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Systemic physiological state profoundly influences cancer progression, metastatic relapse, and therapeutic response. The Gomes Laboratory aims to define the metabolic and epigenetic vulnerabilities that emerge during metastasis and to understand how host physiology influences metastatic progression, dormancy, and relapse. A major focus of the laboratory is understanding how distinct chromatin remodeling dictates and metabolic programs support different stages of metastatic progression, including dissemination, long-term dormancy, metastatic awakening, and therapy resistance. By uncovering how systemic physiology and epigenetic and metabolic adaptation shape cancer cell fitness and plasticity, we aim to identify therapeutic strategies capable of suppressing metastasis, preventing relapse, and improving patient outcomes.
Cancer progression and metastasis are accompanied by profound metabolic rewiring that enables tumor cells to adapt to constantly changing microenvironmental pressures. The Gomes Laboratory investigates how distinct metabolic programs support different stages of the metastatic cascade, including dissemination, dormancy, metastatic awakening, and therapeutic resistance. Our work has identified key metabolic pathways that promote aggressive cancer cell behavior, including age-associated metabolites such as methylmalonic acid (MMA) and redox-regulating pathways such as NAD kinase (NADK), which enhance metastatic fitness and cellular adaptation during the metastatic cascade. A major current focus of our laboratory is understanding the metabolic requirements of dormant disseminated tumor cells, a clinically important but poorly understood cell state that can persist silently within distant organs for years before reactivating to drive metastatic relapse. We are particularly interested in defining how dormant cancer cells regulate redox balance, nutrient utilization, and survival pathways to withstand the nutrient-limited and stressful metastatic niches. By understanding how metabolism shapes cancer cell plasticity, metastatic competence, and therapeutic resistance across the different stages of the metastatic cascade, we aim to uncover metabolic vulnerabilities that can be therapeutically targeted to suppress metastasis and prevent cancer relapse.
Metabolic Regulation of Metastatic Progression
Tumors actively reshape systemic physiology through metabolic competition, inflammatory signaling, and the secretion of tumor-derived factors that influence distant organs and whole-body homeostasis. The Gomes Laboratory investigates how tumor-driven metabolic alterations impact host physiology during cancer progression and survivorship, with a particular interest in understanding how these systemic changes influence patient health decline and life after remission. A major focus of our work is understanding how host metabolic state and tumor-derived metabolic programs contribute to cachexia and systemic tissue dysfunction. We are interested in defining how tumors alter nutrient utilization, mitochondrial function, inflammatory signaling, and inter-organ communication to drive muscle wasting, metabolic imbalance, and progressive physiological decline during advanced disease. In addition, we investigate how tumor-induced metabolic and inflammatory changes influence brain function and neural physiology. Our laboratory is particularly interested in understanding how circulating metabolites, cytokines, and tumor-associated metabolic stress alter neuronal signaling, cognition, neuroinflammation, and neuro-immune communication during cancer progression and metastasis. By defining how tumors reshape systemic metabolism and host physiology, we aim to uncover mechanisms linking cancer progression to whole-body dysfunction and identify therapeutic opportunities capable of improving both cancer outcomes and quality of life for patients.
Tumor-Host Metabolic Communication
Our laboratory has previously uncovered fundamental roles for the histone variant H3.3 in regulating cancer cell identity and metastatic dissemination as well as survival of circulating cancer cells. A major current focus of the laboratory is understanding the role of H3.3 in dormant disseminated cancer cells, a clinically important but poorly understood population capable of surviving silently within distant organs for years before reactivating to drive metastatic relapse. We investigate how H3.3-dependent chromatin states regulate dormancy maintenance, survival within metastatic niches, and the transition toward aggressive metastatic outgrowth. Building on these findings, we also investigate how H3.3 deposition and chromatin remodeling function as adaptive sensing mechanisms that integrate environmental and host-derived signals to control cancer cell fate during progression and metastasis. By defining how epigenetic sensing mechanisms control cancer cell state transitions in response to host-derived signals, we aim to uncover new therapeutic opportunities to suppress metastasis and prevent cancer relapse.
Epigenetic Regulation of Metastatic Cell States
Diet and systemic metabolic state profoundly influence cancer progression, metastatic relapse, and therapeutic response. The Gomes Laboratory investigates how nutrient availability, obesity-associated metabolic alterations, and circulating host-derived factors shape cancer cell behavior across distinct stages of metastatic progression. Our work focuses on understanding how systemic metabolism influences metastatic fitness, dormancy regulation, and organ-specific metastatic colonization. A major area of interest in the laboratory is understanding how metabolic state regulates dormant disseminated cancer cells. We investigate how dietary and metabolic cues influence nutrient utilization, metabolic networks, redox balance, and stress-adaptation pathways that support dormant cell survival and metastatic awakening. We are also interested in how systemic metabolism influences metastatic tissue tropism and the ability of cancer cells to adapt to the unique metabolic environments of different organs. By defining how host metabolic state reshapes metastatic niches and cancer cell metabolism, we aim to uncover therapeutic strategies capable of suppressing metastatic progression, preventing relapse, and improving long-term patient outcomes.
Diet, Obesity, and Cancer Relapse
What metabolic vulnerabilities emerge during metastatic progression?
How does host metabolic state influence metastatic organotropism and relapse?
How do epigenetic programs regulate metastatic competence and dormancy?
Questions We Are Interested In:
Can diet regulate dormant cancer cell behavior?
How do tumors reshape systemic physiology?
Can host physiology and epigenetic regulation be therapeutically targeted to prevent relapse?
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