Joseph Choi
Mitochondrial fatty acid oxidation is facilitated by the combined activities of Carnitine Palmitoyltransferase 1 (Cpt1) and Cpt2, which generate and utilize acylcarnitines, respectively. We compared the response of mice with liver-specific deficiencies in the liver-enriched Cpt1a or the ubiquitously expressed Cpt2 and discovered that they display unique metabolic, physiological and molecular phenotypes. The loss of Cpt1a or Cpt2 results in the induction of the muscle- enriched isoenzyme Cpt1b in hepatocytes in a Ppara-dependent manner. However, hepatic Cpt1b does not contribute substantively to hepatic fatty acid oxidation when Cpt1a is absent. Both the liver-specific double knockout of Cpt1a and Cpt1b, or Cpt2 eliminates the mitochondrial oxidation of nonesterified fatty acids. However, Cpt1a/Cpt1b double-knockout mice retain fatty acid oxidation by utilizing extracellular long-chain acylcarnitines that are dependent on Cpt2. These data demonstrate the noncell-autonomous intercellular metabolism of fatty acids in hepatocytes. Much of the work done targeting mitochondrial ß-oxidation targets Cpt1, but this work shows that there are other metabolites that can feed into the same long-chain fatty acid metabolism. This work was done in Dr. Michael Wolfgang’s lab.
Questions & Answers
Why did you choose Johns Hopkins for your work?
I began working at Johns Hopkins during my undergraduate studies at UMBC, and was fortunate to have met a graduate student who was in the Wolfgang lab at the time. The research that is done at Johns Hopkins is on the cutting edge of science, driving forward incredibly important findings to understand the world we live in.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
I am honored to receive the David Israel Macht Research award. This recognizes the research contribution of the work I’ve done while in the lab of Dr. Michael Wolfgang. One of the graduate students who mentored me when I was here as an undergraduate received the same award. Knowing the outstanding contributions of that student, it is an honor to receive the same
award. Professionally, this award motivates me to continue the pursuit of good research and to not underestimate basic biological pathways in the discovery of new biology.
What contributed to your project’s success?
The incredibly stringent genetic models that this project utilizes was one of the keys to the success of this work. There will never be a perfect model in science — the pathways and interactions are too complex. However, by asking the right questions and utilizing multiple models to understand the results,
we can get closer and closer to a complete understanding. The guidance and insights of lab members and my mentor, Dr. Michael Wolfgang, were the other keys to the success of this project.
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?
Young Investigators’ Day allows for a small window into the incredible amounts and quality of research that is done at Johns Hopkins. Both students and fellows are incredibly hard-working and passionate about the work they do. Young Investigators’ Day allows for a showcase and celebration of all that hard work.
What has been your best/most memorable experience while at Johns Hopkins?
My time in the Wolfgang lab is the best and most memorable experience that I’ve had while at Johns Hopkins. During my time here, I’ve been mentored
by and worked with some of the most incredible scientists and learned an incredible amount.
What are your plans for the next year or so? Graduating, looking for faculty positions, etc.?
I will be graduating in the May 2025 school of medicine convocation, and will be working at the National Cancer Institute as a postdoctoral fellow.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
Outside of the lab, I like to cook!