Cohort Grant

All UCSF faculty members with a primary appointment in the Department of Medicine at any site are eligible to apply. Special consideration will be given to new or junior investigators with mentors who have relevant experience in the design, creation, and/or maintenance of patient cohorts.

Factors to be considered in the evaluation of proposals ranked in order of importance include:

1. Assistant or Associate Professor as of July 1, 2025 (offer letter required if appointment not yet official);
2. The opportunity for use of the cohort by other DOM or non-DOM investigators;
3. The prospect for sustained funding of the cohort;
4. The clinical importance and scientific value of the cohort;
5. The expertise to develop a cohort;
6. The feasibility of the plan for cohort development or expansion/improvement;
7. The significance/approach of scientific aim(s) that uses the new cohort;
8. Justified sample size for defined outcome for scientific aim(s);
9. Plan for follow-up to measure defined outcome(s);
10. Proper collection and storage of data and specimens and;
11. The qualifications of the investigators and, for new and junior faculty, of the mentor;
12. Contribution of cohort grant to advance applicant’s career.

There is no letter of intent for this round. Full applications (maximum 3 pages) are due Wednesday, April 30, 2025, 5:00PM PST, and shall be submitted via online form. A PDF attachment of all required documents should be attached via the online application form. If you have questions, please send them to Danielle Mizuiri, at [email protected].

The complete PDF with application materials shall contain:

1. Biosketch. For the applicant and, when applicable, for the mentor, submit an NIH biosketch https://grants.nih.gov/grants-process/write-application/forms-directory/biosketch. As with NIH applications, applicants should use Section A (Personal Statement) to briefly describe why their experience and qualifications make them particularly well suited for their role in the project.

2. Abstract (<250 words on one page). The abstract should summarize the main goals, the importance of the proposed work, the plan for developing a new cohort or for improving the use of an existing cohort, and the departments or organized research units involved.

3. Background, Need, and Specific Aims (~1 page). Why is this an important proposal? What are the new programs that are being developed? What is the context (e.g. other cohorts of similar patients non-existent) and what makes this proposed cohort unique in terms of patient population, predictors measured and/or outcome/s evaluated? What are the opportunities for this patient cohort to make advances that will improve our understanding of the pathophysiology of disease or otherwise produce benefits for patient outcomes? How will others use the cohort? How can support from this grant leverage current support or lead to new support?

4. Methods and Plans (~2 pages. The total number of pages for this section combined with “Background, Need and Specific Aims” should not exceed 3 pages.) What do you propose to do? Aim 1 should describe either the development of a new cohort or the enhancement of existing cohort. Describe the patient population, including selection criteria and number of patients to be enrolled per year. Document the method for estimating patient availability and willingness to participate. What patient populations will be involved? Aim 2 should describe a scientific aim that will use the new or unique measurements that will be collected in the cohort. How will these measurements be developed and standardized and (if appropriate) validated? What biological specimens will be stored? What is the projected sample size for the defined outcome and what is the statistical power for the projected aim(s)? How will information and samples from the patient cohort be made available to other investigators? How will the success of the cohort be measured? For new or junior faculty, what role will the mentor play? Describe milestones in the development and/or use of the cohort.

5. References (<1 page).

6. Proposed budget and budget justification. Use the NIH "Form Page 4" (detailed budget period) at http://grants.nih.gov/grants/funding/phs398/phs398.html. A separate page may be used for budget justification and to list other sources of support (direct costs only). Plans for future grant support should be under Methods and Plans.  Funds are not to be used for space, biological assays, equipment, or data analysis. Justify all personnel effort, PI and other faculty co-investigators not to exceed 10% effort. Any expenses for travel or consultants should be carefully justified for the unique value that they would add to the development of the cohort. Evidence of support, intent to support, or interest in supporting this cohort from outside sources would be advantageous.

