ISSUE 2
Can we target cell metabolism to treat cancer (and other diseases)?
Spotlight on Kivanç Birsoy, the Chapman Perelman Associate Professor and head of the Laboratory of Metabolic Regulation and Genetics
When we think of metabolism, we often think on the scale of the whole organism: converting food into energy to fuel the body and mind. That macro-level metabolism is driven by countless complex chemical reactions occurring in our cells and known collectively as cellular metabolism.
Rockefeller’s Kivanç Birsoy studies the regulation of cellular metabolism, particularly in the context of disease. He wants to uncover ways to kill cancer cells, for example, not by dousing them (and non-cancer cells along with them) with poison, but by depriving them of the unique nutrients they need to convert to energy and therefore thrive. To do this, he and his team are re-examining the basics of cellular metabolism using sophisticated genetic tools.
The Challenge
Any activity within and between cells takes energy, whether that cell is a brain cell or a muscle cell or a cancer cell. Different cell types perform different functions and so require a different composition of nutrients. Neurons rely heavily on glucose, muscle cells on amino acids. Cancer cells are no different, though what they need to thrive can differ from other cells (and, indeed, from other cancer cells; cancer is not a single disease).
But how are nutrients transported into the cell and what are their roles in cellular function and metabolic dysfunction? While there is much we have known for decades (the Krebs cycle might stir up memories of freshman biology), the complexity and interconnectedness of the full suite of chemical reactions that compose cellular metabolism means that there is much still to learn, including how environmental and genetic stresses affect metabolism.
Dr. Birsoy’s Approach
The GeneMAP platform can help match transporter proteins with the metabolites they ferry into the cell.
The Birsoy lab is systematically uncovering cancer cell dependencies on nutrients and looking for ways to exploit those vulnerabilities to stall the cell’s metabolic processes.
Dr. Birsoy and his team have also developed—and made freely available online—a discovery platform to map metabolic gene function. More than 5,500 of the approximately 20,000 genes in the human genome are involved in cell metabolism and their dysfunction associated with diseases (and not just cancer). It is one of the first tools designed to match transporter proteins with the nutrients they carry, deepening our understanding of the mechanisms that drive cell metabolism and increasing opportunities for therapeutic innovation.
How This Could Improve Our Lives
Dr. Birsoy and his team are opening new avenues to curb cancer cell proliferation, starving diseased cells while preserving healthy tissue. “Targeted metabolic therapy” includes strategies like disrupting transportation or blocking digestion of nutrients in cancer cells. This could be an effective approach for other diseases as well.
The GeneMAP platform has already identified a transporter associated with choline, an essential nutrient linked with neuroprotective effects. “Many nutrient transporters are associated with neurodegenerative diseases,” Birsoy says. “The more transporters we identify, the more possible treatments we find.”
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