Dr. Evripidis Gavathiotis is an Associate Professor in the Department of Biochemistry and the Department of Medicine at Albert Einstein College of Medicine. He is a faculty member of the Einstein’s Center of Experimental Therapeutics, the Albert Einstein Cancer Center, the Wilf Family Cardiovascular Research Institute, the Institute of Aging Research and the Gottesman Institute for Stem Cell Biology and Regenerative Medicine. Dr. Gavathiotis grew up in Athens, Greece and received his bachelor degree in Chemistry from the University of Crete in 1998. He received his Ph.D in Biological Chemistry from the University of Nottingham in 2002 studying the structural mechanism of DNA-binding anti-cancer drugs. He worked at De Novo Pharmaceuticals in the Drug Design and Discovery department applying in silico drug design and lead optimization approaches for several therapeutic targets. Dr. Gavathiotis pursued post-doctoral fellowships at the Rockefeller University studying the structural and molecular biology of apoptosis signaling and at the Dana-Farber Cancer Institute and Harvard Medical School, where he studied the BCL-2 family of proteins in apoptosis and cancer. In 2009, Dr. Gavathiotis was appointed Instructor in the Department of Pediatrics at Harvard Medical School and then joined the faculty of Einstein in 2011. His research includes chemical biology, structural biology, medicinal chemistry and translational approaches to investigate novel mechanisms of protein interactions in cell death and cell survival signaling that cause cancer and other diseases with the aim to develop novel therapeutics. Dr. Gavathiotis has co-authored 45 scientific publications and 15 United States patent applications. Dr. Gavathiotis has received numerous honors and awards throughout his career including the NIH Pathway to Independence Award, the AHA Scientist Development Award and Scholar Awards from the Gabrielle’s Angel Foundation for Cancer Research, the Sidney Kimmel Foundation for Cancer Research and the Alexandrine and Alexander L. Sinsheimer Foundation. He received the 2014 Young Chemical Biologist Award by the International Chemical Biology Society and the 2015 Pershing Square Sohn Prize for Young Investigators in Cancer Research. More recently, he received the Collaborative Science Award from AHA, an Award from the Melanoma Research Alliance, the Irma T. Hirschl Career Scientist Award and for his entrepreneurial activities he received the NYC BioAccelerator Award.
1. Dr. Gavathiotis, congratulation on your recent paper in Cancer Cell [9:32(4):490-505]. Could you give us a brief summary of your findings, their importance on the cancer field and what you do plan to look at next?
Our paper demonstrates a novel therapeutic approach for Acute Myeloid Leukemia (AML). It describes the discovery of a first-in-class small molecule that directly activates pro-apoptotic protein BAX to induce apoptosis in human AML cells in vitro and in vivo. BAX is a critical pro-apoptotic protein that upon its activation it induces mitochondrial dysfunction and release of pro-apoptotic factors from the mitochondria to enable the caspase cascade of the apoptotic program. Several chemotherapy and targeted cancer therapeutics indirectly promote apoptosis to kill cancer cells and this requires activation of BAX to execute its deadly activity. Our paper established BAX activation as a druggable target for AML and provides a detailed mechanism of action of our preclinical lead BTSA1 for future development of BAX activators as cancer therapeutics.
The mainstay of drug targeting for apoptosis in cancer for the past 15 years has focused on anti-apoptotic BCL-2 proteins, which are overexpressed in the majority of cancer cells to ensure inhibition of BAX and other pro-apoptotic members. Our work demonstrates that direct activation of pro-apoptotic proteins such as BAX is an alternative strategy to promote apoptosis in cancer cells and it is also well tolerated in normal cells. Our work unravels a new powerful approach against the resistance of cancer cells to undergo cell death and opens new opportunities for combinatorial treatment with other cancer therapeutics in resistant and aggressive tumors.
Our work next focuses on three different areas. First, we are evaluating and comparing additional compounds as BAX activators with the goal to select a candidate for Investigational New Drug application and clinical trials. Second, we want to evaluate our preclinical lead in additional tumors and patients samples to identify the tumors that our compound has significant efficacy as single agent but also as combination with other chemotherapeutics. These studies will further inform us about the broad potential and limits of our therapeutic strategy and this information would guide future clinical trials. Third, we are using our new tools to investigate BAX activation and induction of apoptosis in other cellular contexts and diseases that have dysfunctional apoptotic program.
2. What do you find the most exciting and the most challenging thing about your research?
In my lab, we currently work in some basic and fundamental questions but we also like to ask broader questions and think ways how we can use our findings to better serve people and provide solutions to patients. This process of taking fundamental information, for example, of how molecules and atoms interact, and try to apply it to real life problems to me is the most exciting part of our research. However, this process becomes more challenging as more variables come into play and we are dealing with more complex systems. Despite the challenges, I find that there are many opportunities to get excited by doing discovery research. I believe this is one of the most rewarding aspects of our job.
3. How difficult was the transition from a postdoc to an Assistant Professor and then an Associate Professor?
Every career transition in the academic career ladder has its own challenges. Securing an Assistant Professor position from a postdoc position has different requirements from securing an Associate Professor position. In our times obtaining a faculty position from a postdoc has become a very competitive process requiring several scientific accomplishments. Moreover, our academic system cannot offer as many faculty positions and only a small fraction of postdocs are promoted to a faculty position. Likewise, when you successfully pass this stage and have a faculty position, you are required to perform several activities such as recruiting and managing the lab personnel, teaching, participating in administrative committees, disseminate your research and build a research program that is long-term funded, despite the fact that federal funding has become extremely competitive. Nevertheless, having recently going through these challenges, I strongly believe that preparation, hard work, and perseverance ultimately deliver success.
4. What is your advice to PhD candidates and postdocs who are pursuing a career in the Biomedical Sciences?
I have a few suggestions for the young scientists who are pursuing a career in the Biomedical Sciences. It is imperative to find an important research topic that will fascinate them and keep them enthused to work. They should try to become experts on a technique but they should also learn as many skills they can. Maintaining a broad understanding of their science and reading papers on their research topic but also on research outside their research area is important for generating new ideas and form new hypotheses. They should realize their career goals depending on their interests and strengths and talk to their mentors, advisors and network and learn how to prepare themselves and achieve their goals. Finally, they should always remember that there are often disappointments in research. Therefore, they will need to learn to have patience and persistence.
5. As a member of HBA-USA, how do you view its efforts to promote interactions between scientists in Greece and the USA and how would you like to see the HBA evolving in the next years?
First of all, I would like to take the opportunity to congratulate all of you that have been taking an active role and offer your time and service to HBA-USA. The initiative to promote interactions and exchange of experiences between scientists in Greece and USA is a great effort and should be further promoted and supported. These interactions will enhance our network, expand our reach and facilitate new opportunities for collaboration. I believe such efforts will increase the research productivity in Greece and eventually will stimulate the growth of the economy and improvement of the standard of living. In the next years, I would like to see HBA-USA to expand its initiatives and organize international conferences and workshops to generate opportunities for educational, research and entrepreneurial collaborations between scientists of Hellenic heritage from the USA and the rest of the world.