Dissertation Defense: REDD1 as a Nodal Switch in Cardiac Metabolism
Dissertation Defense: REDD1 as a Nodal Switch in Cardiac Metabolism
Mason Wheeler
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Pfleger Lab, Fralin Biomedical Research Institute at VTC
April 10, 2026, at 2 p.m.
Room G101 A/B, 4 Riverside Circle
About this Dissertation
The heart is extremely energetically demanding, as survival necessitates its constant beating. However, the heart has minimal capacity for energetic and substrate storage, requiring constant generation of ATP to maintain basal contractile function. Notably, many cardiovascular pathologies are characterized by alterations in macromolecule utilization, resulting in an energy starved myocardium and subsequent contractile dysfunction. Thus, identifying key regulators of cardiac substrate utilization in physiology and understanding their dysregulation in pathology is of utmost importance. Herein, Wheeler, mentored by Dr. Jessica Pfleger Karch, describes an investigation into REDD1, an established negative regulator of mTORC1, and a novel mechanism by which REDD1 regulates cardiac substrate utilization. Wheeler found that REDD1 maintains glucose oxidation while suppressing fatty acid oxidation in the heart. Notably, inhibition of mTORC1 did not rescue this altered metabolic phenotype. However, she did find that REDD1 regulates the transcriptional activity of PPAR⍺. Further, bulk RNA-Seq revealed changes in genes involved in fatty acid catabolism, many of which are well established targets of PPAR⍺. This regulation was also found to be independent of mTORC1, but was rescued with PPAR⍺ antagonism. Importantly, Wheeler found that this mechanism drives cardiac hypertrophic remodeling. Taken together, this study demonstrates the first ever mTORC1-independent mechanism for REDD1 in the maintenance of glucose oxidation and suppression of fatty acid oxidation in the heart via PPAR⍺, and describes its relevance in cardiac hypertrophy.
More About the Candidate and Project
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Roanoke College, B.S., Psychology and Biology
Training
Graduate Research Assistant, Pfleger Lab, Fralin Biomedical Research Institute at VTC
Mentor
Jessica Pfleger Karch, Ph.D., Assistant Professor, Baylor College of Medicine
Committee Members
- Shannon Farris, Assistant Professor, Fralin Biomedical Research Institute at VTC
- Samy Lamouille, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC
- Zhen Yan, Ph.D., Professor and Director, Center for Exercise Medicine Research, Fralin Biomedical Research Institute at VTC
Publications
Wheeler M, Renick J, Fawbush R, McAlpin E, Stevens S, Sreedevi K, Warren J, Dennis M, Pfleger Karch J. Cardiac REDD1 alters glucose and fatty acid metabolic gene expression via an mTORC1-independent, PPAR⍺-dependent mechanism and drives hypertrophic growth. In review.
Wheeler M, Pfleger Karch J. The role of REDD1 in cardiac physiology and pathology. In preparation.
Cawley M, Montalvo R, Wheeler M, Pfleger Karch J, Yan Z, Farris S. Elevating neuronal MCU levels in the hippocampus enhances mitochondrial calcium uptake and respiration. In preparation.
Abdelazim H, Alsalman M, Wheeler M, Chappell J. Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation. In submission.
Williams Z*, Payne LB*, Neutel D, Billah M, Thiel W, Wheeler M, Wu X, Renick J, Jourdan J, Pfleger Karch J, Gourdie R. Expression of voltage-gated sodium channel subunit SCN1B splice variants β1 and β1B in rodent cardiac cells. In preparation.
Presentations
Wheeler M, McAlpin E, Stevens S, Fawbush R, Renick J, Williamson D, Dennis M, Pfleger Karch J. REDD1 regulates cardiac metabolism via an mTORC1-independent, PPAR⍺-dependent mechanism and supports hypertrophic remodeling. Invited Speaker for Postdoctoral Position: University of Louisville, Center for Cardiometabolic Science. December 2025.
