Sky Dominguez always knew she wanted to go to medical school: With a strong interest in neuroscience, she conducted Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) research throughout her undergraduate career at The Ohio State University, and after completing a summer research training program at the University of California, San Francisco, Dominguez decided that research would be an integral part of her medical school experience.
Now a student in Feinberg’s Medical Scientist Training Program (MSTP), Dominguez studies the correlations between sex, chronic stress and Alzheimer’s disease. Her most recent study, published in the Journal of Alzheimer’s Disease, explores the biological mechanisms underlying a sex difference in Alzheimer’s disease: approximately two-thirds of those with the disease are women.
Motivated by the historical lack of female study participants and animal subjects in laboratory tests, Dominguez sought to uncover if chronic stress would induce a similar response in male Alzheimer’s disease mouse models compared to females. What she found is that several biological pathways were changed differently between males and females in response to chronic stress, suggesting why women may be at a higher risk of developing Alzheimer’s disease than men.
Read a Q&A with Dominguez below.
Why did you choose Feinberg?
When I was applying to MD/PhD programs, Northwestern was actually one of the last schools I applied to. I didn’t know if Northwestern was going to be a good fit for me, to be honest, but when I came to visit Feinberg my mind changed immediately. I knew coming in that the MSTP was great, but the people here especially made me feel like Feinberg would be a good match and that it was a good community to be part of. The culture of collaboration here was really clear to me and something I was really looking forward to being involved with. It was nice to see that here the research does come first and people come first.
Why did you choose to pursue this research topic?
I was always very interested in the brain and how psychology and biology interact, so when I was applying for colleges, I was very adamant about going somewhere with a neuroscience program. Personally, I had a grandfather who suffered from a stroke and seeing how that completely changed not only his physical abilities, but also his personality, was very difficult for me. This was something I was very much interested in learning more about, along with generally learning more about neurodegenerative disorders or brain trauma.
As an undergraduate student, I conducted Alzheimer’s disease and ALS research and my final honors thesis project was investigating how stress impacted the development of both diseases. One of the big things I learned in doing my honors thesis is that previous studies mainly used only male animal models, most likely because investigators didn’t want to deal with the estrous cycle or female hormones generally. Because of that, most of the research that we have today is only using male mouse models. That’s a big issue when you’re developing medicine and treatments because when you administer it to female patients, you have no idea if it’s going to have a different effect than in male patients.
So, when I was looking for labs to rotate with here at Northwestern, I saw that Hongxin Dong had an RO1 grant specifically for sex, stress and Alzheimer’s disease research. I thought it was perfect because I wanted to transition into research that was very translational. When I came to Feinberg, she was already working in that field and she also has an MD/PhD, so she really understood where I was coming from with trying to make sure that this research is applicable to human patients and not simply bench science.
Were your findings surprising?
We were surprised that memory deficits weren’t shown. We thought stress would induce some change in that regard. What was also interesting was in which sexes the tau pathway was affected in, because recent literature said that stress affecting Alzheimer’s was specifically tau-mediated. Seeing that pathway come up in both males and females was really interesting to see. More importantly, females showed robust change in these pathways, which was something I thought was very interesting and motivating.
Do you plan to pursue the study further?
One of the things that’s of interest to me is if different stressors have different effects in Alzheimer’s disease patients, especially in a gender-specific way. For example, right now I’m comparing isolation stress, which is a social stressor, to physical stressors such as restraint.
What are your future plans?
I knew coming into an MD/PhD program that I wanted to either pursue neurology or psychiatry. Now that I’m a little further into my graduate school career, I’m definitely leaning more toward psychiatry. Ideally, I would like to have my own lab and be able to see patients and I really want to be able to do something where my lab is informed by the patients.
