Q&A with Ashwin Seetharaman in Toronto

By Quirine Eijkenboom, Featuring Dr. Ashwin Seetharaman

1) NGLY1 is a global team. Where were you born and raised?

I was born and raised in a small city called Madurai in southern India. I came to Canada at the age of 21 to pursue my graduate studies in biology.

2) How did you get into science and how did you end up in the Moffat/Boone lab at the University of Toronto?

India is a land rich in culture. As a child, I grew up in an environment where magical realism and religious stories seamlessly blended into ones outlook when it came to explaining natural phenomena. As a teenager, I felt a deep pull towards philosophy and I was preoccupied with questions pertaining to the origins of the universe and how life was created. This curiosity eventually led me down the path of pursuing a career in science. After graduating with a Ph.D in Molecular Genetics from the University of Toronto, I came across a rare opportunity to interrogate the workings of genetic networks underlying human diseases using the then novel and revolutionary CRISPR-Cas9 technology. I simply could not say no!

3) How did you select your particular area of focus?

Cancer as a disease had fascinated me for as long as I can remember. When it came to choosing a research project, I wanted to work on a topic that would have an impact on our understanding of the genetic networks underlying cancer. Hence, I decided to start my postdoctoral research with a genetic screen for genes that when knocked out using CRISPR, would mediate a heightened sensitivity to a well known-cancer drug, Bortezomib. As fate would have it, the number one hit from that screen was NGLY1.

4) What intrigues you the most when it comes to NGLY1 mechanics?

What intrigues me the most about NGLY1 is how a loss of function in a single gene gives rise to a plethora of clinical symptoms in the affected individuals. Given NGLY1’s role as the key enzyme responsible for deglycosylating substrates within a cell, I believe that its functional reach within the cell is only just coming into prominence. I feel that the current state of knowledge regarding NGLY1’s biological role is but a tip of an incredibly large iceberg. I am very excited for what the coming months and years are going to reveal about the workings of this enzyme.

5) What is one thing people would be surprised to know about your daily work with NGLY1?

A major aspect of my daily work revolves around coordinating an effective teamwork! I believe that one of my major strengths is in being able to effectively collaborate with other scientists from within our lab and outside to interrogate the role of NGLY1 in human cells. I truly believe that great leaps in scientific advancement stems from teamwork and collaboration between scientists.

6) What is the biggest challenge you face in your research today?

One of the biggest challenges we face today is the dwindling federal funding towards supporting basic research

7) What trends in medicine/science are you most excited about?

I am truly fascinated by the idea of personalized medicine. Currently, the available treatment options for the vast majority of diseases are actually quite broad and generic. What I mean here is that the prevailing standard of care administered by healthcare providers is to essentially use an almost identical treatment strategy for different individuals with the same disease or a set of clinical symptoms. While this approach is not necessarily flawed, it can prove highly ineffective at times because it currently does not account for the inherent uniqueness of one's genetic makeup that can make different individuals specifically vulnerable or susceptible to certain diseases/conditions. Hence to address this issue, a growing body of medical practitioners and scientists such as myself are very excited by the prospect of developing a standard of care that is based on the idea of personalized medicine. It is an approach that is rooted in emphasizing the unique ways in which an individual’s disease risks are tied to their genetic makeup and prescribing a treatment regimen that is individualized to their genetic makeup. I believe this is something very well within our reach in the course of the next decade or two.

8) What do you think is going to bring us closer to a cure?

I believe that acquiring a deeper insight into NGLY1’s broader biological role within the cell via experimental approaches such as genetic interaction screens will help us to identify novel therapeutic leads that may lead to a cure in the future.

9) What do you enjoy doing in your free time? How do you unwind after work?

I am a major foodie! When I’m not in the lab I’m mostly exploring the best restaurants in Toronto!

10) Do you have a favorite motto? If yes, what is it?

Yes, and it’s quite simple. Never Give up… Ever.