Research

Research Header

Research Statement

Our research program investigates how the heart communicates with other organs to regulate systemic metabolism, and how these pathways can be targeted to treat cardiovascular and metabolic disease. We focus on two intertwined axes of inter-organ crosstalk: (i) lipoprotein physiology and lipid signaling that shape cardiometabolic risk, and (ii) heart-derived secreted proteins (“cardio-myokines”) that govern adaptation to exercise and drive maladaptive remodeling in disease. Methodologically, the lab integrates mouse genetics and physiology (exercise and heart-failure models), viral vector–mediated gene delivery, primary cell culture, quantitative proteomics and lipidomics, and human genetic/proteomic datasets.

The Khetarpal lab will extend this genetics-to-mechanism paradigm across three synergistic thrusts: (1) discover and define heart-derived proteins that control systemic metabolism and cardiac remodeling (leveraging ECF proteomics, gain/loss-of-function, and receptor/ligand mapping); (2) dissect how lipoprotein regulators (e.g., APOC3-centered pathways) influence cardiac and skeletal-muscle bioenergetics and endothelial function in exercise vs. heart failure; and (3) translate these insights using human genetic and proteomic resources to prioritize therapeutic entry points. This integrated program offers trainees rigorous, multi-modal training at the interface of basic metabolism, cardiovascular biology, and human genetics, with a clear path from discovery to translational relevance.

Key questions the Khetarpal lab seeks to answer

  1. How do cardiac cells communicate with each other and with other oxidative tissues through secreted factors to adapt to exercise?
  2. How do dyslipidemia and maladaptive diets—and their reversal with exercise—reshape inter-organ communication between the heart, muscle, and adipose tissue?
  3. Which myokines act as “good” vs. “bad” signals in heart failure, and how do they molecularly alter disease progression?
  4. How do PGC-1α–driven adipose and muscle mitochondrial function influence cardiac health and susceptibility to heart failure?