molecule screening facility and medicinal chemistry capability (SMDC), while UCSD can contribute access to its unique marine natural products library.  UCD can contribute its GMP manufacturing facility and UCLA its GLP Toxicology facility – such facilities are not available at any other D4 campus.  These aforementioned facilities are meant to be representative examples of unique resources on each campus, but they demonstrate the increased breadth of capabilities that immediately opens up to the research community once the campuses agree to the exchange.


We propose that each campus contributes a chosen $ amount of services, linked to specific cores, to be offered to other campuses.  In return, each campus will be eligible to receive the amount of services on the marketplace equal to its contribution.  A process will be set up to issue the awards (in the form of services) to the investigators of the participating campuses.  The awards can be issued through a multi-campus RFP process, with a review team comprised of representatives from each campus.  Alternatively, each campus can conduct its own evaluation of proposals and recommend projects to receive the awards. 


Exchange Marketplace for drug development resources brings together and leverages the strengths and capabilities of each of the participating institutions.  It provides the research community with the knowledge of the types of services available on sister campuses.  It can seed collaborations between researchers across campuses.  Exchange Marketplace can offer pre-negotiated rates on a fee-for-service model, removing the IP roadblocks to collaborations.  A planning grant through the Big Tent Open Proposal mechanism could allow us to evaluate the feasibility of establishing such marketplace, gathering campus-level support from the participants, and refining the list of cores and facilities interested in participating in the program.


The recent Institute of Medicine review of CTSA programs strongly emphasizes a need to engage in substantive and productive collaborations as well as develop and disseminate research resources while focusing and leveraging on individual CTSA institution’s strengths.   The Exchange Marketplace does precisely that by linking the resources of the 5 BRAID participants (UCSF, UCD, UCLA, UCI, UCSD) and making them available to the research community.  Once the program is established and successful, this platform can be extended to other areas of research and development (e.g. Device development) and/or to other institutions.  Initially, however, we believe that the network comprising the BRAID D4 provides a powerful foundation for establishment of the program. 

Commenting is closed.

"Speed-Networking" to Drive Novel Translational Research Connections


Investigators lack opportunities for novel interactions with partners with whom they do not ordinarily collaborate, either because they haven’t had the opportunity to meet each other by virtue of operating in different disciplines or locations, or because there has been neither a straight-forward mechanism nor incentive to look outside one’s usual circle of  partners.



  1. Provide an opportunity for scientists to meet  research, community, and/or community partners outside their usual circle of collaborators in order to foster a broader network  partnership through a designated networking event;
  2. Provide seed-funding for up to three collaborative projects per event in the amount of approximately $5,000 each for feasibility pilot studies that encourage new collaborations, new methods, and/or innovative interdisciplinary research approaches to outstanding translational healthcare issues; and
  3. Aide in the transition of funded projects to further larger, enabling projects.



In an effort to encourage collaborations across disciplinary, geographical, or institutional boundaries, the Research Development Office (RDO) will facilitate a series of interactive events that will bring targeted investigators and community, affiliate, and/or commercial partners together and incentivize innovative collaborations.



These “Speed-Networking” events will provide a structured environment in which each researcher will have an opportunity to meet potential outside collaborators in a prescribed format.    Additional social interaction time will then allow interested parties an opportunity to continue specific threads of inquiry.   Potential partners will ultimately complete a card indicating their interest in speaking further with one or more of the participants.  The RDO will manage the follow-up from these events.


The particular focus area for any single event could be selected strategically to support larger campus initiatives or be uniquely chosen to “test the waters” for new areas of potential strategic importance.




Initially, ten separate Speed-Networking events will be planned over the course of a year.  The RDO will work with CTSI leadership to identify both the specific focus of an event and the cadre of participant researchers and outside partners.  The number of participants will be capped at 30 to ensure adequate interaction time.  The RDO will manage all the logistics, including invitations, securing meeting space, arranging food and beverage as needed, and setting-up the event space and materials.  The RDO will also lead participants through the event and manage all follow-up.



  • “Slush” Time (20 min.):  the success of this event in part depends on all attendees being punctual; light refreshments, therefore, will be available during this time to allow for casual conversation and serve as “slush” time for stragglers to arrive
  • Introduction (5 min.):  the RDO team leader will introduce the program, focusing on the intent, format, and financial incentive
  • Rotations (1 hr.):  four-minute rotations between each set of attendees, allowing all investigators to meet  all potential partners around a short set of pre-designed questions (e.g., who, what, what if, and how might we)
  • Free Association (20 min.):  people are able to reconnect with a partner with whom there is a “spark” and pursue their shared interest a bit more, potentially developing a more concrete vision of a collaborative project
  • Next Steps (10 min.):  each attendee will fill out a card identifying her/his top three choices for collaboration; the RDO  team leader will close the event by informing participants of next steps and timeline



After the event, “matches” will be identified by the RDO team based on participants’ mutual identification.  The RDO will reach out to these partners, inviting each “match” to prepare a simple, two-page proposal describing their feasibility or pilot project and associated budget needs of up to $5,000.  The target goal would be to have these due within three weeks of the event, if possible.   CTSI leadership, with the assistance of the RDO, will make the final funding decision, based on both the likelihood of project success and a fit with CTSI strategic goals.  The goal is to make these funding decisions within about five weeks of the event, if possible.  For projects not outlined or funded as a result of this event, it is important to note the tremendous value in the networking component for potential future collaborations and faculty satisfaction.  For funded projects and where appropriate, the RDO will collaborate with the Office of Innovation, Technology and Alliances (ITA), as well as the appropriate UCSF community engagement office, to foster success in the translation  of the idea.



There are three specific returns on investment of the Speed-Networking event that will be measured:  1) the number of researchers that participate in a networking event will be counted; 2) the direct benefit to future  collaboration activity made possible by supporting the generation of preliminary data and providing evidence of prior collaboration; this will be measured by following funded projects and capturing the percentage that go on to receive related funding from extramural sources, initiate new contracts, or otherwise move to further the collaboration; and 3) the participant satisfaction value, which will be measured through a short survey instrument sent at the end of each event.  The RDO will track and report these measures.



In the first year, we plan to facilitate ten speed networking events.  Each event will target 30 participants, leading to the funding of two or three $5,000 pilot proposals.  While the RDO will leverage resources from its Building Teams for Innovative Research (BTIR) program personnel for this Speed-Networking program, additional resources will be needed to facilitate the program at a rate of approximately one FTE per three events.  We also plan to minimize the logistical event costs by utilizing freely available facilities on campus wherever possible.  The anticipated costs are presented in Table 1 below.



Cost for 3 Events

Costs for 10 Events

Event logistics, including beverages, food, paper goods, copying (assuming ~$500 per event)



Pilot Proposal Award, assuming 30 awards per event, at $5,000 per award



Two FTEs, at $80,000 each



Total Annual Proposed Budget



Commenting is closed.

