Matías Fabregat, Ph.D.

Research

In the Galmozzi lab, I will investigate how cancer cells induce the severe weight loss, with muscle and fat wasting, known as cachexia. Cachexia is more than a simple loss of appetite: This cancer-associated disorder rewires an individual’s metabolism, leading to nutritional deficiency, muscle atrophy, adipose lipolysis and, in critical cases, death. Clinical studies show that early in cachexia, adipose cells boost their breakdown of fats. The resulting increase in circulating lipids triggers insulin resistance, inflammation, and metabolic dysfunction. In a set of preliminary experiments, I determined that cells derived from tumor types typically associated with cachexia, such as pancreatic cancer, induce this fat breakdown. I identified several metabolites that are enriched in these cancers. Now, using a suite of advanced techniques in biochemistry, molecular biology, and protein and genome analysis, I will evaluate how these metabolites promote cachexia in cancer models that do not normally develop this wasting condition and assess whether inhibiting their production or secretion reduces the incidence of cachexia. Because little is known about the causes of cachexia, my work could lead to a molecular approach to the early detection and treatment of this devastating cancer-associated complication and potentially revolutionize end-of-life care for those who are at risk.