The oncogene c-MYC is a “master regulator” that drives aggressive cancer growth but is widely considered “undruggable” due to its lack of an accessible drug-binding pocket. Inside a cell, the levels of c-MYC protein are tightly controlled at both the RNA and protein levels by various chemical modifications. For example, c-MYC messenger RNA (mRNA) is frequently modified with the addition of a methyl group, which typically triggers rapid mRNA decay. Dr. Su and his colleagues recently discovered that c-MYC mRNA can also be decorated with two methyl groups, a completely new class of modification. Crucial questions remain unanswered: What is the biological impact of this modification on c-MYC? Which enzyme installs it? How does it alter c-MYC function? Dr. Su will address these questions using multidisciplinary approaches, revealing a fundamentally new mechanism of c-MYC regulation and paving the way for novel therapeutics designed to interfere with c-MYC modifications in cancer cells. Dr. Su received his PhD from the University of Georgia, Athens, and his BS from Zhejiang University, Hangzhou.

Normal cells convert glucose into energy via cellular respiration in the mitochondria, but cancer cells often rely on alternative metabolic pathways that support rapid growth. Central to this strategy is the pyruvate dehydrogenase complex, an enzymatic switch that controls how cells use glucose. Dr. McMinimy studies a newly discovered pathway that regulates this switch through selective protein degradation. By understanding and manipulating this pathway, she hopes to redirect cancer cell metabolism back toward the mitochondria, potentially slowing tumor growth. Dr. McMinimy received her PhD from the University of California, Berkeley, and her BA from Oberlin College, Oberlin.

Only two percent of the human genome contains instructions for making proteins. Much of the remaining 98 percent, once referred to as “genomic dark matter,” consists of regulatory elements that act as molecular switches to turn genes on or off. These molecular switches are broadly categorized into two groups: enhancers (on-switches) and silencers (off-switches). While it is well-known that cancers exploit enhancer elements to amplify the expression of growth-promoting genes, silencers remain poorly understood. Dr. Aboreden’s research focuses on the repressive mechanisms that cancer cells use to sustain uncontrolled growth. He is mapping the regulatory genome of an aggressive type of pediatric leukemia characterized by widespread gene repression. By identifying silencer elements that these cancer cells use to maintain a malignant state, his work aims to identify new therapeutic vulnerabilities to selectively target cancer. The insights gleaned from this work will have broad relevance across diverse tumor types. Dr. Aboreden received his PhD from the University of Pennsylvania, Philadelphia, his MS from Johns Hopkins University, Baltimore, and his BS from Liberty University, Lynchburg.

Even within the same tumor, cancer cells can differ in which genes they turn on or off, allowing some cells to adapt, survive treatment, or become more aggressive. These differences are often driven by changes in the epigenome, a layer of regulation that controls gene activity. Dr. Wang’s project explores the origin of epigenetic heterogeneity in cancer, focusing on the role of genome instability in driving epigenetic changes. By identifying the genes and pathways that connect these processes, she aims to better understand how cancer cells generate and maintain epigenetic heterogeneity, revealing new ways to limit tumor evolution, adaptation, and treatment resistance across all cancer types. Dr. Wang received her PhD from the University of California, Los Angeles, and her BS from Emory University, Decatur.

Changes in appetite and metabolism can affect how tumors develop, how they progress, and overall patient prognosis. Peptide hormones are small signaling molecules that help organs communicate and coordinate whole-body metabolism. Recent computational studies suggest that the brain may produce many more peptides than previously recognized—yet for most of these, we still do not know what they do, where they act, or how they work together. Dr. Li aims to identify new peptide signals produced by the brain and determine how they affect appetite and regulate metabolism. This work may reveal new brain-body signaling pathways that could ultimately help support cancer treatment and improve patient well-being. Dr. Li received her PhD from Stanford University, Stanford, and her BS from Peking University, Beijing.  

More than half of all FDA-approved biotherapeutics target proteins on the cell surface involved in intercellular communication. The vast majority of these proteins are decorated with post-translational modifications (PTMs), such as the addition of a sugar molecule, but our understanding of how individual PTMs affect communication in a disease context is poor. As aggressive tumors often have surface proteins thickly coated in sugar molecules, they are suspected to play a role in in driving oncogenic growth and tumor immune evasion. Dr. Muthukumar will map cell surface and intracellular membrane PTMs in cancer cells, and then interrogate the role each of these PTMs play in oncogenesis with precise mutational genomic screens. This will highlight the PTMs that drive tumor pathology, allowing for the development of new precision therapeutics and cancer diagnostic markers. Dr. Muthukumar received her PhD from the Massachusetts Institute of Technology, Cambridge, and her BA from Columbia University, New York.