Improving Education and Treatment of Newborns with Disorders Detected in the California State Newborn Screening Program through Linking Resources of the CTSI with the State Genetic Disease Screening Program

Primary Author: Elliott Vichinsky
Proposal Status: 

The IOM has called for the CTSAs to expand research on children. The CTSI and the California Department of Public Health have a common vision of improving the health of children through newborn screening programs for genetic disorders. California has been a pioneer in developing new approaches to diagnosis, education, and treatment of disorders detected in the newborn period. Currently, several million newborns in California are screened for 21 genetic disorders each year. 

Overall, screening disorders are identified in 1 of every 500 births.  The data indicate hereditary disease expression is strongly affected by ethnicity/race. In California, there are 16 separate racial/ethnic groups at disproportional risk for specific genetic disorders.  For instance, 1 in every 80 Southeast Asians has a screening disorder.  Asian East Indians have the highest prevalence of endocrine disorders, Native Americans have a disproportional prevalence of cystic fibrosis, and metabolic disorders are highest in the Middle Eastern population.

Systematic problems, magnified by the diverse cultural and economic factors affecting the target population, impair the ability of the California State Newborn Screening Program to optimally reach its public health goals.  These goals include appropriate evaluation, performance monitoring, and access from birth through young adulthood to specialized treatment for all persons affected by screening disorders. Furthermore, significant numbers of families with affected newborns currently lack an informed provider in a medical home, do not have access to the latest therapy, and/or are not able to obtain counseling.

The goal of this proposal is to form an innovative partnership between the California Department of Public Health’s Genetic Disease Screening Program (CDPH BDSP) and the CTSI. The decision makers at the CDPH BDSP are “on board” and eager to have an opportunity to develop these ideas in a planning period.  Likely CTSI partners include the Comparative Effectiveness Large Dataset Analysis Core (CELDAC), the CTSI Community Engagement Program, CTSI Clinical Research Services, and the Children’s Hospital & Research Center Oakland, which runs the state screening program for hemoglobinpathies and has worked with the state screening program for many years. Other UCs are also potential partners.

This partnership will have several objectives:

(1)    Improve medical homes through provider education— The initiative will foster an active network of medical home physicians, and will develop provider education programs focusing on standard of care practice guidelines for each disorder, leading to better quality of care and improved guideline compliance. 

(2)    Develop a patient registry-- In collaboration with the medical homes, the initiative will develop an active registry of patients identified in the newborn screening program. These patients will receive educational services through multimedia approaches and have access to clinical trials.

(3)    Improve the infrastructure to conduct translational research-- The provider network and patient registry will provide a platform for conducting longitudinal studies for rare diseases, development of biomarkers, and a biologic bank for research, and will greatly facilitate access to patients and data for the development of new therapies.

Strategically combining resources of the CTSI and the CDPH BDSP will open up new and unprecedented research avenues from T1-T4.  California is uniquely positioned to utilize its screening registry for translational research purposes. We believe that a small planning grant will allow us to develop these ideas into a compelling project that would greatly strengthen the CTSI renewal and would ultimately serve as a model for other states. 

Commenting is closed.

Bay Area Nutrition and Health Initiative: A Novel Family and Community-Based Approach for Addressing the Gap Between Nutrition Science and Improvements in Nutrition-related Health Outcomes

Primary Author: Ronald Krauss
Proposal Status: 

Poor nutritional practices contribute inordinately to the major diseases affecting public health and hence the health care economy. Among these are obesity (recently classified as a disease in itself) as well as heart disease, hypertension, stroke, diabetes, and likely, some forms of cancer.  While weight loss has been a focus of trials aimed at improving disease risk, studies such as the recent report of the NIH Look Ahead trial have failed to demonstrate that diet-induced weight loss reduces disease outcome (in this case, cardiovascular disease). Notably, in the New England Journal of Medicine editorial accompanying this report (July 11, 2013), it was stated that "different and novel strategies [will be needed] to maintain initially large effects on weight and other risk factors over a period of several years".


To address this need, we propose developing and implementing an innovative family and community-based nutrition counseling and skills training program that is informed by our separate experiences with adults and children, but will now aim at working with families in a more integrated approach.  This novel program affords the opportunity to evaluate genetic and cultural influences on metabolic health and nutritional needs; to generate and apply new knowledge regarding effective and individualized nutritional guidance; and to evaluate the effectiveness of this approach vs. conventional practices on specific health-related outcomes (e.g., adiposity, blood pressure, metabolic profiles).  


Our proposed Bay Area Nutrition and Health Initiative (BANHI) will recruit families - as defined by at least one adult and one biological child - into a comprehensive clinical research program that provides regular health assessments, education and skills training, including mindfulness and food preparation, and a unique plan for long-term follow-up (at least 5 years). Key features of BANHI are: 1) it teaches skills to the unit, i.e. the family, which can most effectively implement behavior change; 2) it is simultaneously preventive and therapeutic; 3) it targets the lifespan, including the perinatal period; 4) it creates a research cohort that will be an invaluable resource for studies in the laboratory and the clinic aimed at increasing knowledge and evaluating the efficacy of therapies (nutritional and other) aimed at reducing risk of chronic disease and 5) it has the potential to generate laboratory and clinical data, as well as a biobank of archived samples, that may be used by investigators to understand the basis for inter-individual variation in disease risk and responses to dietary modifications.


Importantly, the BANHI embraces the entire translational spectrum (T1-T4) with participation of researchers, clinicians, and public health experts. It capitalizes on the combined scientific and core resources as well as expertise of Children’s Hospital & Research Center Oakland and UCSF (e.g. Clinical Research Services, Community Engaged Research and Participant Recruitment Services), as well as the UC Berkeley School of Public Health.  CHRCO, in particular, has access to a large number of at-risk families with diverse racial, ethnic, and cultural backgrounds that would benefit from this program. Furthermore, potential partnerships with other health organizations, including the Ethnic Health Institute at Alta Bates Summit Medical Center and La Clinica de la Raza, will allow for the Initiative to expand its reach to an even greater number of families of underserved communities throughout the Bay Area. BAHNI may serve as a model for other academic medical centers and national guidelines committed to achieving long-lasting improvements in the risk of nutrition-related chronic disease.

Commenting is closed.

UCSF Center for Innovation Practice: Dissemination and Diffusion

Proposal Status: 

1. Scale and significance: Creative and groundbreaking T-2-T-3 Innovations in health care and community delivery have been developed and tested within many UCSF settings. While some successes have been achieved, the campus has not been able to leverage the full power of these innovations; limitations in the scalability of even the strongest and best-tested innovations occur. Many of the innovations are disseminated and potentially exported externally to UCSF, but few systematic approaches exist to internally marshal innovation for internal consumption in potential “next circle” of settings for replications and further testing, adaptation, and cultural refinements. Few systematic approaches for collecting information on these “home-grown” initiatives exist, precluding “mindful” and meaningful expansion into other “neighborhoods”.

2. Current Approaches (nationally). Our “distributive” nature lends to lost opportunities for cross-fertilization, delays as new initiatives are tested, lack of recognition of previous institutional history that could help avoid common, but time- and expense-intense errors. National innovation “explosion” being tested nationally could have great utility for UCSF/UC-wide, in an effort to make information more readily available.

