The Damon Runyon Cancer Research Foundation has announced ten recipients of the 2022 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 initial grants of $400,000 over two years have been awarded to six extraordinary early-career researchers (four individuals and one collaborative team), each of whom will have the opportunity to receive two additional years of funding (for a total of $800,000). This year, “Stage 2” continuation support was granted to four 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. Only those scientists with a clear vision and passion for curing cancer are selected to receive the prestigious award.
Examples of past accomplishments made by Damon Runyon-Rachleff Innovators include the development of the gene editing technology CRISPR and single-cell sequencing techniques that have revolutionized not only cancer research but biomedical sciences globally.
This program was established thanks to the generosity of Andy and Debbie Rachleff.
New 2022 Damon Runyon-Rachleff Innovators
Chengcheng Jin, PhD, University of Pennsylvania
"Investigating neuro-immune interaction in lung cancer"
Dr. Jin’s research focuses on the interaction between the nervous system and the immune system in cancer, with a particular focus on the crosstalk between the sensory neurons and the tumor microenvironment (TME) in lung cancer. While nerves have long been viewed as passive bystanders in cancer, solid tumors are innervated by distinct branches of the nervous system that respond to internal and environmental stimuli. However, it remains poorly understood how the nervous system regulates tumor-associated immune cells, and what factors in the TME shape tumor innervation and neuro-immune interactions. Dr. Jin will combine genetically engineered mouse models with diverse approaches in cellular immunology, cancer genetics, and functional manipulations of neuronal circuits to elucidate the molecular and cellular mechanism of neuro-immune crosstalk in the lung TME, and to explore how we can target specific neural pathways to improve cancer immunotherapy.
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 down-regulating antibodies to advance cancer immunotherapy”
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.
Ekaterina V. Vinogradova, PhD, The Rockefeller University, and Santosha A. Vardhana, MD, PhD, Memorial Sloan Kettering Cancer Center
“Investigating and targeting T cell exhaustion in solid tumors”
Non-small cell lung cancer (NSCLC) is the most widely diagnosed type of lung cancer. Together with mesothelioma (cancer associated with asbestos exposure), NSCLC can result in the formation of malignant pleural effusions (MPE)—a build-up of fluids and cancer cells between the chest wall and the lung. The MPE tumor microenvironment is known to negatively affect immune T cell proliferation and function, resulting in failure of current immunotherapies and low median survival rates. Dr. Vinogradova and Dr. Vardhana are using robust in vitro and in vivo models of T cell dysfunction to understand the molecular mechanisms by which the lung tumor microenvironment suppresses anti-tumor T cell responses, with the goal of developing novel strategies to restore T cell function in these high-risk patients.
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.
2022 Stage 2 Damon Runyon-Rachleff Innovators
Michael E. Birnbaum, PhD, Massachusetts Institute of Technology
“Decoding and reprogramming tumor-infiltrating T cells by pMHC-targeted lentiviruses”
Immunotherapies that rely on reinvigorating T cells to patrol the body, detect cancerous cells, and eliminate them have shown the potential for long-lasting cures. Despite their initial success, however, immunotherapies have been effective only for some cancers and for some patients. To improve outcomes, Dr. Birnbaum has developed a new method to match T cells with their antigen targets on cancer cells by engineering viruses to use T cell recognition as a means of cell entry. This technology will be applicable to a wide range of cancers, including ones for which immunotherapy is not currently effective.
Brian B. Liau, PhD, Harvard University
“Investigating allosteric mechanisms regulating DNA methyltransferase enzymes”
DNA methyltransferase enzymes, responsible for adding methyl groups to DNA strands, are critical for controlling gene expression. These enzymes are often disrupted in cancers, including acute myeloid leukemia (AML), but their regulation is not understood. One form of enzyme regulation, called allostery, involves a regulator molecule binding to an enzyme at a site other than its active site. Dr. Liau is pioneering approaches to explore allostery, specifically focusing on allosteric mechanisms that regulate DNA methyltransferase function. His research will shed light on the impact of cancer mutations on enzyme function and strategies to pharmacologically modulate their activity. The approaches developed will be broadly expanded to study other enzymes disrupted in cancer and leveraged with synthetic chemistry to enable therapeutics discovery.
Michael E. Pacold, MD, PhD, NYU Langone Health
“Tracing molecular oxygen in pancreatic cancer”
Oxygen is a double-edged sword in pancreatic cancer biology. Pancreatic cancers require oxygen, but they are amongst the most hypoxic of cancers, with oxygen concentrations as low as 200-fold below atmospheric oxygen concentrations. Pancreatic cancers use oxygen to make molecules critical for their survival and proliferation, but they are also vulnerable to oxidative stress, which is essential for the effectiveness of cancer treatments such as radiation. Dr. Pacold has developed techniques to determine which oxygen-dependent reactions are prioritized by pancreatic cancers and enhanced by radiation treatment, with the goal of identifying new targets that can be used for pancreatic and other cancers that are treated with radiation.
Elli Papaemmanuil, PhD, Memorial Sloan Kettering Cancer Center
“Leveraging multi-modal genome profiling approaches to study disease initiation, progression, and response to therapy in TP53-mutated myeloid neoplasms”
Cancer survivors are at a higher risk of developing blood cancers than the general population due to the toxic effects of cancer treatments. Therapy-related blood cancers are often resistant to existing drugs and therefore extremely challenging to treat. Contrary to previous thought, recent studies show that the mutations causing these blood cancers can be identified in patients' blood many years before they receive therapy. Dr. Papaemmanuil has discovered that the existing mutations alone are not sufficient to cause therapy-related cancer but require the acquisition of additional mutations that affect large segments of the DNA, or "allelic imbalances." She will pursue further studies to screen patients and understand the mechanisms of therapy-related blood cancers. These findings will inform clinical strategies of early detection and targeted intervention to better treat this aggressive disease.
