People

Sumeet Khetarpal, MD, PhD

Social media: Twitter @sumeetkhetarpal
Google scholar: https://scholar.google.com/citations?user=J5RasHoAAAAJ&hl=en
Funding: NIH K08 (NHLBI)
https://reporter.nih.gov/search/1_1AemaB-k25uFX22GBYsw/project-details/11031493
Burroughs Wellcome Fund Career Award for Medical Scientists
https://www.bwfund.org/news/bwf-announces-2025-career-awards-for-medical-scientists/

Dr. Sumeet Khetarpal earned his PhD with Dr. Daniel Rader in the Department of Genetics at the University of Pennsyvlania establishing a genetics-to-mechanism framework in lipoprotein biology that now underpins our translational approach. In Zanoni, Khetarpal, Larach et al., Science (2016) (PMID: 26965621), they discovered that a rare loss-of-function variant in SCARB1 paradoxically raises HDL-C yet increases CAD risk, redefining HDL functionality and implicating SR-BI–mediated reverse cholesterol transport in atherosclerosis. In Khetarpal and Schjoldager et al., 2016 (PMID: 27508872), they mechanistically interrogated the GALNT2 lipid GWAS locus, demonstrating how O-linked glycosylation modulates lipoprotein traits—an example of physiology guided by human genetics. In Khetarpal et al., Nature Medicine. 2017 (PMID: 28825717), they characterized a protective missense variant in APOC3, linking altered apoC-III function to lower triglycerides and reduced CAD risk. Together, these studies illustrate how human genetic discovery can reveal unexpected biology in lipid transport and set the stage for therapeutic targeting of atherogenic and metabolically maladaptive lipoproteins.

As a postdoctoral fellow with Dr. Bruce Spiegelman (Dana-Farber) and Dr. Anthony Rosenzweig (MGH), he explored the heart’s endocrine function in exercise and disease. Their work (Khetarpal et al. bioRxiv 2024.01.30.578093; in press at Nature Cardiovascular Research) shows that PGC-1α coordinates mitochondrial adaptation to exercise while suppressing secretion of GDF15, a pro-atrophic signal—establishing a mechanistic link between a core metabolic coactivator and a maladaptive cardio-myokine. In parallel, they developed an extracellular-fluid proteomics platform to catalogue heart-secreted proteins, revealing new candidate mediators of inter-organ communication for targeted follow-up.