Alexander Soukas, MD, PhD
Dr. Soukas received his Sc.B. in Biomedical Engineering from Brown University, M.D. (Alpha Omega Alpha) from Cornell University Medical College, and Ph.D. in molecular genetics from the Rockefeller University. He completed medical residency at the Brigham and Women’s Hospital and endocrinology, diabetes and metabolism fellowship at MGH. He is recipient of numerous awards including the Ellison Medical Foundation New Scholar in Aging Award, the Charles H. Hood Award in Child Health, and the Howard M. Goodman Fellowship.
Questions being addressed in the lab
Projects underway to answer these questions
To determine how fat mass and starvation survival is regulated, we use the genetic model system elegans, a barely visible roundworm. We use genome-wide functional genomic approaches to screen for fat regulatory pathways and starvation resistance. To date we have identified almost 500 genes that regulate fat metabolism and starvation resistance, 80% of which are conserved all the way to humans. As predicted, there is an incredible enrichment for 1) genes that cause both high fat and enhance starvation survival when knocked down or knocked out, and there is 2) genes that cause low fat mass and starvation sensitivity. Our major goal is now to decipher how this complex group of genes network to adapt to different nutrient levels to enable the most efficient metabolism and starvation defenses. Our hypothesis is that by understanding this gene network we will be able to identify how these genes contribute to regulation of metabolism in humans and contribute to obesity and diabetes.
In order to study the response to the antidiabetic drug metformin we use the power of gene discovery in C. elegans to illuminate genetic pathways necessary for the drug to act. We then bring discoveries to mammalian models of metformin action. We are collaborating with human geneticists to interface genetic pathways with understanding of the human genetic determinants of metformin action. We recently discovered an ancient pathway conserved from worm to human by which metformin extends lifespan and blocks cancer growth (Wu et al., Cell 2016, In Press.)
We have been studying early events in insulin signaling in the liver to figure out several key questions: 1) how does insulin resistance start in the liver? 2) why does fatty liver develop in diabetes? And 3) are there therapeutic targets for diabetes in the liver that can help increase insulin sensitivity without promoting fatty liver disease? To study insulin signaling events, we model insulin signaling both in mammalian liver cells in culture and in mouse knockouts missing key signaling molecules in insulin signaling.
Highlighted Publications from the lab
An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer