Zach Zappala is a CEHG graduate fellow in the lab of Stephen Montgomery. He is a graduate of The College of New Jersey (BS, Biology and Computer Science). His research focuses on statistical methods for identifying the genetic basis of rare complex traits.
Can you tell us a bit about yourself, personally and professionally?
I’m a 5th year PhD student in Genetics. I grew up (and went to college) in New Jersey before moving to California. When I was an undergraduate, I majored in biology and computer science; I have been interested in using computational methods to solve biological problems ever since I was 17 and first started working in a research lab. During college, I spent a summer living in Tokyo while taking Japanese language classes.
I came to Stanford straight after I completed my undergraduate degree, and have really enjoyed living in northern California. I like to travel and enjoy hiking around the Bay Area. I especially like skiing in Tahoe during the winter, and try to get outdoors as much as possible.
How did you end up here? What got you interested in genetics and science?
When I was in high school, I really liked working with computers, writing code, and coming up with novel solutions for problems I encountered. I was obligated to do a scientific internship when I was 17, and I enjoyed applying all of my computational skills to the genetics problems I was working on. As an undergrad, I decided that I would like to continue on and get a PhD and I continued doing research (although most of my work was at the bench!).
Can you tell us about your current research and what you want to achieve with it?
My current research has been focused on developing methods that can identify the genetic basis of extreme traits (either disease status or some other human trait). I have been trying to do this for mutations that impact gene regulation, which is generally pretty difficult for rare mutations. I’ve spent a lot of time studying a cohort of families from Sardinia, Italy, where my closest collaborators are from.
The island of Sardinia is particularly interesting for genetic studies because, while it was first inhabited thousands of years ago, it has remained relatively genetically isolated. As a result, the distribution of mutations on the island is unique relative to geographically close regions due to drift and selection. Additionally, Sardinians have elevated risks for autoimmune disorders like type 1 diabetes and multiple sclerosis, and they have historically experienced significant exposure to malaria until its rather recent eradication. By looking at families, we are better able to capture the effect of rare mutations that are transmitted from parents to children, and can use these events to understand the genetic mechanisms underlying gene regulation and disease risk in these individuals.
Additionally, we are now working to bring these methods into the clinic in order to understand Mendelian diseases that result from non-coding variation. Such scenarios are difficult to approach with exome and whole genome sequencing. As a result, only about 30% of rare disorders are “diagnosed” – meaning that the causal mutation (or affected gene) has been successfully identified. By studying gene expression in rare disease patients, we are hoping to increase the diagnostic success rate for clinical genome centers and improve the care and treatment of these patients.
Were there people in particular to whom you would attribute your professional success?
There are so many people that have been a huge part of any successes I’ve achieved – all of my mentors and advisors, collaborators, and lab mates have played an integral role. In our current lab, several of us often work very closely together on a few projects, helping out where our own particular expertise applies.
Can you speak a bit to the role you see CEHG playing on Stanford campus?
I think that CEHG plays a unique role for the scientific community here at Stanford – for one, it brings together labs in different departments that, while separated on paper (and on campus), work and think about the same kinds of things all the time. Having a formal Center through which these labs can interact loops these people together, and is better for everyone.
What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you?
Looking back, I think I would have benefited from taking some time off between my undergraduate degree and graduate school – while this isn’t necessarily true for everyone, I had trouble adjusting to the different kinds of academic pressures that exist in graduate school. However, I have no regrets – doing a PhD has been an incredibly fun and rewarding experience, and I have met some of the most incredibly interesting people I know here at Stanford and at conferences I’ve traveled to.