Dr. Ani Manichaikul is an associate professor in the Center for Public Health Genomics at the University of Virginia. She uses her training in biostatistics to identify regions of the genome and certain DNA variants that would predispose people to disease risk. In particular, Dr. Manichaikul works to improve genetic risk prediction models for people of diverse ancestry.
STEM to the Sky
Feb 1, 2022
When I was a junior in high school, I remember being interested more in the physical sciences rather than biology. At the time, I didn’t think I was that interested in biology, but I grew up pretty close to the NIH. I happened to find a mentor at the National Institute on Deafness and Communication Disorders who was doing studies on deafness and communication disorders, but he himself was a geneticist. It was through him that I got exposure to the field of genetics. He showed me that genetics was a mathematical field. From that experience, I got a chance to analyze some of the datasets, which was really cool for me. It wasn’t exactly at that moment that I decided that’s what I wanted to do, but those were the experiences that made me interested in genetics.
When it was time to decide on what I was going to do after college, I decided to go to graduate school. At the beginning of graduate school, I was thinking of what I wanted to focus on and remembered this great research experience I had. I didn’t really see myself as somebody doing lab experiments, so I decided that I could go into genetics. Genetics requires a lot of data analysis, so I saw it as a good fit for me.
(Credit: Ani Manichaikul)
I got my Ph.D. in biostatistics, and one of my favorite classes that I took in college was an introduction to probability course. I was really fascinated by the stories and anecdotes the professor told about how statistics are incorporated into everyday life. He would explain how statisticians can determine the next best stock picks based on the top 10 outperforming stocks from the past year. They can predict that certain stocks will probably be going down due to the fact that they went up too much last year. He would tell us that you can get in a helicopter on top of the highway between Berkeley and Stanford at rush hour and look at the patterns of the cars moving during a traffic jam. Those patterns of cars may look random, but if you know statistics, you can actually model the way the cars are moving.
I’ve actually been surprised over time to see the way my field has been evolving. Things have gone better for this field than I would have expected in a lot of ways. Over the past 10 years, we’ve been doing a lot of what we call Genome-Wide Association Studies (GWAS). The first of these studies was first published in 2005. At the time people thought it was a long shot that they were going to examine thousands or millions of individual DNA variations across hundreds or thousands of people, and maybe using this type of approach, they would be able to find regions of DNA variation that were associated with disease. At the time, it had never been done before, so people weren’t sure if it would work. It turns out that it worked really well.
We have been doing this over and over again to millions of people for the past 10 or 15 years now. Although we have found DNA variations that are predictive of disease and have confirmed them with repetition, actually translating those discoveries into knowledge that’s useful for doctors or developing drugs has been a lot more challenging.
In terms of my role, I used to imagine that my job was to be an expert at the science part, and that’s it. What was initially surprising was that a lot of my role is about interacting with large numbers of people, managing those relationships, and making sure that we communicate what’s going on in certain projects in order to do the science that we want to do. These projects require a lot of people’s skills and input, so we need to continually communicate with all the different members of our team.
One of the things we would love to do is find a way to use all those DNA variants that we’ve identified and turn them into improvements in health care treatment and prevention. There are already a few examples of that happening. For example, some drugs for kidney disease prevention and lipid-lowering medications have already been approved. Drugs and medications that people didn’t have before the GWAS era are now available through discovery studies and geneticists have been able to translate research into new drugs and therapies. We would love to see more examples of actual treatments that come out of the research that we’re doing.
Besides that, we are now able to apply precision medicine to people’s entire DNA sequence to identify biologically relevant genes that we can use to develop treatments for everybody. The other aspect is developing personalized treatments where you look at an individual’s genome and say, based on your particular DNA sequence, there is a specific type of treatment that would work better for you than it would for other people. We’re not quite there yet, but we do have pretty good progress in terms of an area that we call genetic risk score.
Geneticists in my field are currently working to improve genetic risk predictions to be more accurate for non-European ancestry populations. One of the ways we are doing this is by collecting more DNA samples from diverse ancestry individuals. If we do more genetic studies in diverse ancestries, then we can also build better genetic risk prediction models for multi-ethnic people.
Right now, we are expanding what we’re doing to more diverse ancestry individuals. We have interesting technical or methodological advancements by combining both gene expression and DNA variation together from diverse ancestry people in order to improve personalized health care for more diverse ancestry individuals.
It is also rewarding to do research with people that I am mentoring, such as graduate students, and postdocs. I’ve come to realize it’s really exciting to advance science, but at the same time, science advances slowly. In order to keep science alive and growing, there’s only so much I can do as an individual. To increase my contribution and give back to the field of research, I can accomplish more by mentoring other people so that they can develop their careers and their scientific ideas.
Although I teach, my career is mostly research-focused. For a particular day, we may need to finish writing up the methods section of our paper or finalize figures for a manuscript where we’ve already done a lot of analysis.
For me, the most fun part is actually the data analysis, but there are always some annoyances associated with that. For example, we need to do a lot of data transfer because we may get access to really cool datasets, but they’re not from here. We need to arrange for ways to move them from other universities over to our space so that we can work on the data analysis. Another thing is human subjects protections and internal review boards. Whenever we store human data on our servers, we need to maintain the appropriate permissions to make sure that we’re keeping the participants’ data safe and secure, which is definitely very important.
There are also a lot of meetings with collaborators to coordinate projects that we’re working on. Those can be really exciting because the collaborators usually have some expertise that we don’t, so we can learn from each other and apply complementary skills to conduct interesting research projects.
Work-life balance is a challenge for everybody. If you’re a driven person and you want to do a lot career-wise, you’re always going to feel busy at work and that feeling will never go away. My advice would be to accept that and to not worry about it so much.
I’ve known people who have put off the fun things in life and have delayed what they want to do until they have accomplished what they want to do at work or career-wise. This doesn’t work for me. I feel that if you put off important life events in order to accomplish something in your career, it is an unnecessary delay as you will never really get to that point of accomplishment in your career. Later on, maybe you want to do those fun things in life and you realize that maybe it will take you away from your career as well. There are going to be moments where work will get in the way of family life and vice versa. I try to remind myself that I shouldn’t let my career interfere with my family and life goals.
Research team group hike (Credit: Ani Manichaikul)
It’s really helpful to have a solid technical foundation early on because it’s harder to develop those skills later. For a job like mine, graduate school is so important because you get those few years to concentrate and really develop the foundation of your technical skills. After finishing graduate school, I realized that you don’t get the time to sit back and think deeply about your technical skills and develop them further. You get inundated with lots of other things such as the small tasks you need to do to keep your research going.
Communication and patience skills are also useful. They are definitely important at my current career stage, but there are things that you can develop later on.
Our field is very diverse. Whether you like to do more computer-heavy work, lab work, or work with patients, the field needs all of those different types of scientists. Because the field moves very quickly, It’s also important to pay attention to the trends in science. Try to find the most impactful direction for you: it should be something you find interesting that would also be useful for the field.