3. Potential Approach: Establish a campus-wide Innovation Bank. Readily available and consistent information on the innovations, including how they were established, funded, who was involved, how did the model evolve, outcomes, evidence of effectiveness (i.e., cost-savings, increased patient satisfaction, improved use of existing resources) has not been centralized as we aim to develop additional quality and cost-reduction improvements. Additional strategies are needed for sharing the results of the innovations: short videos, podcasts, retreat briefings, panels. A “concierge” element, matching individuals ready to implement new initiatives with those who might have had relevant experience. Evaluation of the process of matching, as well as utility of the repository, is needed. The clearinghouse could also help in the diffusion of practice for those interested in identifying “works in progress”, wherein the innovation is still in the initial process of implementation. “Crowd-sourcing” could be tapped, contributing to ideas, in real time.

4. Partners: An Advisory Board comprised of Clinical Chairs would guide the development and implementation of the repository; proposed activities would also coordinate with the Implementation Science endeavor, Center for Healthcare Value, etc. Other CTSA/UCOP could participate once the initial resource is launched at UCSF.

5. Projected Impact: A collective fund, supported in part by the Clinical Departments, Schools, and Medical Center, would help create an “incentive” matching fund to implement innovations (UCSF and elsewhere) that have been shown to have success in improving quality, safety, outcomes, cost containment, and patient satisfaction. A process for applying for funds (building on campus efforts in Implementation Sciences) will be established and a review panel will select prioritized innovations, continuing to monitor and provide oversight as the replications are implemented. Leveraging innovations that work could help reduce substantial medical costs.

Commenting is closed.

Harnessing the Law for Translational Science: The UC Initiative on Translational Science and the Law (ITSL)

1. Scale and Significance: Law shapes the effectiveness and impact of research translation across the T1-T4 continuum. Effective T1 involves contracts and intellectual property; T2 researchers navigate human subjects regulation; healthcare policy shapes T3 impact; and law itself is a powerful lever for change at T4.

Recognizing law’s impact, we seek to accelerate research by providing tailored legal support at all points of the translational continuum. To do so, we propose a UC-wide Initiative on Translational Science and the Law (ITSL). This Initiative will enable investigators to more-readily address legal challenges to research translation and to recognize and leverage opportunities to use the law to enhance their translational impact.

2. Current Approaches: The Initiative on Translational Science and the Law (ITSL) extends the work of the UCSF/UC Hastings Consortium on Law, Science, and Health Policy – the only effort of its kind in the US, to our knowledge (see below). The Consortium has brought together health researchers at UCSF and law faculty at UC Hastings to address challenges and leverage opportunities at all four translational points.

  • T1: The Consortium sponsored a UCSF forum on gene patenting and is contributing to a precision medicine workgroup on regulation and policy.
  • T2: The Consortium is contributing to EngageUC, an NIH project that is leveraging UC BRAID to develop harmonized processes for biobanking.
  • T3: With CTSI pilot funding, the Consortium is working with health policy researchers to identify legal strategies to foster price transparency in healthcare purchasing.
  • T4: With CTSI pilot funding, the Consortium has brought together obesity researchers with local regulators and public interest lawyers to develop legal strategies to reduce the health burden of excess sugar consumption.

3. Proposed Approach and Why it is Innovative: ITSL will build on the success and structure of the UCSF/UC Hastings Consortium. First, we will establish a network of legal experts at multiple UC campuses and will make this expertise broadly available to translational researchers (see Potential Partners, below). Second, ITSL will perform outreach to health researchers throughout UC to raise awareness of this service. Proactive outreach – e.g. attending presentations where investigators discuss research with legal implications, leveraging information in CTSA Profiles, etc. – will be particularly important. Our Consortium experience suggests that researchers often recognize when they face legal challenges but may be unaware that their problem is actually solvable. Finally, once investigators recognize that help is available, ITSL staff based at the Consortium will field questions, clarify requests, work with Consortium faculty to identify appropriate ITSL-network experts, and propose tailored solutions. The Consortium has developed a range of such tailored solutions. Well-circumscribed questions, e.g. a human subjects question, may be solved via brief consultation. But ITSL will also be able to respond to ongoing needs, e.g. developing a legal core to bolster T4 translation in a multi-site public health intervention study.

A recent examination of CTSA law and policy initiatives found no partnerships similar to the Consortium or ITSL. All CTSAs help guide investigators across regulatory hurdles, but few make legal expertise available to accelerate translational research per se. It is likely that legal issues in research translation are currently siloed: T1 in technology transfer, T2 in ethics and compliance, and T3-T4 in policy and public health research. ITSL seeks to change that.

4. Potential Partners: The UCSF/UC Hastings Consortium will provide a foundation for ITSL. UC Hastings and CTSI connections with law schools and translational researchers, respectively, will allow ITSL to recruit experts and conduct outreach. On the legal side, the Program on Understanding Law, Science, and Evidence (PULSE) at UCLA School of Law and the Health Law Program at UC San Diego and California Western Law School offer strong partnership opportunities. On the translational science side, UC BRAID, EngageUC and precision medicine create teams of investigators whose research programs will benefit from ITSL support. Other CTSAs or networks, such as the eMERGE network of DNA biobanks, provide additional opportunities for partnerships nationwide.

5. Project Impact: The experiences of the UCSF/UC Hastings Consortium illustrate the potential impact of this initiative. The Consortium has contributed to NIH and private grants totaling more than $6 million in the last three years. The Consortium has sponsored 50+ lectures and symposia and contributed to over a dozen white papers and publications. Based on this experience, we project the potential impact of ITSL could be substantial.

Commenting is closed.

Telemedicine and Translational Research

Primary Author: David Durand

Advancements in technology, greater acceptance of remote communication by patients and insurance providers, and a trend toward an  increasing demand for providers and cost effective approaches will ensure telemedicine will play a much large role in the future of healthcare delivery than it does currently.   T4 research on outcomes, efficacy, cost, quality of care, and patient satisfaction related to the various applications and potential applications of telemedicine has grown significantly over the past decade, and there are now two journals dedicated to telemedicine.   However, little research to date has been with the pediatric or diverse rural or urban underserved populations.  The Institute of Medicine recently published its report on advancing translational research among the CTSA programs and recommended a greater focus on both children and ethnic minorities.

Largely with federal funding, the California Telehealth Network has built an infrastructure of high-speed broadband throughout California.  With expertise in numerous pediatric specialties and diverse population populations and a progressive spirit, CTSI could be the hub of research at the forefront of telehealth research.

Studies on outcomes, patient satisfaction, cost effectiveness and ROI, and comparative effectiveness may be applied to timely topics such as but not limited to:


•             Tele-care coordination, home health 

•             Remote monitoring of persons nursing homes

•             Tele-care for persons in correctional facilities and other institutions

•             Telepsychiatry and behavioral medicine

•             Oversight of non-MDs if scope of practice bills pass (SB 491,SB 492, and SB 493)  

•             Access to specialty care in rural areas of California

•             Provider training


In addition to research on telemedicine, the utility of these new technologies within the research enterprise has barely been tapped. There are numerous applications and opportunities to both study and utilize new communication technologies within translational research to facilitate participant interaction and involvement and oversight more non-academic community research locations. 

