Gretchen Kiser, PhD, executive director of the UCSF Research Development Office (RDO) shares on the origins and progress of this unique intramural funding program.

The Beginning 

Keith Yamamoto (vice chancellor for the Office for Science Policy and Strategy; director, UCSF Precision Medicine) used to hold meetings with Michael Faber (former associate vice chancellor, University Development and Alumni Relations), me and precision medicine related people. We thought it would be great to have a pot of money to encourage researchers to do bold things. Resource Allocation Program (RAP) grants are often smaller and more like an NIH grant – not necessarily encouraging scientists to be bold. Keith had this notion of a basic science underpinning to an idea with clear impacts to patients and society. We could understand the precision medicine continuum on a project but wanted to show its direct connections between many areas. The continuum is not just basic science to clinical medicine, but it’s also policy, implementation, and population health as described on the precision medicine website.

The Marcus Program in Precision Medicine Innovation (MPPMI) brings this notion to life with a connection between two types of thinking. For example, between a computational health scientist and a clinical researcher; a basic scientist with an implementation scientist. These are people that don’t necessarily talk to each other about their work all the time. However, discussion between them can lead to new hypotheses and ideas from either side.

We thought it would be great to get new funding to support us pursuing started that line of thought. Michael Faber had been in discussion with George and Judy Marcus along with Keith. They would support a pilot for two years with a $2 million commitment to focus on precision medicine innovation, using our broad definition of precision medicine.

High Risk, High Reward

The first mechanisms were the “Seeding Bold Ideas” (SBI) and a translational research grant, “Transformative Integrated Research” (TIR). Our thinking was to seed one-off, bold ideas since it’s harder for scientists to find this type of funding. The $300k grant per project could move it in a substantive way to get a project accomplished and potentially result in a publication.

Keith pushed for a concise application requirement with a short two-page idea pitch and description. These projects are supposed to be ‘high risk, high reward’ so we also accept that some of these ideas may not work. The research enterprise can often be risk averse, but Marcus program entities must be willing to try something that may not succeed. However, the ones that work make a big leap instead of just a simple step towards a scientific direction.

Ethical, Legal and Social Implication (ELSI)

Barbara Koenig, PhD, was part of our precision medicine team and created the Bioethics Program at UCSF. Koenig pointed out that some projects may not go far for various ethical reasons. For example, a research project cannot share genomic data since some policies inhibit that, like when you give genetic information to an individual.

There are programs now focused on whether we can act on these findings, especially on the genomics front. The ‘ethical, legal and social implications’ of projects we were funding in precision medicine had been missing a piece that made them viable relative to their impact.

We initiated the ELSI mechanism for this purpose to help with this missing piece of the precision medicine continuum. For example, how insurance impacts whether we can implement something. This type of funding is hard to find in NIH; it’s an unmet need in science funding. We have funded a lot of excellent projects that have investigated issues and brought forward data to address them.

Inclusion, Diversity, Equity, and Anti-Racism (IDEA) in Precision Medicine

In a social science sense, we later initiated the Inclusion, Diversity, Equity and Anti-Racism (IDEA) grant mechanisms. There were areas blocking our ability to be successful in the other types of research that we do relative to impacting real people. We realized we need computational expertise to address many issues like how to use data from underrepresented groups. We based the IDEA grant on this niche to do our research differently relative to the analysis methods, computational, retrospectively, and develop methods to have conclusions using computational methodology. For example, can we retrospectively look back at a study and the data that wasn’t used and now enable it to have some conclusions relative to some of these other populations?

The Anti-Racism research grants offered through the Resource Allocation Program are different. They focus on increasing diversity and inclusion in grants which have more to do with the inclusion of certain populations like through a better consent process. The focus of the IDEA grant comes from a different place - it’s on the execution of the research.

Making Ideas Fly

Our RDO and Precision Medicine leadership let us be ‘grassroots bold’ to try things out with a smaller amount of money to get a project going and later show its feasibility and value. That’s how all these mechanisms have been started and perpetuated.

The IDEA, ELSI, TIR, and SBI projects have been quite successful. It shows that there was a huge need and passionate yearning to do these projects that funding did not exist to support. Someone can have an anecdotal observation for several years and after being awarded from their two-page Marcus application they get to follow up on it.

The success of the Marcus program is its whole approach to information. For example, we shouldn’t throw precious data out, we should collaborate with the best computer scientists to figure out how to include the data in analyses. It brings huge value to a campus like UCSF with multiple geographic sites when this mix of people with different expertise and ways of thinking are brought together to tackle problems. The Marcus symposium also gives an opportunity to have interesting discussions that we typically don’t get when meeting in departments where everybody might have a similar background.

Almost every Marcus Award has led to a publication. The bold ideas are founded in a scientifically sound way. Projects we fund also lead to extramural funding of the preliminary knowledge that’s been developed from these projects. Marcus awardees have had spinoffs for outside companies and bolstered their venture capital gravitas on data that they got from their Marcus grants. 

Programs like this operating at about $2 million a year, which can be seen as a relatively small investment, can have a large impact and value in traditional research productivity measures and follow-on activities. Marcus funding has enabled an institution like UCSF to remain at the leading edge of innovation, new approaches, and bold thinking.

Awardee Perspectives - Past and Present

Jeroen Roose, PhD, professor, vice chair of Anatomy (2018 Transformative Integrated Research Awardee - “Tailored, Real-­time Models of Rare Driver Mutations in Human Cancer”)

“Will this therapy work for my cancer?” is the question that every cancer patient will ask their clinician. What if we could safely test many therapies on patient tumors in a dish, in the lab, so that better-informed therapy choices can be made?

Early support from the Marcus Program in Precision Medicine Innovation enabled the Roose lab to embrace a groundbreaking technology called “Organoids” that allows for patient-specific research. 

For 2 reasons, I believe organoids will have an incredible impact on biomedical research and human health in the near future. First, the cancer cells in the organoid from one patient look very much like the cancer cells in the body of that patient. So, organoids are like mini-patient avatars. Second, we can freeze and thaw patient organoids and our organoid efforts have already generated a large collection of these mini-patient avatars so that we can compare therapies but also patients against each other in a safe but faithful system that embraces the fact that every patient is unique.

Typical for the Marcus Program, they supported our vision early on. I expect that patient-specific organoid technology will have a very positive impact on Precision Medicine at UCSF and I see the technology as an ideal connector between research and clinical care at UCSF.”

Tony Capra, PhD, professor, Epidemiology and Biostatistics (2024 Transformative Integrated Research Awardee with Aleksander Rajkovic, PhD, MD  - “Beyond single variants: embracing genomic context and diversity in rare disease genome interpretation”)
 
“The Marcus Program is enabling my group to establish collaborations with clinical colleagues and demonstrate the power of our new artificial intelligence approaches to provide precision diagnoses. It is a critical step to ensuring that cutting-edge AI methods work beyond the lab and produce clinical benefits.

The Marcus Program appealed to me due to its focus on collaboration and innovation. The program's support frees us to take risks and try out bold ideas that would be challenging to fund via more conservative funding mechanisms."

See All Marcus Program in Precision Medicine 2024 Awards Projects

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RDO Spotlight: Gretchen Kiser, Evolution of the Research Development Office