The Damon Runyon Foundation for Cancer Research has named five new Damon Runyon Clinical Investigators. Recipients of this prestigious award are outstanding early-career physician-scientists who conduct patient-focused cancer research at leading research centers under the mentorship of the nation’s top scientists and clinicians.
The Clinical Investigator Fellowship program was designed to help address the shortage of physicians capable of translating scientific discoveries into new breakthroughs for cancer patients. Each winner will receive $600,000 over three years, as well as assistance with research costs such as the purchase of equipment. Since the need to repay medical school loans is often cited as a barrier to pursuing research, Damon Runyon will also repay up to $100,000 of medical school debt owed by the fellow.
The Foundation also awarded continuation grants to three Damon Runyon clinical investigators for two additional years of funding, totaling $400,000 each. Continuation grants are designed to support clinical investigators who are nearing the end of their initial award and need more time to work on a promising line of research or clinical trial. This program is made possible through the generous support of the William K. Bowes, Jr. Foundation.
“The quality of research delivered by our clinical investigators is exceptionally strong. We are thrilled to fund courageous and daring physician-scientists who take risks to experimentally answer the most important questions in cancer research and then translate them into improving the lives of patients,” said Yung S. Lie, PhD, President and CEO of Damon Runyon. “We’re helping launch the careers of tomorrow’s brightest cancer researchers.”
Through partnerships with generous donors, industry sponsors, and its Accelerating Cancer Cures initiative, the Damon Runyon Cancer Research Foundation has committed more than $80 million to support the careers of 119 physician-scientists across the United States. United since 2000.
2022 Clinical Researchers
Daniel J. Delitto, MD, PhD, with mentor Michael T. Longaker, MD, DSc, at Stanford University, Stanford
Pancreatic cancer develops amid intense scarring and fibrous connective tissue (fibrosis). The architects of this scarring are cells called fibroblasts, which are known to fuel cancer growth and promote resistance to treatment. Dr. Delitto’s research focuses on the interface between cancer-induced fibrosis and the immune system. He showed that fibroblasts play an important role in protecting cancer cells against immune cells. By altering the way fibroblasts sense tissue damage, Dr. Delitto discovered a mechanism that reactivates the immune system to fight the tumor. He aims to further develop these findings into a novel immunotherapy regimen for pancreatic cancer.
Xiuning Le, MD, PhD, with mentor John V. Heymach, MD, PhD, at the University of Texas MD Anderson Cancer Center, Houston
Mutations in the EGFR were identified as the first targetable mutations in lung cancer about two decades ago. Since then, multiple targeted therapies have been approved and have extended many lives. However, about 15% of EGFR the mutations are atypical and have no currently approved targeted therapy. Dr. Le is leading several clinical trials to address this unmet need. With the potential arrival of new treatments in the clinic, new mechanisms of treatment resistance are likely to evolve. Dr. Le aims to comprehensively characterize resistance mechanisms and compare the susceptibility to resistance in different types of EGFR– related lung cancers. She will use state-of-the-art techniques to determine mutations at the single-cell level and develop rational therapeutic strategies to overcome resistance. This project has the potential to not only bring new FDA-approved treatments to patients, but also establish clinical strategies to predict and target key resistance mechanisms.
Nathan Singh, MD [Bakewell Foundation Clinical Investigator]with mentor John F. DiPersio, MD, PhD, at Washington University, St. Louis
Chimeric antigen receptor T cell (CAR T cell) therapy, in which a patient’s own immune cells are engineered to target their cancer, has changed the treatment landscape for many blood cancers. Despite promising early results, however, long-term follow-up has revealed that nearly half of patients treated with CAR T cells eventually experience cancer recurrence. Using a variety of techniques in cell lines and patient samples, Dr. Singh aims to understand how interactions between engineered T cells and blood cancer cells lead in some cases to long-term remission and in others. others to treatment failure. The overall goals of his lab are to understand the biological signals that cause these therapies to fail and to use this knowledge to design next-generation immunotherapies that can cure more patients.