A CTSI planning grant will allow a select group of researchers across partnering institutions to secure partners, define its goals, and narrow its focus.  Potential partners include the UCSF Telemed Dept., the CTSI Community Engagement Program, Children’s Hospital & Research Center Oakland, and the UC Davis Pediatric Telemedicine Project. Other potential partners include SF Bay CRN, UC Davis, UC Berkeley, and various organizations around the state.

A coordinated effort among and between UCs in California and community partners could serve as a national model and source of expertise for the study of telehealth clinical applications and the utility of telehealth applications within translational science. 

Commenting is closed.

An initiative to expand CTSI Study Recruitment in the East Bay

Primary Author: David Durand
Proposal Status: 

The pace and efficiency of recruitment of participants into a study is typically the limiting factor for how quickly a clinical trial can be completed.  Maximizing the efficiency and scale of recruitment for a study means the study can be completed sooner, use fewer resources, and/or increase the study’s sample size, and therefore its utility to science.

The CTSI’s Participant Recruitment and Study Management Services (SRS) program aims to assist UCSF investigators with study recruitment, screening, and enrollment of participants into USCF clinical research services, as well as provide tools, education and outreach related to the recruitment of research participants. Despite these resources, recruitment in San Francisco can be especially challenging. In particular, there is simply a limited pool of children living in San Francisco for pediatric studies, as well as a limited pool of African Americans of all ages.

Fortunately there a population of more than 2 million individuals in the East Bay which, for the most part, has not been tapped for UCSF-based clinical trials. However, few investigators are familiar with how to access these communities, and in any case, the time and inconvenience of going into the city likely prevents the eager participation of most individuals outside of San Francisco.

The CTSI satellites sites at Children’s Hospital Oakland and Kaiser Permanente in Oakland have been utilized primarily by investigators based at those institutions. Very recently, there have been efforts to expand recruitment into the East Bay for trials originating with UCSF investigators, as well as hosting study visits at that locations. The positive impact on recruitment from these locations cannot be understated and has resulted in additional funding for UCSF.

CTSI’s goal with the renewal launch pad is “to involve the broadest community possible of UCSF faculty, affiliate organizations, community partners, etc. to help identify and plan activities that will substantially improve translational research at UCSF, regionally and nationally.”

The proposed initiative would serve to significantly strengthen translational research based at UCSF by facilitating the ability of investigators of clinical trials to outreach and enroll a “new” population of diverse children and adults, and to conduct study visits in the East Bay.  

Potential partners include CTSI SRS program, CTSI Community Engagement Program, Children’s Hospital & Research Center Oakland, Gallo Center, Kaiser Permanente, the Center for Information and Study on Research Participation (CISCRP), and the OmniScience Mobile. A planning grant would allow interested parties to develop these basic ideas into practical strategies. Over time a recognition among investigators to "think outside of SF" would become normalized. 

 Successful implementation of the proposed initiative in the next CTSI cycle has enormous potential to improve study efficiency, reduce costs, and increase sample size of scores of CTSI studies, as well as improve the competitiveness of future grant proposals.

A large scale, coordinated and strategic effort to expand the CTSI recruitment catchment area, particularly if successful (as early attempts have indicated it should be) could influence similar efforts at other CTSA sites and for research centers in general. 

Commenting is closed.

Poverty Matters: Incorporating Social Determinants of Health into the Medical Model

Proposal Status: 

Adverse social circumstances like community violence, unstable housing, food deserts and poverty can have dramatic, negative impacts on the health of vulnerable children. In safety-net settings, the prevalence of these adverse social circumstances is alarmingly high. A 2007 study in a pediatric emergency department demonstrated that over 97% of presenting families had at least one unmet basic social need; over 48% of families reported that within the last 12 months they had either been threatened with or experienced utility shut-offs; and over 30% of families said that they had either reduced the size of their meals or skipped meals because they did not have enough money for food. [1] These collective social needs, often referred to as social determinants of health, are well-documented to cause psychological stress in families.[2] [3]

There is an increasing body of literature that shows an association between aggregate psychological stress over the life course[4] and the risk for the development and severity of numerous chronic diseases[5]. The combined physiological response to environmental, social, and personal stressors is referred to as allostatic load[6]. Allostasis refers to the body’s ability to adapt to stress (physical, psychological, and social) through activation of the sympathetic nervous system, hypothalamus-pituitary-adrenal axis and metabolic system. As the allostatic load increases, this system breaks down and leads to the dysregulation of stress hormones, which causes disease or worsens disease states, and leads to behavioral/developmental and potentially lifelong psychiatric problems.

Correlating disease processes with adverse childhood experiences, and incorporating indicators of social stress and allostatic load into the medical model represents a new frontier in disease management.  There is a need for research to more firmly define the link between social stressors, disease, and the healing process, and to understand the impact of epigenetics on brain development and its relationship to the toxic stressors of poverty.

Incorporating a “Social Determinants of Health” framework into a mechanistic model of disease represents a new direction in disease prevention and management. It would necessitate building a new system of identifying patients’ needs, and would mandate including social determinants of health in disease prevention strategy. It would allow for new areas of drug development,  transform health care delivery systems, health care utilization and training of health care providers. The “Social Determinants of Health” approach has broad implications for both bench research and clinical trials at UCSF and throughout the country.  Moreover, allostatic load is a concept that is exceptionally well suited for T1-T4 research. A CTSI initiative investigating allostatic load would establish CTSI as a leader in this innovative approach to disease and help encourage a paradigm shift in translational research and medicine.

A primary partner on this project would be the UCSF Center for Genes, Environments & Health, which is already doing social and biologic research on allostatic load. In addition to the translational sciences research team, partners include Children’s Hospital & Research Center Oakland (CHRCO), which has a high volume of children significantly affected by social stressors. The Institute of Medicine (IOM) recently published its report on advancing translational research among the CTSA programs and recommended a greater focus on both children and ethnic minorities, with CHRCO this recommendation will be met. The proposed project will appeal to a diverse team from multidisciplinary backgrounds and we foresee the CTSI Community Engagement Program, other UC health care providers, epidemiologists, sociologists, anthropologists, public health experts, and national groups already addressing issues of poverty and health as potential partners.  Lastly, partnerships with community agencies will be essential in building a foundation for community-based participatory research. 

[1] Hanson M, Lawton E. Between a rock and a hard place: The prevalence and severity of unmet legal needs in the pediatric emergency department setting. Medical Legal Partnership for Children. 2007

[2] McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med 1998;338:171-9.

[3] Evans GW et al. The environment of poverty: multiple stressor exposure, psychophysiological stress, and socioemotional adjustment. Child Development 2003;73(4):1238-1248.

[4] Halfon N, Hochstein M. Life course health development: an integrated framework for developing health, policy, and research. Milbank Q 2002;80:433-79, iii


[5] Marmot MG et al. Health inequalities among Britist civil servants: the Whitehall II study. Lancet. 1991 Jun 8;337(8754):1387-93


[6] Wright RJ et al. Seeking an integrated approach to assessing stress mechanisms related to asthma: is the allostatic load framework useful? Am J Respir Crit Care Med 2013;187:115-6


Commenting is closed.

