The focus of my doctoral training was bioenergetics and cellular metabolism. I had the unique opportunity to receive training both from Case Western Reserve University in partnership with Pennington Biomedical Research Center. I received training from Dr. Charles Hoppel and Dr. John Kirwan, my primary mentor, in analytical approaches to studying cellular respiration in health and disease, with a focus on skeletal muscle and obesity-related tumors. This training revealed the delicacy and durability of metabolic processes such as oxidative phosphorylation in the maintenance of cellular homeostasis. Through this experience, I accumulated expertise and technical proficiency in the study of mitochondrial functions across a spectrum of metabolic diseases including obesity, insulin resistance, and cancer. As a logical extension of this work, I became interested in how metabolic functions of different organs may exacerbate the development of disease, such as obesity.
For my fellowship training, I have gained expertise in clinical and translational research with the goal of developing a research program aimed at improving the lives of those with obesity-related diseases such as cancer. To date, my body of research demonstrates that restricting bioenergetic capacity via pharmacological mitochondrial uncoupling improves metabolic health and dictates the proliferative potential of multiple cancers including hepatocellular carcinoma (HCC). My current research focus is on the regulation of mitochondrial function in metabolic dysfunction-associated steatotic liver disease (MASLD) for liver cancer prevention. The mechanisms whereby MASLD mediates hepatocarcinogenesis remains largely unknown. Bioenergetic remodeling of core energy metabolism is essential to the initiation, survival, and progression of cancer. In the liver, efficiency of the electron transfer system is largely endogenously controlled by uncoupling protein 2 (UCP2), a mitochondrial anion carrier that facilitates the membrane proton translocation. Under normal hepatic conditions, UCP2 is minimally expressed in hepatocytes, primarily residing in Kupffer cells. With the development of MASLD, UCP2 expression in hepatocytes increases to negatively regulate oxidative stress and
mitigate lipotoxicity. Taken together, targeting hepatic bioenergetic efficiency may ameliorate the progression of SLD and prevent HCC. Successful completion of the project, “Hepatic uncoupling protein 2 in metabolic dysfunction-associated hepatocellular carcinoma”, under the mentorship of Drs. John Kirwan and Robert Kesterson, presents tremendous opportunity to develop an independent niche merging mitochondrial physiology and cancer biology disciplines. Furthermore, it creates a platform to support my priority to conduct translational research, merging the unique access to clinical biospecimens available through PBRC and collaborating institutions and my preclinical expertise. My overarching research objective is to investigate mitochondrial plasticity in health and disease to develop and optimize interventions for the treatment and prevention of metabolic diseases such as obesity, insulin resistance, and cancer. The 2024 NORC Pilot and Feasibility Grant will facilitate an independent research project developing critical skills and key data for a transition to independence award application to NCI.
Over the past 6 years of scientific training, I have acquired skills for study design, implementation, analysis, and manuscript preparation, resulting in seven first-author publications and several in high impact journals (Aging Cell, Diabetes, J Cachexia Sarcopenia Muscle, Nature Communications, and EMBO Molecular Medicine).