Wheeler M, McAlpin E, Stevens S, Fawbush R, Renick J, Williamson D, Dennis M, Pfleger Karch J. REDD1 regulates cardiac metabolism via an mTORC1-independent, PPAR⍺-dependent mechanism and supports hypertrophic remodeling. Invited Speaker for Postdoctoral Position: University of Pennsylvania, Perelman School of Medicine. October 2025.
Wheeler M, McAlpin E, Stevens S, Fawbush R, Renick J, Williamson D, Dennis M, Pfleger Karch J. REDD1 regulates cardiac metabolism via an mTORC1-independent, PPAR⍺-dependent mechanism. Oral Presentation: American Heart Association’s Basic Cardiovascular Sciences-Scientific Sessions. July 2025.
Wheeler M, Fawbush R, McAlpin E, Renick J, Stevens S, Williamson D, Dennis M, Pfleger Karch J. Cardiac REDD1 Enhances Glucose and Inhibits Fatty Acid Oxidation Independent of mTORC1 Signaling. Poster Presentation: International Society for Heart Research—North American Section. August 2024.
Wheeler M, Fawbush R, McAlpin E, Renick J, Stevens S, Williamson D, Dennis M, Pfleger Karch J. Cardiac REDD1 Enhances Glucose and Inhibits Fatty Acid Oxidation Independent of mTORC1 Signaling. Oral Presentation: Virginia Tech, Center for Vascular and Heart Research Department Meeting. March 2024.
Wheeler M, Stevens S, Renick J, Dennis M, Pfleger J. REDD1 Is Required for Glucose Metabolism and Insulin Sensitivity in Cardiomyocytes. Poster Presentation: American Heart Association’s Basic Cardiovascular Sciences-Scientific Sessions. July 2023.
Wheeler M, Ibetti J, Koch W, Pfleger J. A Novel Nuclear Role for REDD1 in Cardiac Insulin Resistance and Sensitivity. Poster Presentation: Best of AHA Specialty Conferences: BCVS 2022. American Heart Association’s Scientific Sessions. November 2022.
Wheeler M, Ibetti J, Koch W, Pfleger J. A Novel Nuclear Role for REDD1 in Cardiac Insulin Resistance and Sensitivity. Oral Presentation: The Next Best Thing in Cardiovascular Research. American Heart Association’s Basic Cardiovascular Sciences-Scientific Sessions. July 2022.
- National Heart, Lung, and Blood Institute F31 Ruth L. Kirschstein Predoctoral Individual National Research Service Award
- Inaugural Zeta Beta Tau Graduate Research Fellowship
- 2025 American Heart Association Roanoke Heart Ball – Discovery Honoree
- 2024 FBRI Holiday Party – Inaugural Student Speaker
- 2024 FBRI Retreat Outstanding Graduate Student Talk – 1st Place
- 2022 American Heart Association- Best of AHA Specialty Conferences Invitation
- 2022 CVHR Retreat Poster Award—Honorable Mention
- Invited Lecturer: Pitch Preparation | Translational Biology, Medicine, and Health Commercialization Course | Fall 2024, Fall 2025
- Invited Panelist, Preparing for Your Next Career Step: Graduate School Medical School, and Beyond, Minority Association of Pre-Health Students, Blacksburg, VA | September 2025
- Invited Speaker: Translational Research and Why it Matters | Western Virginia Regional Science Fair | March 2025
- FBRI Annual Retreat Planning Committee | Student Representative | Spring 2024
- Intellectual Property Mentor | Translational Biology, Medicine, and Health Commercialization Course | Fall 2022, Fall 2023
- Invited Panelist, Roanoke Valley Governor’s School STEM Career Panel | March 2023
- President, Vascular and Heart Graduate Student Congress | May 2022-May 2023
- Invited Panelist, Blue Ridge Partnerships for Health Science Careers, Health Science Career Advisory Conference, Roanoke, VA | November 2022
- Social Chair, Roanoke Graduate Student Association | May 2022-May 2023