During mitosis, two copies of the genome condense and segregate, a process catalyzed by a protein known as transcription termination factor 2 (TTF2). Mutations in TTF2 have been associated with incomplete genome segregation, DNA damage, and cell death. Research has shown that TTF2 is necessary for many cancers, making it a prime target for future cancer therapeutics. Dr. Pistofidis aims to use a combination of structural biology, biochemistry, and single-molecule biophysics to outline the molecular mechanism of TTF2. Ultimately, this work will reveal vulnerabilities in the mechanism of TTF2 that can be exploited for the development of cancer therapeutics. Dr. Pistofidis received his PhD from McGill University, Montréal, and his MSc from the University College London, London.

Cell surface proteins play prominent roles in regulating immune responses and govern intercellular communications within the tumor microenvironment. To study the roles of cell surface proteins during cancer progression at exceptional molecular resolution, Dr. Hua aims to develop SortID, a novel labeling technology based on an engineered bacterial enzyme. SortID will be able to rapidly label any exposed protein residues on the cell surface, enabling precise mapping of the cell surface without pre-installed tags. To demonstrate its transformative utility, Dr. Hua will deploy SortID to map the surface of SLAMF7, a critical therapeutic target in multiple myeloma. Ultimately, SortID will provide a highly precise and comprehensive map of cell surface interactions, deepening our understanding of cancer progression and unlocking novel targets for targeted immunotherapies. Dr. Hua received his PhD from Princeton University, Princeton, and his BS from Tsinghua University, Beijing. 

Dr. Ferreira seeks to explore dietary, microbial, and metabolic strategies to treat immune-related colitis (ir-colitis), one of the most common autoimmune toxicities resulting from immunotherapy treatment. Ir-colitis results when the patient’s immune system becomes overstimulated after immunotherapy and attacks the colon, leading to diarrhea and other gastrointestinal symptoms that can result in discontinuation of potentially life-saving immunotherapy. Although ir-colitis can be treated with steroids and other immunosuppressive agents, it remains unclear whether this immunosuppression may affect treatment. Targeting the gut microbiome through dietary intervention is a promising strategy to treat ir-colitis without interfering with cancer treatment. She plans to use a mouse model of ir-colitis to study whether intermittent fasting can be used to treat ir-colitis while simultaneously improving tumor control. She will investigate the specific metabolic and gut microbial changes that are responsible for fasting’s effects on ir-colitis, with the goal of expanding non-immunosuppressive and accessible treatment options for this common immunotherapy toxicity.

Dr. Kuthyar studies why cancer patients, especially those receiving treatments like chemotherapy or radiation, are at high risk of developing serious lung infections such as pneumonia. While these treatments are essential for killing cancer cells, they also weaken a key part of the immune system that normally helps the body detect and eliminate bacteria. This weakened defense makes patients more vulnerable to infection. At the same time, many hospitalized patients receive supplemental oxygen, which can change the lung environment in ways that help certain bacteria grow stronger and become more aggressive. In cancer patients, these two factors are closely connected: the weakened immune system cannot effectively control bacteria, while the high-oxygen environment actively promotes bacterial survival and virulence. Together, this creates a perfect storm that increases both the risk of contracting pneumonia and severity of disease. This work is relevant to cancers commonly treated with immune-suppressing therapies, including leukemia, lymphoma, and solid tumors such as lung, breast, and colorectal cancer, and aims to identify better ways to predict, prevent, and treat these life-threatening infections.

This project proposes a framework to dissect pneumonia risk in immunocompromised patients using human and mouse models. Dr. Kuthyar will use hierarchical networks to link gene expression and metabolites. Multi-omics factor analysis will capture microbial and immune variation and models trained on human data will be tested in mice, enabling iterative prediction and validation. This approach integrates species harmonization, metabolite prioritization, and network mapping to reveal hyperoxia-driven microbial adaptation and myeloid immune deficits driving pneumonia risk.