George Khelashvili

About

George Khelashvili, Ph.D., is an Associate Professor of Physiology and Biophysics and an Associate Professor of Computational Biophysics in the Institute for Computational Biomedicine at Weill Cornell Medicine. His research focuses on uncovering dynamic mechanisms in fundamental biological processes of signal transduction by cell surface proteins, including receptors such as G protein-coupled receptors (GPCRs), transporters in the family of Neurotransmitter:Sodium-Symporters (NSS), and lipid scramblases. His work emphasizes understanding how the spatial organization and function of these molecular machines are regulated by the cell membrane, its components like cholesterol and various lipids, and interactions with other proteins within the cell environment. Dr. Khelashvili approaches these topics using advanced quantitative methods of theoretical and computational biophysics, integrating biophysical theory and computation with biophysical measurements and molecular cell biology experimentation. His interdisciplinary and multi-scale strategies interpret experimental insights into membrane-associated signaling proteins within a novel quantitative framework, providing mechanistic insights into how membrane properties and remodeling influence protein function, organization, and signaling, which are of major importance to cell physiology.

Research topics

• Chemistry
• Biochemistry
• Biology
• Biophysics
• Cell biology
• Materials science

Selected publications

• How cholesterol stiffens unsaturated lipid membranes

  Proceedings of the National Academy of Sciences · 2020 · 392 citations

  H NMR) spectroscopy, and molecular dynamics (MD) simulations-we report that cholesterol locally increases the bending rigidity of DOPC membranes, similar to saturated membranes, by increasing the bilayer's packing density. All three techniques, inherently sensitive to mesoscale bending fluctuations, show up to a threefold increase in effective bending rigidity with increasing cholesterol content approaching a mole fraction of 50%. Our observations are in good agreement with the known effects of…

  DOI

• Localization atomic force microscopy

  Nature · 2021-06-16 · 196 citations

  articleOpen access
  PublisherOA PDFDOI

• CD19 CAR antigen engagement mechanisms and affinity tuning

  Science Immunology · 2023-03-03 · 69 citations

  articleOpen access

  Chimeric antigen receptor (CAR) T cell therapy relies on T cells that are guided by synthetic receptors to target and lyse cancer cells. CARs bind to cell surface antigens through an scFv (binder), the affinity of which is central to determining CAR T cell function and therapeutic success. CAR T cells targeting CD19 were the first to achieve marked clinical responses in patients with relapsed/refractory B cell malignancies and to be approved by the U.S. Food and Drug Administration (FDA). We rep…

  PublisherOA PDFDOI

• Phospholipid Scrambling by G Protein–Coupled Receptors

  Annual Review of Biophysics · 2021 · 41 citations

  1st authorCorresponding

  Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein-coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin and its apoprotein opsin, are constitutively active as scramblases in vitro. In liposomes, opsin sc…

  PublisherOA PDFDOI

• <i>BTG1</i> mutation yields supercompetitive B cells primed for malignant transformation

  Science · 2023-01-19 · 40 citations

  articleOpen access

  Multicellular life requires altruistic cooperation between cells. The adaptive immune system is a notable exception, wherein germinal center B cells compete vigorously for limiting positive selection signals. Studying primary human lymphomas and developing new mouse models, we found that mutations affecting BTG1 disrupt a critical immune gatekeeper mechanism that strictly limits B cell fitness during antibody affinity maturation. This mechanism converted germinal center B cells into supercompeti…

  PublisherOA PDFDOI

Recent grants

• Rhodopsin dimerization: mechanistic basis and functional consequences

  NIH · $2.2M · 2017–2022

• NIH Grant R21EY028314

  NIH · $466k · 2020

Frequent coauthors

• Harel Weinstein

  Cornell University

  141 shared

• Jonathan A. Javitch

  New York State Psychiatric Institute

  71 shared

• Michael V. Levine

  Cornell University

  43 shared

• Michel Bouvier

  Université de Montréal

  42 shared

• Jufang Shan

  42 shared

• Jean‐Philippe Pin

  Université de Montpellier

  42 shared

• Marta Filizola

  Icahn School of Medicine at Mount Sinai

  41 shared

• Milka Doktorova

  University of Virginia

  39 shared

Similar researchers at Cornell University

• Olivier Elementoh-150
• Karsten Suhreh-119