Jun Huh attended Seoul National University in Seoul, Korea, where he earned his B.S. and M.S. in microbiology. After serving in the military for over a year, he came to the United States to enroll in a graduate program at California Institute of Technology. He obtained his PhD in Biology after completing his doctoral training, researching apoptosis in Drosophila. Under the mentorship of Dan R. Littman at the NYU School of Medicine, he trained as a postdoctoral fellow studying T-cell immunology with a particular focus on chemical and genetic modulation of pathogenic Th17 cells. In 2015, he was named a Searle Scholar, and in 2016, he was named a Pew Scholar. He currently serves as an Assistant Professor of Microbiology and Immunobiology at Harvard Medical School.
We discussed his recent, groundbreaking research on inflammatory phenotypes in mice and the implications of early stress events in the womb on mouse immunity/central nervous system.
SS: What inspired you to look into this area?
JH: We previously noted that a mouse model displaying autism-like phenotypes produced increased levels of inflammatory cytokines than control when they got challenged with an immune stimulus. This observation and what is known in human patients with autism (some of them also show heightened inflammatory responses) made us wonder what underlies such inflammatory phenotypes. Why does the same mouse display both neurodevelopmental and immunological phenotypes? Perhaps they share some common roots?
SS: Tell us about your research process. How long did it take, where did you conduct this research, and who did you work with?
JH: We mainly use mouse models and take genetic approaches. These generally involve multi-year efforts. For this particular work, I think it might have taken four years.
We usually start from observation. Serendipitous findings or something we read from journals or heard from other people. Then we reiterate and undergo many thought processes involving many "what if" and "how about" questions. We then try to develop one or two key experiments that give us initial confidence to try out our new ideas. Those “key experiments” need to be methodologically simple but give us rather definitive and clean answers. We spend a fair amount of time designing such experiments in many cases.
SS: Even though your study findings have not yet been confirmed in humans, what insight do you think they can offer into central nervous and immune system problems in individuals with autism spectrum disorders?
JH: Our study indicates that an event that occurred very early on (such as exposure to inflammation in the maternal womb) can have long-lasting effects later on, even on two seemingly unrelated tissues such as the CNS and the immune system of adult offspring. I didn’t have evidence, but those autistic patients with immune-related symptoms may be due to their early exposure to uncontrolled immune responses during pregnancy? Of course, it is pure speculation, at least for now.
SS: What are you most proud of in terms of your research thus far?
JH: So far, most if not all papers coming out of my lab have co-first authors and (even better) co-senior authors. We often teamed up with other labs with distinct approaches and expertise. We can do some exciting science tackling questions from multiple angles in doing so. So I think I am good at collaborating with other people, of which I am very proud.
SS: What is the broader, long-term significance of your findings?
JH: Many fascinating biological processes take place during pregnancy. However, we know so little about it. It is an incredibly understudied area. We essentially lack molecular, cellular, and immunological understandings about how pregnancy affects women’s immune systems and fetal brain development (let alone offspring’s immune system). Our findings provide another example showing how important it is to understand better what underlies and happens during pregnancy.
SS: What areas of exploration are you interested in now as a result of your new research findings?
JH: We found that offspring’s immune cells, more specifically T cells, remembered what happened during pregnancy, through the help of bacteria in maternal guts, by changing how their DNA is wrapped around in the nucleus. I would like to understand how mom’s bacteria influence offspring’s immune cells.
SS: Is there anything else you would like to add?
JH: Thank you for your interest in our work. Most, if not all, difficult work was done by highly talented postdoctoral fellows, Eunha Kim and Donggi Paik. So they are the ones who should get credits.
About the Author
Sophia Scott is a freshman at Harvard College concentrating in Human Evolutionary Biology.
We discussed his recent, groundbreaking research on inflammatory phenotypes in mice and the implications of early stress events in the womb on mouse immunity/central nervous system.
SS: What inspired you to look into this area?
JH: We previously noted that a mouse model displaying autism-like phenotypes produced increased levels of inflammatory cytokines than control when they got challenged with an immune stimulus. This observation and what is known in human patients with autism (some of them also show heightened inflammatory responses) made us wonder what underlies such inflammatory phenotypes. Why does the same mouse display both neurodevelopmental and immunological phenotypes? Perhaps they share some common roots?
SS: Tell us about your research process. How long did it take, where did you conduct this research, and who did you work with?
JH: We mainly use mouse models and take genetic approaches. These generally involve multi-year efforts. For this particular work, I think it might have taken four years.
We usually start from observation. Serendipitous findings or something we read from journals or heard from other people. Then we reiterate and undergo many thought processes involving many "what if" and "how about" questions. We then try to develop one or two key experiments that give us initial confidence to try out our new ideas. Those “key experiments” need to be methodologically simple but give us rather definitive and clean answers. We spend a fair amount of time designing such experiments in many cases.
SS: Even though your study findings have not yet been confirmed in humans, what insight do you think they can offer into central nervous and immune system problems in individuals with autism spectrum disorders?
JH: Our study indicates that an event that occurred very early on (such as exposure to inflammation in the maternal womb) can have long-lasting effects later on, even on two seemingly unrelated tissues such as the CNS and the immune system of adult offspring. I didn’t have evidence, but those autistic patients with immune-related symptoms may be due to their early exposure to uncontrolled immune responses during pregnancy? Of course, it is pure speculation, at least for now.
SS: What are you most proud of in terms of your research thus far?
JH: So far, most if not all papers coming out of my lab have co-first authors and (even better) co-senior authors. We often teamed up with other labs with distinct approaches and expertise. We can do some exciting science tackling questions from multiple angles in doing so. So I think I am good at collaborating with other people, of which I am very proud.
SS: What is the broader, long-term significance of your findings?
JH: Many fascinating biological processes take place during pregnancy. However, we know so little about it. It is an incredibly understudied area. We essentially lack molecular, cellular, and immunological understandings about how pregnancy affects women’s immune systems and fetal brain development (let alone offspring’s immune system). Our findings provide another example showing how important it is to understand better what underlies and happens during pregnancy.
SS: What areas of exploration are you interested in now as a result of your new research findings?
JH: We found that offspring’s immune cells, more specifically T cells, remembered what happened during pregnancy, through the help of bacteria in maternal guts, by changing how their DNA is wrapped around in the nucleus. I would like to understand how mom’s bacteria influence offspring’s immune cells.
SS: Is there anything else you would like to add?
JH: Thank you for your interest in our work. Most, if not all, difficult work was done by highly talented postdoctoral fellows, Eunha Kim and Donggi Paik. So they are the ones who should get credits.
About the Author
Sophia Scott is a freshman at Harvard College concentrating in Human Evolutionary Biology.
