Tam Lab

Research Summary:

At the Tam Laboratory, we use functional genomics to understand how cancer cells rewire their metabolism and shift their identities to resist treatment and spread. Cancer progression is driven by complex changes in both gene function and cellular behavior. To survive, cancer cells constantly adapt—shifting between states like stemness and differentiation, or transitioning from localized tumors to metastatic phenotypes. These cellular adaptations directly drive disease progression and patient outcomes. To tackle this, we team up with clinician partners to uncover exactly how these cancer cell states are controlled. By mapping out these mechanisms and targeting specific metabolic pathways, our goal is to develop selective therapies that overcome drug resistance and stop metastasis in its tracks. Our lab takes a highly multidisciplinary approach to solve these challenges. We combine cutting-edge tools—spanning genomics, transcriptomics, computational biology, and metabolomics—with high-throughput chemical screens, whole-genome engineering, biophysics, and organoid models. Ultimately, we aim to translate these complex biological discoveries into real-world clinical interventions.

Cancer cell states:

For cancer to metastasize and resist treatment, cells must undergo critical shifts in their identity, a process known as phenotypic plasticity. We investigate how cancer cells rewire their molecular, biochemical, and physical pathways to adapt and thrive during disease progression. By manipulating the pathways that govern these cell states, we aim to uncover new therapeutic interventions that can fundamentally alter the course of the disease. 

Cancer metabolism:

Cancer is fundamentally a metabolic disease. While Otto Warburg first noticed cancer cells' intense hunger for glucose back in the 1920s, we now know this "Warburg effect" is just the tip of the iceberg. As tumors grow and spread, they undergo a massive and complex rewiring of their entire metabolism. Our research investigates these unique metabolic adaptations. We focus on how these shifts control flexible cancer cell states and drive metabolic crosstalk within the tumor microenvironment. Because tumors are highly diverse, a major goal for our lab is decoding exactly how different phenotypic cell states lead to distinct metabolic changes. As cancer cells transition between states to survive and progress, their changing metabolism offers a unique therapeutic window. As highlighted in our recent findings below, disrupting these specific metabolic processes gives us a powerful way to target vulnerable cell states and prevent tumors from acquiring aggressive, hard-to-treat phenotypes.

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Niche Biology and Tumor Microenvironment:

While cancer cells can fuel themselves, they do not grow in isolation. They are constantly interacting with the tumor microenvironment (TME), and we are just beginning to understand how tumor cells and surrounding stromal cells swap nutrients to survive. For example, fibroblasts often produce lactate as a byproduct, which neighboring carcinoma cells can scavenge and use as energy to fuel their own growth. However, this metabolic crosstalk presents a unique opportunity. What if the nutrients secreted by the microenvironment actually trap cancer cells into a "metabolic addiction"? Exploring how these external factors create targetable vulnerabilities in tumor cells is a major, unexplored frontier for our lab. By mapping out these metabolic conversations between the tumor and its niche, we aim to uncover new therapeutic blind spots. Ultimately, understanding these exchanges will help us design better therapies and reveal how the microenvironment impacts immune cell function and immune-oncometabolism.

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