Melody Smith, MD, with mentor Robert S. Negrin, MD, at Stanford University, Stanford
The microorganisms that live in the digestive tract, also known as the gut microbiome, have become important factors in patient response to cancer treatment. Studies have shown that the gut microbiome can modulate the anti-tumor immune response to several types of therapy, including chimeric antigen receptor T cell (CAR T cell) therapy, in which the d a patient are genetically engineered to target their cancer. CAR T therapy has led to unprecedented responses in patients with high-risk blood cancers such as leukemia and lymphoma. However, patients may experience disease relapse or CAR-mediated toxicities. Dr. Smith found that responses to CAR T therapy are linked to alterations and abundance of the gut microbiome. His research will focus on how the gut microbiome mediates this impact on CAR T cells. skills needed to become physician-researchers.
Aaron D. Viny, MD [Damon Runyon-Doris Duke Clinical Investigator]with mentors Emmanuelle Passegué, PhD, and Joseph G. Jurcic, MD, at Columbia University, New York
Up to 50% of patients with acute myeloid leukemia (AML) have a genetic alteration called DNA methylation, in which a carbon methyl group is added to the DNA molecule, which usually turns off the methylated gene. A mainstay of therapy is the use of hypomethylating agents, which prevent these changes from being copied during cell division, but this therapy is only effective in 20-30% of patients. Using chemical and genetic manipulations in mouse bone marrow, Dr. Viny aims to determine the effect of DNA methylation on the ability of specific regions of the genome to be accessible to proteins involved in the expression genes and other regions to be inaccessible and ‘silenced’. In a prospective Phase II clinical trial, it will treat patients with relapsed AML with dual hypomethylating agents. By studying the genetic profiles of these patients, he aims to determine the genetic characteristics that contribute to therapeutic response, thereby paving the way for the development of more effective interventions for patients with acute myeloid leukemia. Dr. Viny was previously a Damon Runyon Scholar.
Beneficiaries of the 2022 continuation
Jennifer M. Kalish, MD, PhD, with mentors Marisa S. Bartolomei, PhD, and Garrett M. Brodeur, MD, at Children’s Hospital of Philadelphia, Philadelphia
Dr. Kalish studies a rare inherited syndrome called Beckwith-Wiedemann Syndrome (BWS), which increases the risk of children developing kidney and liver cancers. These people have epigenetic changes on chromosome 11 that are found in other types of cancers. Epigenetic markers modify DNA so that gene expression is turned on or off; changes in this process can cause cancer. By understanding how cancer is triggered in BWS, Dr. Kalish aims to identify pathways that can be targeted for the development of new treatments for both patients with BWS and other people with cancers who present with similar epigenetic changes. As a physician-scientist, Dr. Kalish created the BWS Registry, which compiles both clinical data and patient samples, and created the first human cell models of BWS.
Matthew G. Oser, MD, PhD, with mentor William G. Kaelin, Jr., MD, at Dana-Farber Cancer Institute, Boston
Although small cell lung cancer (SCLC) is initially very responsive to chemotherapy, the disease recurs in almost all patients within a year. There are currently no approved targeted therapies for cancer return. Previous studies have demonstrated that SCLCs require sustained neuroendocrine differentiation to survive, suggesting that targeting this process might be a good therapeutic strategy. Dr. Oser will use xenograft models derived from SCLC patients and a new genetically engineered SCLC mouse model to identify novel enzymes required for neuroendocrine differentiation and to develop targeted therapies that can block this process. It aims to identify molecular targets that could be developed into new sustainable therapies for SCLC patients.
Kavita Y. Sarin, MD, Ph.D. [D.G. ‘Mitch’ Mitchell Clinical Investigator]with mentors Jean Y. Tang, MD, PhD, and Anthony E. Oro, MD, PhD, at Stanford University, Stanford
Basal cell cancer (BCC) is the most common cancer in the United States, with 2 million cases per year, resulting in a social cost of $5 billion. Although the majority of BCCs are small and surgically accessible, some people develop frequent recurrences of BCCs and experience severe surgery-related disability and decreased quality of life. Dr. Sarin will focus on a group of 100 patients who develop extreme numbers of this skin lesion, to identify the genetic mechanisms that contribute to cancer susceptibility. While most BCCs are thought to develop from DNA damage caused by the sun’s ultraviolet rays, a patient’s genetics also play a vital role in the progression of the disease. Understanding the mechanisms that contribute to cancer susceptibility will help identify those at risk so they can be monitored for earlier diagnosis and prevention. It also aims to develop new non-surgical therapies for these patients.
Damon Runyon Foundation for Cancer Research