7. Mentor's Support Letter. New or junior investigators should include a one-page letter of support from their mentor describing the experience and resources that will be provided to the applicant to help guide the direction of the proposed research. The letter should also describe how the project would, if funded, help the applicant transition from a mentored award to independent support. The letter also should describe contingency plans for ongoing cohort development should the applicant not be able to complete the two-year grant.

8. Other letters (maximum of 3). Letters from important collaborators may be appended to the application. To document the potential use of cohorts by other investigators, the application may include letters from investigators documenting their planned use of the cohort.

Edward Hsiao, MD, PhD, professor of endocrinology and metabolism at UCSF Health and director of the UCSF Metabolic Bone Clinic, provides his insights into how the Cohort Grant has impacted his research and career.

In 2017, DOM awarded you a Cohort Grant titled Longitudinal Expansion of the Biospecimens and Skeletal Tissues for Rare and Orphan Disease Genetics (BSTROnG) Metabolic Bone Disease Cohort. Tell us about your patient cohort. What was the focus, and what did you learn?  

Our initial cohort started small — focusing primarily on an ultra rare disease called fibrodysplasia ossificans progressiva (FOP), a 1 in 1.4 million congenital disease characterized by severe and progressive bone formation in skeletal muscles, ligaments and tendon. The Cohort grant allowed us to expand the spectrum of samples that we could collect and include FOP patients and autopsy samples from around the country, as well as from patients with other rare genetic diseases that we were seeing in the Metabolic Bone Clinic that we started in the Endocrine Division.

These human samples are incredibly valuable. Patients with rare diseases are often few and must travel long distances, and so being able to collect multiple patients with the same disorder in the same biobank really strengthens our studies. In addition, this biobank supported a number of collaborations within UCSF and with outside investigators, and in all sorts of different fields. For example, some of the samples we collected allowed us to explore how the gene that causes the prolific bone formation in FOP (ACVR1) also has critical roles in other tissues like the heart and peripheral nervous system. These have driven new discoveries and have allowed us to rethink the role of the gene in FOP and other diseases.

How did the Cohort Grant contribute to your research grant portfolio and scientific publications?

The grant provided direct support for growing our biospecimen collection — now the second or third largest collection for FOP samples in the USA. In addition, it has supported NIH grants, foundation grants, and internal grants by showing we have an established protocol/method for collecting specimens. Likewise, it supports our publications by being a central repository for unusual disease presentations. We have had some trainees use the samples for case reports and case series. The samples also support the translational aspects of grants and papers — allowing us to link human specimens and data to findings from animal and cell models that are discovered in the lab.

How has the cohort facilitated collaborations across disciplines and translational science?

Although I had originally envisioned the cohort as looking at rare bone disease patients, we quickly realized that these patients often have a lot of other disease manifestations in non-bone organs that people haven't studied. The cohort allowed us to identify collaborators in other fields — surgery, anesthesia, microbiome, for example — to start studying these new roles. In addition, the cohort has supported novel approaches to studying diseases — for example, by providing access to key human bone specimens in a mosaic disease for single cell RNA sequencing, and to support the generation of patient derived iPS cells. This has positioned our group and collaborators to be able to have storis that go full circle — allowing patient samples and clinical observations to drive the wet lab research using animal and stem cell models, to dissecting the molecular mechanisms of disease, to proposing novel therapeutic approaches. In addition, it has allowed us to collect clinical data to drive novel understanding of patients with rare conditions. Finally, we've now taken it a step further, and included SFGH and the SFVMC in our cohort — which will allow us to strengthen the biobank even more!

 What would you like to say to faculty considering applying for the Cohort Grant?

The cohort grant mechanism is a very forward-looking vision by the DOM. These cohorts are an incredibly valuable resource for many investigators, especially new investigators seeking to build a novel direction. It also brings a lot of meaning to the patients who contribute to it.  In addition, it positions UCSF and the DOM as leaders in translational research.  If this is what motivates you — being able to link human specimens and data to further clinical and basic research —this cohort development mechanism is for you!!