National Repository for Stem Cell Derived Neurons

Primary Author: Bruce Miller
Proposal Status: 

The failure of large clinical trials for Alzheimer’s disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis and Parkinson’s disease (PD) are forcing the field to consider more targeted treatments for genetically homogeneous cohorts. Precision medicine approaches to the diagnosis and treatment of patients offer huge opportunities to advance the dementia field. New trials for AD patients with presenilin-1 mutations and FTD patients with progranulin and tau mutations have already been started or are being considered.  

Dr. Shinya Yamanaka brought a revolution to stem cell technology by delineating a method to convert skin cells to induced pluripotent stem cells (iPSCs).  This approach has facilitated development of new models of neurodegeneration for patients with FTD-related mutations of progranulin (1,2) or C9orf72 (3). Similarly, iPSC-based modeling of the detrimental effects of apolipoprotein E4 and the tau polymorphism A152T (Yadong Huang, personal, communication) is facilitating a precision medicine approach to the determination of disease effects of specific genes. Via iPSC technology, large quantities of neurons can be produced allowing exploration of the pathological consequences of genetic polymorphisms while simultaneously allowing drug screening of neurons from patients with genetically caused forms of dementia. (4)

We propose to create through UCSF’s CTSI a national core of neurons from patients with both sporadic and genetic forms of Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson’s disease and other rare forms of dementia. Selected investigators will study and manipulate these neurons in order to develop model systems for the major mutations that cause AD, FTD, ALS and PD. Simultaneously, age-matched control neuronal lines would also be generated for comparison studies. Large numbers of these neurons would be created for and distributed to other CTSI sites investigators and scientists across the world, requesting the use of these valuable cells.  

Comprehensive clinical phenotyping would be performed on the participants in this project that would include clinical characterization (demographics, cognitive, motor and imaging data), and family history.  Whole genome sequencing of the cells would be performed at UCLA and transciptome analysis would be done at UCSB. The resulting multidimensional data would be incorporated into the UCSF Precision Medicine Knowledgebase, linking it with related neuroscientific datasets and analytic resources to maximize its value for the larger research community. The project would be led by UCSF’s Memory and Aging Center (Bruce Miller, Kate Rankin, Aimee Kao), the Gladstone Institute (Yadong Huang), the Broad Institute (Steve Haggarty), UCSD (Irene Litvan), and UCLA (Dan Geschwind and Giovanni Coppola). Partial support for the study will be supplied by three private foundations, the UCSF NIA supported by an Alzheimer Disease Research Center (Miller), and a grant supported by the NINDS (Huang).



1. Almeida S, Gascon E, Tran H, Chou HJ, Gendron TF, Degroot S, Tapper AR, Sellier C, Charlet-Berguerand N, Karydas A, Seeley WW, Boxer AL, Petrucelli L, Miller BL, Gao FB. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 2013 Jul 9.

2. Almeida S, Zhang Z, Coppola G, Mao W, Futai K, Karydas A, Geschwind MD, Tartaglia MC, Gao F, Gianni D, Sena-Esteves M, Geschwind DH, Miller BL, Farese RV Jr, Gao FB.

3. Induced pluripotent stem cell models of progranulin-deficient frontotemporal dementia uncover specific reversible neuronal defects. Cell Rep. 2012 Oct 25;2(4):789-98.

4. Cenik B, Sephton CF, Dewey CM, Xian X, Wei S, Yu K, Niu W, Coppola G, Coughlin SE, Lee SE, Dries DR, Almeida S, Geschwind D, Gao FB, Miller BL, Farese RV Jr, Posner BA, Yu G, Herz J. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J Biol Chem. 2011 May 6;286(18):16101-8.

5. Zhao WN, Cheng C, Theriault KM, Sheridan SD, Tsai LH, Haggarty SJ.  A high-throughput screen for Wnt/β-catenin signaling pathway modulators in human iPSC-derived neural progenitors. J Biomol Screen. 2012 Oct;17(9):1252-63.

Commenting is closed.

Administrative Data Concierge Service

Challenge: Many UCSF researchers are interested in questions about human health and the delivery of health care services that could be studied using large administrative datasets, such as those generated by the Centers for Medicare and Medicaid Services (CMS), the California Office of Statewide Health Planning and Development (OSHPD), and agencies that collect vital statistics data (e.g., birth certificates, death certificates). While some UCSF researchers have conducted important research with these datasets, expanding the pool of researchers who work with them is challenging for several reasons. Organizations that produce these datasets often have difficulty responding to requests promptly due to limited resources and competing priorities. In addition, extensive programming is often required to transform the raw data into usable information. For some research questions, researchers also need to link vital statistics records with administrative data on the delivery of health care services. Because many of the publicly available versions of data sets are de-identified, linking such datasets typically relies upon probabilistic matching algorithms. The complexities and error-prone nature of probabilistic matching represents a barrier to the full exploitation of administrative and vital statistics data by researchers who are not experts in these techniques.

Solution - Data Concierge Service: Building upon resources for analysis of large, public datasets that are already available to UCSF researchers through the Comparative Effectiveness Large Dataset Analysis Core (CELDAC), this project would establish a concierge service that would assist UCSF researchers in accessing large administrative datasets. A ‘special access’ data manager who would simultaneously be employed by UCSF and agencies that collect administrative data (OSHPD, CA Department of Public Health, CMS) would link records across datasets. The data manager would have expertise in the use of deterministic and probabilistic matching algorithms to merge datasets using unique identifiers (where available) and other variables such as date, age, gender, and zip code. The data manager would generate customized datasets that are tailored to researchers’ specifications, create de-identified versions of them, and deliver them to requestors (probably through MyResearch). The data manager and CELDAC’s principal investigator would work with investigators to ensure they secure the approvals needed to analyze and report upon the data and serve as a liaison with data-providing agencies. This service could be funded in a manner similar to CTSI’s existing consultation services (CTSI subsidy for initial hour of consultation, recharge for subsequent hours of service). It could also be made available to researchers at other CTSAs to broaden the potential user base.

Potential Partners: Members of Stanford’s CTSA have expressed interest in collaborating with UCSF CTSI to enhance capacity to conduct research using secondary datasets. CTSAs at other UC campuses may be interested as may faculty and trainees in the School of Public Health at UC-Berkeley. The UC Research Exchange would be a valuable partner in this effort due to its experience in bringing UC campuses together to improve access to administrative data for health research. In addition, CELDAC’s principal investigator has good contacts with staff of OSHPD’s Healthcare Information Division who are interested in enhancing their ability to serve researchers and other customers.

Innovation: This proposal builds upon UCSF CTSI’s existing resources for conducting research with large administrative datasets by creating a data concierge service that would help UCSF researchers to more quickly obtain secondary datasets tailored to their specific research interests. If successful, CELDAC could be transformed from a conduit of information about datasets that other organizations generate to a concierge that works proactively with these organizations to help researchers at UCSF and potentially other CTSAs obtain the data they need for their research. Making requisite public data more accessible is expected to significantly expand the use of secondary data to address important hypotheses in public health and comparative effectiveness research. This innovation may be particularly valuable during the current contraction in national research funding.

Projected Impact: This project could enhance UCSF researchers’ ability to conduct timely research using large administrative datasets that would enhance our understanding of factors that affect human health. If successful, the project could serve as a model for other CTSAs.

