Albert Einstein College of Medicine
We study protein interaction mechanisms in the cell death pathway that are deregulated in cancer. We aim to elucidate these mechanisms and then develop innovative approaches to correct these mechanisms.
Our goal is to translate our insights into therapeutic strategies and small molecules drugs that can serve the basis for novel cancer therapies.
We apply novel concepts and chemical tools to develop novel pharmacological strategies that promote cell death in cancer cells.
Evripidis Gavathiotis, Ph.D, is an Associate Professor in the Departments of Biochemistry and Medicine of the Albert Einstein College of Medicine and a member of the Experimental Therapeutics Program at the Albert Einstein Cancer Center. Dr. Gavathiotis received a B.Sc. in chemistry from the University of Crete in 1998 and a Ph.D in the area of biological and biophysical chemistry of DNA-damaging anti-cancer drugs from the University of Nottingham in 2002. He then worked in the pharmaceutical industry applying in silico drug design and lead optimization approaches for several therapeutic targets. Dr. Gavathiotis pursued postdoctoral training at the Rockefeller University in structural biology of programmed cell death proteins and at Dana-Farber Cancer Institute and Harvard Medical School, where he focused on cancer chemical biology of the BCl-2 family of proteins and apoptosis. In 2011, Dr. Gavathiotis joined the faculty of Einstein where he uses chemical and structural biology to investigate protein interactions that modulate cell death and survival signaling pathways and contribute to cancer and other diseases. He also applies an interdisciplinary approach to translate such new insights into small molecule drugs to treat cancer. He has made important scientific contributions to the understanding of mechanisms underlying cell death and identification of novel pharmacological strategies. He has earned numerous awards including the NIH Pathway to Independence Award and Scholar Awards from the Sidney Kimmel Foundation, the Gabrielle’s Angel Foundation and the Alexandrine and Alexander Sinsheimer Fund. He received the 2014 Young Chemical Biologist Award by the International Chemical Biology Society.
Expanding A Pharmacological Approach To Selective Apoptosis Induction For Cancer Therapy
Apoptosis is a physiological death process that regulates the critical balance between cellular life and death to maintain homeostasis. When apoptosis is deregulated, it can contribute to tumor pathogenesis, maintenance and resistance to chemotherapy. Pro-apoptotic BAX is protein that operates as gateway to apoptosis and upon its activation, it open holes to the mitochondria, the essential organelles for energy production in the cell, leading to cellular demise.
“The Prize gives me the freedom and support to take bold steps in establishing new concepts in cancer biology and developing novel drugs for cancer patients. The Pershing Square Sohn Prize is the catalyst to transform my laboratory’s science into real-life solutions.”
The goal of this proposal is to investigate activation of BAX using small molecule drugs as a therapeutic approach for cancer. We have developed the first small molecules that directly activate BAX and showed that this strategy can promote potent apoptosis in select cancer cell lines. Here, we propose to progress our lead molecules into preclinical development and identify combinations of other drugs that can sensitize our lead BAX activators to potently induce apoptosis in cancer cells. Moreover, we want to identify proteins that keep apoptosis and BAX suppressed in cancer cells and when they are eliminated or blocked in combination with our BAX activator, cancer cells will be sensitized to apoptosis and die. We plan to investigate various aggressive tumor cell lines such as pancreatic, non-small cell lung cancer, colorectal and leukemia and validate our conclusions in mouse xenograft models of human tumor cells. Our work will aim to develop new knowledge on apoptosis regulation of cancer cells and innovative pharmacological strategies that may lead to effective therapies for cancer patients.
“Innovation is an important component for solving challenging problems and breaking new ground in science. My laboratory will apply innovative approaches with the ultimate goal to develop novel treatments for cancer patients.”