Andrew Love
I’ve spent the past two years working in Dr. Michael Kornberg’s lab studying the role of NAD metabolism in the pathogenesis of multiple sclerosis (MS). MS is an autoimmune disorder that targets oligodendrocytes, which are the cells that myelinate our neurons, similar to how rubber insulates copper wires allowing for electric conduction. Oligodendrocytes are matured from oligodendrocyte progenitor cells (OPC), which in a healthy person would initiate remyelination programs in the face of demyelinating attacks like in MS. In patients with MS, however, OPCs take on a destructive inflammatory phenotype that helps propagate inflammatory attacks on matured myelinating oligodendrocytes.
What’s interesting is that these inflammatory OPCs upregulate the levels of an enzyme called NAMPT, which is responsible for synthesizing NAD in our cells. I have been trying to understand why these cells upregulate that enzyme, and what happens when its inhibited. I’ve found that NAMPT inhibition in the inflammatory OPCs is able to reduce a lot of the pathologic and damaging activities of these cells by specifically: decreasing the expression of genes that code for antigen processing and presentation machinery, limiting the expression of MHC-I on the inflammatory OPCs, and reducing the activation of CD8 T cells. Our understanding of how bioenergetics and metabolism regulate inflammatory activities is a continually growing field, and my project has helped shine a light on how one metabolic enzyme, NAMPT, is involved. A lot of current MS drugs reduce new inflammatory attacks on the central nervous system, but there are none that address ways to reinitiate myelination in the aftermath of these attacks. My research suggests that NAMPT within inflammatory OPCs may be a crucial target to both reduce inflammation and keep OPCs on track to mature into myelinating glia.
Questions & Answers
Why did you choose Johns Hopkins for your work?
As an aspiring physician-scientist who wanted to pursue M.D./Ph.D. training, I knew during my gap years I wanted to be in a place that would provide me with two important things: strong mentorship and rigorous research training. Compared to other research post-bacs, Hopkins PREP seemed to be a place that would give me the guidance and support to be a competitive applicant, with MCAT and application writing tutoring support, research experience that mirrored the expectations of early Ph.D. students with mini-thesis meetings and chalk talk practice, financial support to attend research conferences, opportunities for clinical shadowing and involvement in a patient population that matters deeply to me, and endless near-peer support from current M.D./Ph.D. students who had recently gone through this application process.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
As an underrepresented-in-medicine (URM) trainee, it has long been difficult to really see myself as a scientist and feel like I am meant to be in these types of spaces and institutions. Personally, this award affirms the idea that I am a scientist and have the capability to succeed in rigorous research training. Professionally, I think this helps build credibility for my research contributions and helps demonstrate my productivity during my time at Hopkins.
What contributed to your project’s success? (Special skills, interests, opportunities, guidance, etc.)
There are a lot of things that contributed to my success, but I would say above all else the mentorship from my PI, Dr. Michael Kornberg, and my in-lab mentor, cellular and molecular medicine Ph.D. candidate Judy Lee, have been the biggest, most meaningful parts of my success. I only had 10 weeks of summer research experience before I came to Hopkins, and so I had such a high bar to clear in terms of learning how to do a lot of things in the lab and getting comfortable with the ups and downs of biomedical research. Their mentorship in not only teaching me practical skills like how to do RNA isolation for a qPCR experiment and when to do T-testing versus one-way ANOVA, but more so how science works and how to navigate research when experiments fail, how to think about controls and reproducibility, how to present research effectively, all those non-technical skills I think have been really important. I genuinely believe their mentorship and the way they’ve each poured into me has been the bedrock of my own success both here at Hopkins but especially in my next chapter of training.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
I absolutely love the idea of Young Investigators’ Day! I think so often it feels like your productivity in science and worth as a scientist gets reduced to your number of publications and your h-index score. For young trainees like myself who may not have those standard representations of our productivity, YID offers a forum to celebrate what we have done and also build connections with other YID awardees. Since I am a post-bac, the other awardees are people just a few years ahead of me doing the things I hope to be doing one day, and I think it is amazing to have formal support from an institution to celebrate these things.
What has been your best/most memorable experience while at Johns Hopkins?
So many things, it’s hard to choose! One that stands out to me though is a few months after being at Hopkins, I got involved with an initiative led by Dr. Alexis Coslick in the PM&R department volunteering at their evening clinics doing physicals for student athletes from Baltimore City schools. I was taking vitals one night, and as I took a teen’s blood pressure, I said out loud it was reading as normal, but his mom noted that in the past his blood pressure had been abnormally high. But she quickly renounced her statement, saying, “But I’m not a doctor, you probably know more.” And when she said that, I laughed and said I also wasn’t a doctor, and that I was glad that she said that, and I would add that note on his form, thanking her for speaking up. It was a funny moment, but it made me realize how important it is to encourage folks to speak up and for me to be constantly conscious of what it might mean when someone is perceiving you as the “high and mighty doctor in the white coat.” Most of my time at Hopkins has been spent in the lab at the bench, but volunteering with the physical night clinic kept me close to clinical medicine and also affirmed my interest in community engagement revolving around primary care, particularly with boys and young men, something I want to keep being involved with as a trainee.
What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?
With my last few months in PREP and in the Kornberg Lab, I am trying to wrap up a few more experiments for a publication before I move to Chicago this summer to start as an M.D./Ph.D. student in the Medical Scientist Training Program at the University of Chicago Pritzker School of Medicine!
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
Interest-wise, I absolutely love watching Bravo series (reality TV for those unfamiliar) because not only is it funny, but I think reality TV is often a really insightful contextual analysis of a lot of the dynamics of race, gender, class and sexuality in society and politics in the United States. I briefly flirted with the idea of being a sociology major in college, so I can’t help but think about those things when watching lol! Life experience-wise, my junior year of college I went on an immersion trip to the Galapagos Islands, and while it made me certain I could never be a field biologist, it was a really cool opportunity to see wild animals and witness all the things I would eventually learn about in my evolution class, in real life!