Commenting is closed.

Precision medicine approaches to diagnosis of neurodegenerative disease

Proposal Status: 

Once considered rare, neurodegenerative diseases are now recognized as among the most common and devastating health problems of aging. However, the clinical symptoms and brain imaging signs on which current diagnostic criteria are based still rely heavily on subjective clinical interpretation.  As a result, diagnosis is often made relatively late in the clinical course, and is often inaccurate, particularly in community settings.  Clinical trials for potentially disease-modifying treatments are proliferating, but these are targeted to specific neuropathologies such as a-beta, tau, and progranulin. Early and accurate diagnosis is thus essential to move appropriate patients into clinical trials at the earliest possible stage and to start specific, disease modifying treatment as early as possible.

A precision medicine approach to neurodegenerative disease requires that all levels of the patient’s clinical system be represented, maximizing clinicians’ ability to identify interactions among key features of the genetic, genomic, metabolic, brain, and cognitive profile to correctly predict and treat disease.  However, before such multilevel interactions can be understood in an individual patient, clinical researchers must first identify them in large, comprehensively characterized cohorts of patients.  International efforts such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) have paved the way by gathering not only structural and functional brain images, but also genes, biological specimens, and comprehensive clinical data on large cohorts of patients.  However, there is still a pressing need to build such multilevel datasets from cohorts of patients with other neurodegenerative diseases.  The rapid proliferation of studies using ADNI data proves that when such a resource is made openly available to the research community, there is an exponential increase in the speed of discovery, leading more quickly to precise disease characterization and diagnosis.


While open sharing of data from carefully characterized neurodegenerative disease cohorts is key to accelerating scientific discovery, a second essential element in a precision medicine approach to these diseases is to build mechanisms that bring these scientific refinements back to the community. Currently, though a clinician might obtain a structural MRI as a standard part of their diagnostic evaluation, they often do not possess the level of expertise to accurately interpret that scan. If clinicians anywhere were able to access an automated resource that incorporated the most refined diagnostic approaches available for interpreting their patients’ MRIs, it would substantially reduce the chance of misdiagnosis and immediately translate to substantial benefit for the patient and their family.


Aim 1:  We propose to create a national web-resource for automated quantitative analysis of structural brain MRIs, designed to provide diagnostic differentiation across neurodegenerative diseases. The technology already exists to perform automated analysis of regional atrophy from structural MRI scans. Voxel-based morphometry combined with automated diagnostic algorithms derived from support vector machine (SVM) learning approaches have been effective in differentiating patients with Alzheimer’s disease, progressive aphasia, and frontotemporal dementia.  We propose to enhance and pipeline this process by
1) refining the SVM algorithms for all of the most common neurodegenerative diseases, including cross-validating algorithm accuracy on additional samples
2) determining and testing the quality control parameters involved in evaluating MRI scans from scanners with varying acquisition protocols, and
3) programming an online system that would accept uploads of MRIs from any center, automatically inspect the images for quality issues influencing interpretation, and generate a report providing probabilities of pattern-matching to different diseases.
Our collaborators for this project will include Kaiser Permanente, a rich source for well-characterized elderly patients with MRI and genetic data, as well as imaging/visualization specialists at Lawrence Berkeley National Labs, who have agreed to collaborate on development of algorithms for both quality control and interpretation, and the UCSF Center for Imaging of Neurodegenerative Disease, the lead site for ADNI.


Aim 2:  We will create and archive a multilevel precision medicine dataset carefully describing all aspects of clinical presentation and biology in this valuable cohort of patients with various neurodegenerative diseases, which will be made available to the wider scientific community for download and analysis. In the process of constructing and validating this tool for automated MRI interpretation, we estimate we will need to expand our cohort to a total of 1,000 neurodegenerative disease patients and 500 healthy older controls. This creates a unique opportunity to establish and disseminate a dataset that describes these patients at every key biological level from gene to cognition, making it possible to approach the diagnosis and treatment of these diseases from a systems perspective.
1) Though we will already have these patients’ brain scans and clinical phenotyping, we propose to also systematically perform assays of the specimens already collected from these individuals to more fully characterize their genetic, genomic, and metabolic profiles.
2) We will fully document, quality check, deidentify, and homogenize the data so it can be effectively but securely downloaded and utilized by the scientific community.

Commenting is closed.

Grants program for collaborative, multidisciplinary, translational research

Proposal Status: 

We recommend that the UCSF CTSI initiate a grants program to support collaborative, multidisciplinary, translational research (CMTR) at UCSF and, in future years, across the entire UC system.

      1. Scale and significance of the problem. Successful translational research requires the collaborative effort of individuals with expertise in a broad range of disciplines, including (among many) bench science, structural biology, chemistry, clinical medicine, and statistics. At UCSF, as at almost all academic research centers, collaboration among faculty and trainees is made difficult by the mechanisms of funding, which reward individual success, and by the measures of academic success, which do not sufficiently reward collaboration. Despite this, there is a strong tradition of collegiality at UCSF and we believe that support for collaborative translational research here will be rewarded with success. This effort can then be scaled to include the other UC campuses, to broaden expertise and access to patients. This would be facilitated by current initiatives to foster collaborations across UC medical centers (e.g., BRAID and UC ReX).

      2. Current approaches (nationally). The NIH has stressed the importance of translational research and academic centers have moved to meet this need in a variety of ways. Often, these approaches are “top-down,” including, for example, the creation of new departments or facilities to create lead compounds or to develop screening procedures for drugs. UCSF has in addition utilized “bottom-up” approaches, supporting investigators with concepts that may lead to new therapies, e.g., the T1 Catalyst program and the UCSF/Pfizer Center for Therapeutic Innovation. The CTSI has in particular supported the development of clinical researchers, with notable success. These efforts, however, have not yet succeeded in developing strong partnerships between clinical and basic sciences. Instead, at UCSF, as at most academic medical centers across the nation, basic scientists and clinical scientists work in different worlds, with little overlap. We believe that the CTSI has the power to help change this.

      3. Proposed approach and why it is innovative. We propose that the CTSI directly counter the barriers to collaborative translational research by supporting research that promotes synergy among investigators across highly disparate areas of research. Collaboration between clinical and basic science investigators would be especially encouraged. Awards would be for up to $100,000, spent over a period of up to two years. Criteria would include:  A. Goals that will advance the possibility of new therapies or diagnostics that will benefit humans with disease. Translation of discoveries made in UCSF laboratories would be given high priority; B. An operational plan that demonstrates how support will promote interactions and collaboration among investigators; C. A path to clinical implementation, even if this is not a goal of the grant. D. Explanation of how the studies will add value to the work such that it is more likely to generate support from other sources.

Applicants would be encouraged to make use of the CTSI resources, e.g., in statistics, study design, patient recruitment, etc. Applications would begin with a one-page pre-application. Selected pre-applicants would be invited to submit a 4-page application for review by a standing committee. Full applications would be accepted at least twice yearly.

During the first two years of the CMTR program it would be limited to UCSF, in order to test approaches and maximize success. In the third year, the program would be expanded to include all UC campuses, thereby enhancing the breadth of expertise as well as the number patients studied. Other UC campuses would be asked to contribute to the costs of the collaborative programs.

