‘Think Big’: 2019 Michelson Prize Winners on How the Award Advanced Their High-Risk/High-Reward Research
Dr. Avinash Das Sahu (Dana-Farber Cancer Institute), Dr. Kamal Mandal (University of California, San Francisco), and Dr. Murad Mamedov (Stanford University) share how the Michelson Prizes: Next Generation Grants advanced their research projects for vaccine immunology and immunotherapy in 2019.
One of the unexpected benefits from the Michelson Prizes has been new collaborations between researchers who otherwise wouldn’t have known each other. Like the burgeoning partnership between two scientists who won the 2018 prize, two new winners began collaborating after meeting at the 2019 award ceremony.
The Michelson Prizes: Next Generation grants, awarded by the Michelson Medical Research Foundation (MMRF) and the Human Immunome Project,(formerly the Human Vaccines Project) give $150,000 annually to investigators 35 or younger who are advancing the study of human immunology, vaccine discovery, and immunotherapy.
Previous winners of the prize also said the funds and prestige from receiving the prize have been instrumental in advancing their groundbreaking research at the dawn of their careers.
Now Michelson Philanthropies, MMRF, and the Human Vaccines Project are gearing up to announce the new winners of the Michelson Prizes for 2021 on January 25, 2022.
Read about the 2019 winners below, Dr. Murad Mamedov, Dr. Kamal Mandal, and Dr. Avinash Das Sahu, who share their discoveries and their career trajectories and also offer advice to investigators thinking about applying. The prize allowed them to pursue projects they were passionate about, helped grow their teams, and gave them needed independence.
Read about the 2018 winners here, and check back in the coming days for stories about the 2020 Michelson Prizes winners.
Dr. Murad Mamedov
Dr. Mamedov received the Michelson Prize for Human Immunology and Vaccine Research in 2019 for: “Mapping Gamma Delta (γδ) T Cell Receptor Ligands.”
Dr. Mamedov uses gene-editing technologies to create a new platform for understanding an important set of immune cells that may provide the keys to the diagnosis, prevention, and treatment of infectious and non-communicable diseases such as cancer.
While pursuing his Ph.D. in immunology from Stanford University, Dr. Mamedov became interested in a rare immune subset called γδ T cells, which he studied in a malaria model, because they are not well understood but have a lot of therapeutic promise both in infectious disease and cancer immunology settings.
He wanted to find a lab where he could learn new skills and apply them to γδ T cells, so he went to the Marson Lab at the Gladstone-UCSF Institute of Genomic Immunology, which specializes in using genome-wide screens or smaller pooled CRISPR screens to identify various regulation of T cell activity. These tools can be used both for discovery and for therapeutic design. In Dr. Mamedov’s case, he ended up focusing on using CRISPR screens and various CRISPR tools to understand how γδ T cells recognize and kill cancer cells.
That’s what he proposed for the Michelson Prize, because it’s a clear case of a high-risk/high-reward project that would probably have a difficult time getting conventional funding otherwise but would yield a lot of useful information if someone could get the technology he was proposing to work.
“What I proposed was using these novel tools to look throughout the genome for regulators of their activity, which doesn’t really lend itself to the narrow, hypothesis-driven, reductionist approach that is often conducive to getting an NIH grant, for example,” he explained. “So this was the perfect marriage of what the Michelson Prize was looking for and what we were trying to do: trying to break open the gamma-delta field and understand how gamma-deltas do what they do.”
“Think big. Hit that sweet spot between being very ambitious but also making it somewhat doable. Make it exciting and address some problem that really gets you excited. Marry that with doing good science.”
—Dr. Murad Mamedov
He said receiving the prize was great timing because since then he has been able to hire a talented technician straight out of undergrad and train them for the various experiments that are part of his project. This has enabled him to go much faster because there are two people conducting experiments. And while the Marson Lab is well-funded, he added that it was still helpful to know that he had his own funding which allowed him to be more independent, as he is the only one who studies γδ T cells in the lab.
Dr. Mamedov also connected with one of the other researchers who won the Michelson Prize the same year, Dr. Avinash Das Sahu. After they met at the symposium where they were awarded the prize, they discovered Dr. Sahu’s project had developed tools that were very useful to what Dr. Mamedov was studying.
“Dr. Sahu ended up doing a bunch of analysis that enriched our paper and that I would have not been able to do on my own, because he has a very specialized skill set,” Dr. Mamedov said. “Right now, we’re finishing up my paper, he will be one of the co-authors, and we’re submitting it very soon.”
Dr. Mamedov had some words of advice for any early-career researcher who is thinking about applying for the Michelson Prize. The 2022 application opens April 1.
“Think big,” he said, “because we’re not always encouraged to, not so much by our mentors, who want us to think big, but just by the constraints of normal funding mechanisms. I always tell people to think big and to try and hit that sweet spot between being very ambitious but also making it somewhat doable. It can’t be too outlandish. Make it exciting and address some problem that is really on your mind a lot, that really gets you excited, because that comes out on the page, versus something that’s forced, that you’re just trying to fit into the mold that you think is there for you to fill. That excitement and ambition really comes through and it’s hard to fake. But also obviously marrying that with doing good science, which includes being realistic and understanding the literature and what’s already out there and having all the right controls. And so really hitting that sweet spot I think is the key.”
Learn more about Dr. Mamedov’s project here and his work here.
Dr. Kamal Mandal
Dr. Mandal received the Michelson Prize for Human Immunology and Vaccine Research in 2019 for: “‘Structural Surfaceomics’: An Approach to Identify Cancer Specific Cell Surface Protein Conformations for Immunotherapeutic Targeting.”
