Harel Weinstein, D.Sc.Tri-Institutional Professor
Weill Cornell Medical College
Chair, Department of Physiology and Biophysics
Director, Institute for Computational Biomedicine
The Weinstein lab studies complex systems in physiology with methods of molecular and computational biophysics, bioinformatics and mathematical modeling. It focuses on the structural and dynamic mechanisms of cellular components, including macromolecular assemblies of proteins and the membrane. Computational modeling and simulation provide insight into the involvement of these cellular components in fundamental biological processes such as signal transduction, neuronal signaling and regulation of cell growth. The lab then examines how these mechanisms, studied at the molecular scale, and the macromolecular processes they underlie, coalesce into physiological functions of organized systems in tissues and organs. The work combines theoretical and computational methods of biophysics with experimental designs in large-scale collaborations. New methods for such simulations based on quantum and statistical mechanics, mathematical modeling and informatics are being designed and implemented in these studies.
Current research themes include the mechanisms of molecular recognition and allostery of micromachines involved in signal transduction, such as G protein coupled receptors, neurotransmitter transporters and multidomain scaffolding and adaptor proteins. The lab studies how macromolecular dynamics, oligomerization and encounter-complex formation execute cellular signaling and how it is possible to modulate, remodel and repair these mechanisms through molecular and genomic interventions. The biomedical end points for these particular studies are neurotransmission in health and disease, drug abuse mechanisms and cancer.
- Zhao, Y. et al. Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue. Nature 474, 109–113 (2011).
- Shan, J. et al. The substrate-driven transition to an inward-facing conformation in the functional mechanism of the dopamine transporter. PLoS ONE 6, e16350 (2011).
- Zhao, Y. et al. Single-molecule dynamics of gating in a neurotransmitter transporter homologue. Nature 465, 188–193 (2010).