Even as we provide support for collaborative, multidisciplinary research, we would initiate programs to facilitate this. Possible approaches include:  (1) a research “exchange”, where investigators can post ideas, problems, and requests and where they can ‘recruit’ collaborators – like a Craig’s list for research, (2) work with the sponsors of the proposed “speed dating” approach to linking investigators, (3) leverage Profiles to identify researchers working on areas of possible common interest, (4) create a small leadership team with broad knowledge of programs and individuals at UCSF to serve as “matchmakers” for collaborative research, (5) strive to enhance the culture of collaborative research at UCSF by altering promotion criteria to favor it, and by educating faculty in opportunities for collaborative research, (6) as suggested by the review panel, planning for the CMTR program would benefit from input by non-health care partners regarding methods for fostering cross-disciplinary research, e.g., Technology (Google, Microsoft) or Energy (Schlumberger, Chevron), etc.

By supporting collaboration rather than individual effort, the CMTR program will tap into the great expertise in both clinical and bench science at UCSF. The innovation in this approach is its direct support of a bridge between these domains. Support for team research has long been the approach in industry, but it is little tested in academia.

      4. Potential Partners. The proposed program will benefit from several CTSI programs that already exist, including especially the Catalyst Award and the Annual Pilot Awards.  Indeed these have overlapping aims with the CMTR program.  The CMTR differs substantially in its emphasis on cross-disciplinary research, but there may be opportunity to wed the Catalyst program and/or other CTSI programs to the proposed CMTR program.  The CTSI will also be of direct scientific benefit because of its relevant programs for consultation in statistics, patient recruitment, data management, etc. 

Within UCSF, we will be assisted by recent efforts to standardize and centralize biobanking and to access information in the biorepositories.  We plan to partner with other UC campuses beginning in year 3, and we expect that this will increase funding. For the review of applications, we will use not only UC faculty but also representatives from Pharma, as well as from non-health care partners on methods for fostering cross-disciplinary research as noted above. Pharma is also an expected future partner for successful awardees, and is even a potential partner for the CMTR program itself. Although we do not plan to use patients or disease advocates in reviewing grants, we do plan to use them in reviewing the success and failures of the program.

      5. Projected Impact. Translational research inherently carries high risk, with a concomitant high payoff if successful. Because of this, it is our expectation that many of the projects will fail. If they do not, we are probably not assuming enough risk. But the payoff can be very large, as shown by the UCSF Program for Breakthrough Biomedical Research (PIBBR), which supports risky research but has brought in support that is many times greater than the investment.

This proposal is endorsed by:  Joe DeRisi (Biochemistry and Biophysics), John Fahy (Medicine), Kathy Giacomini (BioEngineering and Therapeutic Sciences), Steve Hauser (Neurology), Tippi MacKenzie (Surgery), Mike McCune (Medicine), William Seaman (Medicine), Kevin Shannon (Pediatrics), Kevan Shokat (Cellular and Molecular Pharmacology), Eric Small (Medicine) and Zena Werb (Anatomy).



Supporting Documents: 

Commenting is closed.

Brain on Fire Network

Proposal Status: 

Problem: Rapidly progressive encephalopathies are diagnostically challenging and provide great potential for scientific and clinical advancement by harnessing the interdisciplinary resources and collaborative infrastructure of the CTSIs.We need systems to rapidly identify emerging infections and immunologically-mediated nervous system disorders and to investigate their causes and possible genetic contributors in order to provide rapid, efficient and cost-effective diagnosis, discover new diseases, and guide appropriate treatment.

A revolution has occurred in neurology and psychiatry with the identification of antibody-mediated neurological encephalopathies and psychiatric illness. A similar development has occurred in pathogen discovery with the use of high throughput techniques (many pioneered here at UCSF). As genome sequencing rapidly becomes more affordable, obtainable and powerful, it should provide new insights into the mechanisms and risk factors for these disorders spanning several medical disciplines.  

We propose to establish a “Brain on Fire” Network to actualize a vision of translational medicine by connecting the clinic to outstanding laboratory cores. The goal will be to create a pipeline for identifying whether patients with rapidly progressive encephalopathies or psychiatric disorders might have an infection or a primary immunological disorder, and if so, what are the genetic contributors. This network will link the clinic, research units, and high-throughput laboratory pipelines for pathogen discovery (requiring CTSI expertise/resources for coordinating, including engagement with research cores and appropriate public health labs, such as the CA Department of Health and the CDC), and CNS antibody discovery programs (utilizing CTSI expertise/resources to create and support national collaboration). This network will link investigators from a broad range of disciplines.

Antibodies against extracellular neuronal or other CNS cell antigens cause these syndromes. Unlike the known paraneoplastic antibody-associated syndromes, which were primarily due to intracellular antigens and were difficult to treat, these newer syndromes caused by antibodies against extracellular neuronal or other CNS cell antigens are readily treatable, even curable. They also are now at least five times more common than typical paraneoplastic antibody associated syndromes. The phenotypes often involve cognitive impairment, movement disorders, psychiatric disorders, seizures, or a combination of these symptoms. These disorders overlap multiple disciplines, including medicine (general, immunology, rheumatology, infectious disease), psychiatry, neurology and others. One common syndrome, which begins with psychiatric symptoms that progress to frank psychosis and then to violent movement disorders and pulmonary failure, is associated with antibodies to the N-methyl-D-aspartate receptor (NMDAR). For many years, these unfortunate patients were thought to have infectious encephalitis due to unidentified viruses; only with new immunological techniques and methods has the cause of these enigmatic disorders been identified. Other related disorders include voltage-gated potassium channel complex (VGKC encephalopathies), AMPAR encephalitis, GAD65 associated seizures, ataxia and/or encephalopathy. New syndromes are rapidly being discovered, making this one of the most exciting new areas of medicine.

Current approaches (nationally): Only a few centers in the world have the technical and clinical expertise to identify new syndromes and manage these patients. To our knowledge, only three laboratories in the world (Oxford, Mayo and Barcelona) are actively identifying novel antibodies and syndromes. Despite a few institutions working to identify these disorders, there is no consistent, multidisciplinary approach. As these syndromes are becoming more frequent, we need to develop a systematic network for surveillance, identification and study of these disorders.

Solution: Establish a network of centers with clinical expertise in identifying possible autoimmune mediated neurological, psychiatric, and “infectious” disorders. Asses and follow patients in a comprehensive, standardized, manner clinically, immunologically, radiologically, and genetically. Clinicians work closely with various CTSI basic science cores. Immunology cores will screen for known and novel antibodies and antigens. Genetic cores will assess various risk factors.

Potential partners: Various CTSIs, including our own, as well as Mayo and UPENN, already have some expertise in these areas. It would be important to train and incorporate other centers as well.

Projected impact: As these patients often require a long time for proper diagnosis, this system should greatly decrease the time to diagnosis and initiation of appropriate therapies and lead to significant cost savings to the medical system. Discovery of new diseases and disease mechanisms should have significant impact on public health, save millions of dollars annually and prevent unnecessary morbidity and death.

