Genome Institute of Singapore, A*STAR
Cancer Science Institute of Singapore, National University of Singapore
Department of Biochemistry, National University of Singapore
School of Biological Sciences, Nanyang Technological University
Laboratory of Translational Cancer Biology
Research Summary:
Cancer progression is orchestrated by complex alterations in cellular behaviors that enable the survival of, and colonization by, cancer cells in the human body. Disturbances in cell states underlie disease progression and clinical outcomes. Underpinning the control of cancer cell states are metabolic reprogramming events, i.e., why are the nutritional needs of cancer cells unique or different? Many fundamental cancer pathways are now known to impinge on cell metabolism, and strategies focusing on disrupting specific metabolic processes to control disease progression have gained considerable interests. Leveraging on functional genomic approaches, and in close collaboration with clinician partners, our group seeks to gain insights into the precise control of cancer cell states, and specific targeting of metabolic pathways, for the development of selective therapeutics against cancer resistance and metastasis.
Cancer cell states:
The ability of cancer cells to metastasize and acquire resistance necessitates critical shifts in cell states, i.e. phenotypic plasticity. How do cancer cells rewire molecular, biochemical and phenotypic pathways for adapting to malignant progression?
By manipulating pathways regulating cell states, we aim to define therapeutic interventions that may alter the course of disease outcomes.
Cancer metabolism:
Over the decades, rapidly proliferating cancer cells have been shown to be dependent on the use of glucose as a source of energy. However, tumor inter- and intra-heterogeneity have revealed that distinct subtypes and subpopulations may require unique metabolites.
How is metabolic plasticity regulated in cancer in a context-dependent manner, and what are the avenues to exploit metabolic addiction as novel therapies?
RESEARCH THEMES
METABOLISM
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What are the metabolites produced and utilized by CSCs?
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Why are they uniquely important?
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How do we exploit the metabolic liabilities of CSCs as therapeutic targets?
CELL STATE PLASTICITY
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Can we rewire stemness and differentiation programs in cancer cells?
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What is the spectrum of the epithelial-mesenchymal transition? How do we control it?
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How to cancer cells reprogram for colonization?
TUMOR NICHE
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What are the interactions between cancer/CSCs and their cognate stromal?
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How can we develop niche-targeting therapies with patient-derived models?