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Interview with Kevin Gao

Tuesday, May 26, 2020

Kevin Gao #PutonPurple for Lupus Awareness!

Happy Lupus Awareness month!

Meet our research team member Kevin Gao. Kevin is an MD/PhD student studying lupus and mechanisms of autoimmunity in the labs of Drs. Ann Rothstein and Kate Fitzgerald here at UMass. Kevin is extremely bright, hard-working, and runs interesting and impactful research projects. It was my pleasure to interview him for our blog!

1. Tell me a little about your career/studies.

I'm studying inflammatory diseases for my PhD training and pursuing a dual-degree in Medicine (MD) and Immunology (PhD). I'm aiming for a career as a physician-scientist with my focus on treating and studying autoimmune and autoinflammatory diseases, especially in the fields of rheumatology and dermatology. I'm currently doing my thesis work as a joint student in the labs of Drs. Kate Fitzgerald and Ann Marshak-Rothstein.

2. What first got you interested in studying lupus?

I come from a family of biomedical scientists, and as a kid my parents gifted me a picture book about white blood cells, so I was introduced to the idea of immunology very early on! As a middle schooler, I remember learning about blood transfusion rejection in blood type mismatches, and being interested in how mothers could carry babies with different blood types. It wasn't until years later in medical school that I realized that this indeed could cause disease (primarily seen in rhesus factor mismatch between mother and fetus), and that maternal immunology is incredibly specialized to minimize this risk (especially regarding what antibodies can cross the placental barrier). Thus, as an adolescent I was aware of and drawn to the mystery of how our bodies have a sense of self that changes and adapts to protect us in day to day life, but it wasn't until college that I formally developed an academic interest in immunology and immune diseases.

I first learned about Lupus as more than just a name of a disease (from watching the TV show "House" once), from one of the first friends I made as an undergraduate. My friend lived across the hall from me in my freshman year dorm; she was bright, funny, and always up for an adventure. Then I learned that she was diagnosed with Lupus. I saw how this disease affected her in every day life. She was on drugs to control her disease that made her very susceptible to simple colds, so she was always incredibly careful about getting sick (which is very hard in a dorm). Even so, she still occasionally had flares that not only interrupted her studies but also her opportunities to socialize with her friends. I saw how hard my friend worked to lead a normal life, and admired her for her ability to keep a positive attitude despite the many hardships caused by her disease. And it is because of this friendship that I came to appreciate the struggle that chronic illness brings to people's lives, and became interested in studying how immune diseases could be better treated.

It was also in my undergraduate training that I learned about immune research while working in the molecular pharmacology lab of Dr. Alan Kopin, a physician scientist at Tufts Medical Center. My research during undergrad focused on immune cell chemotaxis via the CCR6-CCL20 axis, which was my entry point to the field of immunology. After graduating, I continued on with immunology research and studies as a research associate in the lab of Dr. Ramnik Xavier where I studied inflammatory bowel diseases and worked with additional physician-scientist mentors that inspired me and further sparked my interests towards translational research in immune mediated diseases. It was through my research experience in Dr. Xavier's lab that I came to learn of the exciting immune research being done at UMass Chan Medical school and its Program of Innate Immunity and Pathology department. I was accepted to UMassMed's MD/PhD program in 2016, and have been there ever since learning and following my interest in the immunology of inflammatory diseases.

3. What is your current research focus?

My PhD thesis work focuses on nucleic acid sensing pathways, which play an important regulatory role in immunity. Interestingly, many of these nucleic acid receptors (like TLR7, TLR9, and cGAS-STING) have been associated with autoimmune and other inflammatory diseases. One big question in the field is: if our body is full of nucleic acids from dangerous pathogens AND from our own tissues, how does our immune system organize itself to tell the difference? Do alterations in this regulation promote inflammatory disease? I'm currently studying a rare genetic disease known as SAVI in which the nucleic acid sensing pathway cGAS-STING is permanently turned as a result of a mutation in the STING protein. Pediatric patients with SAVI develop lung fibrosis and we've developed genetically engineered mice to study how this mutation causes lung disease. We're hoping that this SAVI mouse model will lead to discoveries that can help both SAVI patients, but also more broadly help expand our understanding how rheumatologic disease associated lung diseases arise and how they might be better treated. 

4. What do you think is the future of lupus?

Right now, a lot of the effective drugs for lupus are poorly understood in their function and very broad in their effect. Drugs like systemic corticosteroids are like a massive immune-suppressive "hammer" that treats flares but also put patients in an immunocompromised state that puts them at risk for infectious diseases. Drugs like hydroxychloroquine are thought to interfere with endosomal nucleic acid sensing to mitigate many rheumatologic diseases like lupus, but anti-malarial drugs (like hydroxychloroquine) also have potential toxicities that put patients at risk. I believe that research into immune regulatory networks that contribute to autoimmune diseases will identify new targets for treatment by "biologic agents" (for example targeted monoclonal antibodies) that can more precisely alter immune cell functions to treat disease. Additionally, new drug technologies like PROTAC can help bring more selectivity to small molecule drugs so that specific immune regulatory pathways can be effected on an intracellular level. Moving away from using drugs that function as broad anti-inflammatory hammers towards targeted immune-altering "chisels" has potential to better treat autoimmune diseases with higher efficacy and less side effects.  

5. Any advice for people who want to learn about lupus, or for aspiring scientists?

As a trainee, I feel like I'm still in the middle of figuring out how to align my interests, work, and life together into some kind of balance that can keep me happy and sustained in the future. To be honest, I'm not entirely sure how I was so fortunate to even get this far in having the privilege to do such interesting and important research. What I think I know is that there are many roads to get somewhere, and that "if there's a will, there's a way". So my advice is:
1) Stay on the look out for topics that spark a sense of deep and beautiful mystery in you. There are examples of this every where in nature and medicine. Seeking connection with these fields will inevitably bring richness to your life.
2) Think about how these topics impact everyday life, what problems/short-falls do you see around these topics right now? What can be done to bring changes against these challenges?
3) Follow your nose, don't be shy, and find mentors who are further along the path you are interested in. One way to find your path forward is to understand the trails already blazed by those ahead of you. 

You can follow Kevin on Twitter @ImmunoKevin our our Lupus team account @UMassLupus.

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