Commenting is closed.

Translating Neurobiological Knowledge into Psychosocial and Behavioral Interventions That can Prevent and Treat Stress-Related Illness

Proposal Status: 


 The Problem

               We live in a highly stressful world that has resulted in an unprecedented incidence of stress-related mental and physical illnesses. Research in the neurosciences has made significant progress in identifying the role of environmental stressors (e.g. violence, abuse, disasters, neglect, harassment, discrimination) in the development of illness. There is particularly striking evidence that one’s interpersonal environment can shape and modify neurobiological factors that subsequently result in health problems. There is also growing evidence to indicate the role of psychosocial and behavioral interventions in modifying these neurobiological factors. Yet little research has focused on translating this exciting knowledge into evidence-based interventions to prevent and treat adverse effects of stress on health.  Although highly relevant to adults, psychosocial/behavioral interventions for stress-related illness have particular importance for children whose brains and other organ systems are more vulnerable to adverse effects of biological treatments. In addition, early interventions with children have the potential to address emerging problems before they develop into more severe disease.  

Current Approaches

               The importance of stress reduction is widely recognized.  However, there is a significant gap between advances in the neurosciences regarding allostatic load, psychoneuroimmunology, or epigenetics and their application to the development and testing of psychosocial/behavioral interventions that can attenuate or modify the neurobiological effects of stress on the nervous system. Studies are needed to assess the impact of these interventions on neuroplasticity and to examine how neurobiological outcomes of these therapies relate to psychological and physical symptoms across stress-related disorders.

Proposed Approach

               The UCSF CTSI can create a targeted program that encourages the translation of basic neuroscientific knowledge into the development and testing of psychotherapeutic and behavioral interventions for stress-related illnesses. This would involve 2 key components: 1) develop a centralized infrastructure that will bring together investigators in the field to share their expertise and facilitate collaboration of researchers across stress-related health problems. This infrastructure could also include innovative subject recruitment programs, a sample repository specific to stress-related biomarkers, and a repertoire of interventions that show promise in enhancing therapeutic neuroplasticity and reducing stress-related neurobiological deficits or injury; and 2) provide funding for pilot studies to test psychosocial/behavioral interventions that build on neuroscientific findings and measure the impact of these interventions on biomarkers specific to these findings.

Potential Partners

               There are many opportunities for collaboration. One of our strong community partners - Children’s Hospital and Research Center in Oakland – is submitting this idea in collaboration with UCSF. There would also be interest from our partners at SF General Hospital, SF Child and Behavioral Health Services, and CHILD at UCB. On a national level, there could be collaboration with the National Network of Depression Centers (of which our UCSF Depression Center is a member) and their CTSIs/CTSAs. This initiative would have important links to many of our CTSI’s programs, including Recruitment and Study Management Services, Strategic Opportunities Support, Community Engagement and Health Policy, and Early Translational Research.

Projected Impact and Innovation

               The initiative will foster collaboration among different disciplines at UCSF, with our community partners, and with colleagues nationally to achieve a much greater impact than would the efforts of individual investigative teams. It could provide a model infrastructure for an innovative field of research that other CTSIs and research institutions could use to advance the prevention and treatment of stress-related illnesses. It will also provide support to interdisciplinary, investigative teams in conducting important pilot work that will serve as the basis for applications to acquire extramural funding.  The initiative is highly congruent with NIH interests in fostering multi-disciplinary and biobehavioral research.   




Commenting is closed.

Minimizing the CTSA carbon footprint

Proposal Status: 

How can we minimize our contributions to global warming in the operation of our CTSI and CTSA programs in general? An example of a high carbon activity are airplane flights. Are there ways to use alternative communication modalities to avoid taking more transcontinental flights than necessary for scientific meetings, administrative activities, etc? The challenge of this big tent proposal would be to perform an inventory of our CTSI carbon footprint and find ways to reduce it without compromising our programs.

Commenting is closed.

Open data

Proposal Status: 

Academic institutions, civic agencies at all levels, and NGOs of all kinds have joined what’s being called a “data revolution” by making the information they collect and use publicly available. How can this “open data” movement advance and accelerate clinical and translational research to improve health and eliminate health inequities? The CTSI Open Data Initiative will bring together under one umbrella projects currently underway at UCSF and other UC campuses along with their government and community partners to explore fruitful routes and best practices for maximizing the applicability and interoperability of publicly available (and potentially available) datasets, including clinical and population health data; economic and demographic data; transportation and planning data; and research datasets that could influence and improve the health care and health status of individuals and populations. 

Activities at UCSF that fall under the rubric of this initiative include SFHIP (including HUMS), CELDAC, and DataShare. Partners in San Francisco include the Hospital Council of Northern and Central California, SF Department of Public Health, DataSF/Mayor’s Office of Civic Innovation, SF Police Department, SF MTA, SF Rec and Park Department, District Attorney’s Office, and other city offices and agencies. Community partners include the San Francisco health disparities and health parity coalitions, healthy retail coalitions, alcohol prevention coalition, and nonprofits such as the YMCA. Resources would support the application and use of open data to meet the aims and activities of those health improvement and disparities-focused partnerships. Resources would also support the development of evidence-based health and healthcare apps and other technology tools (registries, health information exchanges, new and improved mobile devices). Activities would include Translational Science Hackathons and intensive workshops to identify mutually-held incentives, establish cost-savings goals, and activate assets and resources to maximize the impact of collaborative efforts.

Commenting is closed.


Proposal Status: 

Osteoporosis is a highly prevalent disorder in older postmenopausal women both nationally and internationally, and a potent major risk factor for subsequent fracture.  Among older women of white race, it is estimated that approximately 1 in 2 women will experience an osteoporotic fracture in her lifetime. Nationwide efforts during the past two decades have led to evidence-based consensus guidelines for osteoporosis screening and treatment, with the goal of both primary and secondary fracture risk reduction. Models to assess fracture risk integrating a number of independent clinical risk factors have also been developed to support clinical therapeutic decisions, including web-based applications.  Beyond pharmacologic therapy, the importance of falls prevention, patient and family education, and modification of lifestyle factors and/or the home environment have been increasingly recognized. Given the projected increase in the U.S. population aged 65 years and older during the next two decades, there is a critical need to develop interdisciplinary programs and research methodology that focus on comprehensive risk assessment, including markers of bone fragility, nutritional status and novel methods for assessing functional status and risk of falls, in the context of osteoporosis care. 

This proposal will bring together expertise in endocrinology, geriatric medicine, nutrition, physical therapy and epidemiology/biostatistics and focus on the development of a large prospective cohort of older community-dwelling individuals across diverse health settings and communities (e.g. UCSF, Kaiser, SFGH, VAMC and other new Bay Area partners in geriatric care) and integrate existing data available in the electronic health record, newly collected data elements and novel interventions with the overall goal of maximizing the net clinical benefit of fracture prevention strategies in both white and non-white populations.  The proposed initiative would facilitate innovative approaches to improving individual-level risk assessment, enhance our understanding of the factors driving disparities across various patient subgroups, and create a population-level resource to support new efforts in fracture risk reduction and quality improvement strategies. 

Commenting is closed.