Meet a Whitehead Postdoc: Adrianna San Roman

Adrianna San Roman is a postdoc in Whitehead Institute Director and Member David Page’s lab investigating sex differences in human health. San Roman’s work is supported by the Arthur W. Brill and Carol Tobin Brill Postdoctoral Fellowship and an NIH Postdoctoral Fellowship. We sat down with San Roman to learn more about her and her experiences in and out of the lab.

What are you investigating?

In the Page lab, we’re interested in why there are large differences in health and disease between males and females. For example, autoimmune diseases are much more prevalent in women while cardiovascular diseases tend to be more prevalent in men, but we don’t know why these differences occur. I’m trying to understand whether genetic differences between typical females, who have two X chromosomes, and typical males, who have one X and one Y chromosome, result in fundamental biological differences at the level of the cell. In my research, I’m asking the question, does a cell with two X chromosomes look or act differently than a cell with an X and a Y chromosome?

Could you expand on why an XX cell might be different than an XY cell?

A lot of people pay attention to the role of sex hormones in differences between males and females, which is certainly important; however, the role of the sex chromosomes have been overlooked. The Y chromosome has a false reputation of being a genetic wasteland with only one job: to act as a switch that decides whether a developing embryo will form ovaries or testes. However, the Page lab and others have discovered that there are many more important functions for the Y chromosome. One group of Y genes is required for male fertility and another group participates in fundamental cellular processes throughout the body. The latter group is of particular interest because these genes have counterparts on the X chromosome. We think that differences in activity between the X and Y versions of these genes could lead to sex differences.

Similarly, there are misconceptions about the X chromosome that have led to it being overlooked. In order to equalize gene levels between females with two X’s and males with one X, a process called X chromosome inactivation effectively turns off one of the X’s. Superficially, this implies that it doesn't matter if you have two X’s or one; you basically only have one that's active. But a lot of research has shown that about 15 to 30 percent of genes “escape” X chromosome inactivation in females and are active from both X chromosomes. This means that those genes are more active in XX females compared to XY males and may contribute to sex differences.

All together, we think these are good reasons to consider that the genetic differences between XX and XY cells may affect the biochemical makeup of each and every cell in our bodies, which may predispose males and females to different outcomes in terms of health and disease.

What did you want to be when you were a kid?

When I was very little I would tell my mom I wanted to be a cash register. I think I meant a cashier at the grocery store, because I was really into math and counting, and I thought being able to count money all day would be so cool. One of my friends had a toy cash register so we would play with that all day. That was probably the first thing I wanted to be, and after that I wanted to be a scientist.

My parents are both doctors so there was a lot of science exposure growing up for me. I was always really interested in understanding how things worked and why they worked the way they did. My favorite pastime was stealing my parents' white coats, going outside with my friends, and crushing up plants in the backyard or dropping rocks from the top of the play-set and seeing what was inside when they cracked open. I decided around 4th or 5th grade that I wanted to be some sort of scientist, but I don’t think I really understood what that meant until high school when I participated in the Women in Science and Engineering program (WISE) at SUNY Stony Brook. I visited labs and got to meet scientists, which was a fascinating and transformative experience for me in choosing a career path going forward.

What's the coolest thing you've seen in the lab?

For me, the coolest thing is when I finally start to get results after a long time setting up an experiment and get an inkling for what's happening. For example, I've been working with human samples to try to understand how the number of X or Y chromosomes impacts cells. We've been recruiting individuals with different numbers of X and Y chromosomes, which naturally vary in the human population. There are individuals who only have one X chromosome, which is associated with Turner syndrome. These are females, typically of short stature, with a mix of health issues. We also have samples from males with two X chromosomes and a Y; this is associated with Klinefelter syndrome. These are fairly rare populations, so it takes a long time to get enough samples. We've done a lot of work with various clinicians and gotten to know the communities with those syndromes while trying to recruit individuals. When I finally had enough samples to get some initial results it was a very cool and rewarding experience.

What’s it like getting to know the communities with the disorders you study?

I've been very involved with the Turner syndrome community in particular. They have patient advocacy networks and support groups, and they put on huge conferences every year. I've been able to go to a few of those and meet a lot of women with Turner syndrome. It's been very rewarding to talk with them and get to understand their priorities in terms of research questions. You learn things from them that you don’t get from reading medical journals, and you get to know them as people, which I have really enjoyed.

Has getting to know the communities influenced your research?

One thing I learned from talking to women with Turner syndrome is that one of their biggest issues is hearing loss. It’s very common in the Turner syndrome population, and it really affects their day-to-day life. I've been reading up on this and there are some genes on the X and Y chromosomes that may be involved in hearing loss, but this needs much more research to definitively pin down. This was not something that I would have looked into necessarily, until I was made aware of it by talking with them.

What are your hobbies outside of work?

I’m very into cooking and gardening because I consider them both experiments I can eat! My biggest triumph was setting up an automated watering system in my garden to grow plenty of produce for salads all summer long. I also participate in a book club with friends. We read all kinds of books – right now we're reading Michelle Obama's memoir, Becoming. One of my favorites was a fiction book called The Power by Naomi Alderman, about what happens to society when physical dominance shifts from males to females.

What are you passionate about?

Science outreach. Throughout grad school I was involved in an organization called Science in the News, which is run by graduate students at Harvard. We put on a public lecture series every year that was very successful. Since I've been at Whitehead Institute, I've been involved in several programs. One of them is Science Club for Girls, which is a local organization that runs afterschool science programs for girls from elementary through high school. I worked at two different schools, in Cambridge and Somerville, with second and third grade girls. I think it's really cool for the kids to hang out with a scientist in a fun environment and see that scientists can look like them. I think the experiments we do together spark an interest in them at an early age.

I'm also involved with the Whitehead Institute teacher-scientist partners program, which pairs us with teachers to share ideas and act as a resource. I've been working with one teacher, Don Pinkerton from Revere High School, for the last few years. I've gone to Revere to talk about science careers and my research—high school students are very interested in the idea of sex differences so I always have insightful conversations with them. Working with the high school teacher program has made me excited about getting teachers more involved in research. I think it's a cool idea because they take that enthusiasm and knowledge back to the classroom, so it's a way of multiplying your impact.

Where do you see yourself in 10 years?

I would love to have my own lab at a research university. I hope that my career involves teaching and outreach as well as research, and that my lab is welcoming to a diverse group of people at different stages in their careers. I hope that we are studying sex differences in different contexts throughout the body, really trying to understand how the biology connects to differences in health and disease.