Dr. Mandal is developing new technologies that identify the shape of proteins that could provide new targets for cancer immunotherapy, with potential applications to other diseases.
“Immunotherapy is a pretty powerful technology, an umbrella of techniques that basically trick the immune system to make it do a better job that it otherwise wouldn’t do,” Dr. Mandal said. “For example, you get cancer when the immune system fails to respond against it efficiently. We have now enough knowledge about the immune system to be able to trick it to act efficiently against cancer. But it’s pretty hard to distinguish between the cancer cells and the normal cells.”
He explained that typically in the field of cancer immunotherapy or cancer therapeutics, scientists look for some proteins which are present on the surface of cancer cells and not on the normal cells to be able to establish a therapeutic design to kill those cells that display a particular protein. However, unlike infectious agents, like bacteria or viruses, that have a completely different set of surface proteins, cancer cells are not that different from healthy cells, making it difficult to distinguish diseased from normal. This presented a challenge.
“We wanted to make it more precise and leave the normal cells untouched, which would make it less toxic and be safer,” he said. “We wanted to go a step further and develop therapies against those surface proteins, or antigens, on cancer cells which have a different 3D shape than those on normal cells. We developed a new technology called structural surfaceomics, which profiles the cell surface proteins of cancer cells so we can take a knowledge-based approach to interrogate their 3D structure for immunotherapeutic targeting. We combined two different technologies to develop it: cross-linking mass spectrometry coupled with cell surface enrichment proteomics.”
Other funding agencies considered this project too risky at its early stages, but the Michelson Prize’s forward-thinking approach enabled this science to happen.
Dr. Mandal said he and his team believe it can be used to address not just cancer, but any other kind of disease as well. For proof of concept, they applied it on acute myeloid leukemia (AML) and successfully identified one confirmation-based target. He said they’re not allowed to reveal the target right now, only that it is working well so far.
“At this point, the data I have is that it does kill the cancer cells, the AML cells, and it doesn’t touch any of the normal cells,” he said, adding that they’re still conducting rigorous validation. His goal is to continue developing this therapy and ultimately reach clinical trials for patients with AML, who currently have limited therapeutic options.
Dr. Mandal said winning the Michelson Prize helped advance his research immensely. The prize provided the funding and support to acquire critical data to show the promise of his approach as well as validate the first proof-of-principle therapeutic target. Other funding agencies considered this project too risky at those early stages, but the Michelson Prize’s forward-thinking approach enabled this science to happen. The promising data obtained under the Michelson Prize has now allowed Dr. Mandal to obtain follow-on funding from the National Institutes of Health, to further move this technology forward in development.
For those early-career researchers considering whether to apply for the Michelson Prize, Dr. Mandal said the idea “has to be beyond the horizon. If it’s within the horizon, you can’t make it to the Michelson Prize. It has to be beyond the horizon. It should look infeasible with the currently available methodologies.”
The 2022 application opens April 1.
Learn more about Dr. Mandal’s project here and his work here.
Dr. Avinash Das Sahu
Dr. Sahu received the Michelson Prize for Human Immunology and Vaccine Research in 2019 for: “Identification of Cancer Drugs that Boost Immunotherapy Response.”
Dr. Sahu is building novel artificial-intelligence (AI) deep-learning frameworks to devise new therapeutic strategies for cancer immunotherapy, with potential applications in human immunology. He has focused on how to incorporate a computational approach that can complement existing experimental therapies.
That project led to the development of a new class of drug which has two ways to kill cancer, through direct and indirect methods, such as activating the immune system. Dr. Sahu said winning the Michelson Prize helped to fund not only his high-risk/high-reward project and a new research/computational scientist he hired, but also to develop a tool that could experimentally validate the findings of the project.
“It came at a really critical moment, where it really helped us to think bigger,” he said. “Now, not only do we focus on finding this immunotherapy, but we found a whole class of drugs. The prize allowed me to do that.”
Now Dr. Sahu and his team are developing a plan on how they can not only identify drugs, but also identify the cancer patients who can benefit from those drugs. They are looking at how to match effective drugs with a very specific patient, which will allow them to design informed clinical trials.
“The seed money which I got from the Michelson Prize led to all this award and discovery, which I think are quite critical, and hopefully it could have an impact in cancer immunology.”
—Dr. Avinash Das Sahu
“That’s the new direction my lab will be taking, to go towards precision immuno-oncology, the term which I’m using to define not only identifying drugs, but also finding the target population and designing clinical trials to test those combinations,” he said.
After winning the Michelson Prize, Dr. Sahu then refined the preliminary data that he originally generated, eventually leading to a K99 award from NCI, known as the Pathway to Independence award. He was also included in a list of the top 40 emerging cancer immunologists in the United States by the Irvine Family Foundation.
“The seed money which I got from the Michelson Prize led to all this award and discovery, which I think are quite critical, and hopefully it could have an impact in cancer immunology,” he said.
As for advice for future early-career scientists who are thinking about applying for the Michelson Prize, Dr. Sahu said an innovative idea is key.
“As opposed to other grant applications, specifically for an NIH grant, where you need cancer preliminary data and to really develop the plan—you almost have to finish several projects before you write the grant so as to mitigate the risks involved with the grant—the Michelson Prize is focused on the innovative part of it,” he said. “It’s more about the idea itself. What is the innovation, what is the impact, and not so much on the preliminary research. So many people have such good ideas. Rather than trying to generate preliminary results and putting those into the grant, it’s about how to focus on the innovation and impact of the grant. That really helped.”
Stay tuned for an announcement about the 2021 Michelson Prize award winners on January 25! Learn more about the Michelson Prizes here.