The Damon Runyon Cancer Research Foundation has announced eight recipients of the 2024 Damon Runyon-Rachleff Innovation Award, established to support “high-risk, high-reward” ideas with the potential to significantly impact the prevention, diagnosis, or treatment of cancer. Five extraordinary early-career researchers will receive initial grants of $400,000 over two years, and each will have the opportunity to receive two additional years of funding (for a potential total of $800,000). This year, this “Stage 2” continuation support was granted to three current Innovators who demonstrated significant progress on their proposed research during the first two years of the award.
The Innovation Award is designed to provide funding to exceptionally creative thinkers with a revolutionary idea who lack sufficient preliminary data to obtain traditional funding. The awardees are selected through a highly competitive and rigorous process by a scientific committee comprised of leading cancer researchers with their own history of innovative work.
Previous Damon Runyon-Rachleff Innovators have pioneered the development of CAR T-cell therapies, revolutionized the biomedical sciences with CRISPR gene editing tools and single-cell sequencing methods, and developed computational methods for analyzing large datasets that continue to yield lifesaving discoveries.
This program was established thanks to the generosity of Andy and Debbie Rachleff.
New 2024 Damon Runyon-Rachleff Innovators
Alex M. Jaeger, PhD, H. Lee Moffitt Cancer Center & Research Institute
William Raveis Charitable Fund Innovator
"Engineering approaches to exploit MHC-II antigen presentation in cancer"
Recent advances in genomic and proteomic technologies have ushered in a new era of antigen-specific immunotherapies, including cancer vaccines. Such therapies depend upon immune system recognition and processing of antigens—proteins or fragments of proteins displayed on the cancer cell surface. However, our understanding of the principles that govern antigen presentation across cell types throughout the tumor microenvironment (TME) remains limited. Dr. Jaeger’s research uses sophisticated mouse models to understand how cells present and process antigens in healthy lung tissue and the lung cancer TME. These studies will advance our understanding of how different patterns of antigen presentation activate different T cell pathways and identify opportunities to engineer next-generation immunotherapies. The fundamental insights gained from these studies will be broadly applicable to multiple cancer types.
Daniel J. Puleston, PhD, Icahn School of Medicine at Mount Sinai
“A new platform to study cancer biology and therapy in humans”
The exploration of human tumors in their native environment is challenging, precluding a deeper understanding of how cancer and important therapeutics work. Dr. Puleston is developing new ways to investigate human cancer by keeping tumor-bearing organs alive outside of the body, allowing for the experimental study of tumors within human tissues. Employing this approach to study hepatocellular carcinoma (HCC), one of the most lethal forms of liver cancer, Dr. Puleston will expose HCC-laden livers to immunotherapy drugs and metabolic tracers to reveal the metabolic landscape of HCC cancers and how tumor metabolism is shaped following drug treatment. Through the study of tumors and anti-cancer agents in situ, Dr. Puleston hopes to elucidate new pathways with therapeutic potential and novel strategies to optimize existing therapeutics.
Sydney M. Shaffer, MD, PhD, University of Pennsylvania
“Spatially resolved cellular competition in oncogenesis”
Normal tissues naturally weed out harmful cells to prevent cancer. But when cancer develops, this defense system breaks down, allowing the cancer to attack healthy cells for its own growth. The Shaffer lab is set to explore this process, called cell competition, in esophageal cancer. By employing precise tracking and advanced spatial analysis, Dr. Shaffer aims to reveal how cell competition contributes to cancer development and how it might be harnessed to prevent it. The goal of her research is to pioneer early intervention therapies to halt cancer in its tracks.
Humsa S. Venkatesh, PhD, Brigham and Women's Hospital
“Identifying and disrupting the bioelectric circuits driving brain cancer”
Brain cancers are one of the most common causes of cancer-related death and represent 120 molecularly distinct diseases. Despite advances in clarifying the genetic landscape of these cancers, they remain clinically intractable, underscoring the need to elucidate the complex factors contributing to their heterogeneity. As neuronal activity is known to govern the development of neural circuits and neuroplasticity, it is critical to consider these neural networks in the context of disease. Dr. Venkatesh will use classical and systems neuroscience approaches to determine how the nervous system contributes to brain cancer progression. A comprehensive understanding of malignant neural network interactions may lead to novel therapeutic interventions aimed at normalizing the tumor microenvironment.
Ziyang Zhang, PhD, University of California, Berkeley
“Small molecule activators of GTP hydrolysis for mutant Ras-driven cancer”
Cancer growth is often driven by the dysregulation of a class of proteins known as small GTPases. These proteins act as molecular “on/off” switches that regulate critical cellular processes such as cell division and movement. However, in cancer, these molecular switches often become stuck in the “on” state due to mutations that hamper GTP hydrolysis, the reaction that turns “off” the GTPase switch. One notable example is the family of GTPases encoded by Ras genes, which are mutated in 30% of all human cancers. Dr. Zhang’s research aims to design small molecules that inactivate these mutant GTPases by accelerating GTP hydrolysis. His research will provide a new therapeutic mechanism for the treatment of mutant Ras-driven cancer for which no direct therapies are yet available. The design principles may also apply to the modulation of other small GTPases whose overactivation underlies cancer progression.
2024 Stage 2 Damon Runyon-Rachleff Innovators
Nora Kory, PhD, Harvard T.H. Chan School of Public Health
“Targeting mitochondrial transporters in cancer”
Cancer cells rely on efficient uptake, conversion, and exchange of nutrients and vitamins to support their rapid growth and survival. The molecular transport channels that allow passage of nutrients between the different cellular compartments are critical for the survival of cancer cells and are thus promising as potential drug targets. However, drug discovery efforts are hampered by a lack of basic understanding of these channels' identities, functions, and regulation inside cancer cells. Dr. Kory's research aims to identify transporters central to cancer cell nutrient supply and detoxification pathways and determine their role in the emergence, survival, and aggressiveness of cancer. Her research is relevant to all cancers, but particularly pediatric, blood, and breast cancers.
Jamie B. Spangler, PhD, Johns Hopkins University
“Engineered multispecific antibody-drug conjugates as novel cancer immunotherapeutics”
Groundbreaking advances in immunotherapy have revolutionized the treatment of cancer. In particular, new antibody drugs that block immunosuppressive pathways have achieved remarkable success in reawakening the immune system to clear tumor cells, leading to lasting cures in patients whose cancers do not respond to any other therapies. Unfortunately, the majority of patients (>70%) do not respond to immunotherapy treatment. It is difficult to predict which patients will benefit, creating an urgent demand for novel immunotherapy drugs that act through alternative mechanisms. Dr. Spangler is working to develop a class of antibody therapeutics that target cancer-promoting pathways in a different way than all current immunotherapies, with the goal of drastically expanding the percentage of cancer patients who benefit from them.
Srinivas R. Viswanathan, MD, PhD, Dana-Farber Cancer Institute
“X marks the spot: exploring how X-chromosome alterations drive sex differences in cancer”
Epidemiologic studies have revealed that many cancer types display differences in incidence or outcomes between the sexes. In most cases, these differences are only partially explained by non-genetic factors such as hormonal differences, carcinogen exposure, lifestyle, and access to health care. Our understanding of how genetic factors contribute to differences in cancer incidence between the sexes remains incomplete. A fundamental genetic difference between the sexes is in chromosome composition. Relative to male somatic cells, female somatic cells have an extra X chromosome. Most genes on the second copy of chromosome X in females are inactivated via a process known as X-chromosome inactivation, which approximately equalizes the dosage of X-linked genes between males and females. Dr. Viswanathan's project tests the hypothesis that genetic alterations to the X chromosome in cancer may perturb this carefully regulated process and thereby contribute to differences in cancer incidence or pathogenic mechanisms between males and females.
