Abhinav Nath

Assistant Professor

Department of Medicinal Chemistry, Medicinal Chemistry Faculty, Nath Lab, Plein Center in Geriatrics Faculty

Expertise: Computational Modeling, Fluorescence, Molecular Biophysics, Neurodegeneration, Protein Dynamics

Telephone: (206) 616-4586

Email: anath@uw.edu

Website: Lab website

Education

  • PhD in Medicinal Chemistry, 2008, University of Washington
  • Bachelor of Arts in Biology and Chemistry, 2003, University of Virginia
  • Postdoctoral studies, Yale University

Research Interests

Understanding the roles of protein dynamics in neurodegenerative disease, drug metabolism, and the body’s response to oxidative stress.

Biography

Abhinav “Abhi” Nath earned his BA (in Biology and Chemistry) from the University of Virginia in 2003, and his PhD (in Medicinal Chemistry and Biomolecular Structure & Design) from the University of Washington in 2008, where he worked with Nelson Endowed Professor of Medicinal Chemistry Bill Atkins on understanding the mechanisms of substrate binding by cytochrome P450s and other drug-metabolizing enzymes. He then moved to Yale University for postdoctoral training with professors Liz Rhoades and Andrew Miranker, where he was an American Heart Association Postdoctoral Fellow and studied intrinsically disordered and amyloid-forming proteins using single-molecule fluorescence and computational methods.

Research Overview

Protein molecules display a variety of conformational fluctuations, over a broad range of timescales, that are often fundamental to their normal function and roles in disease. Protein dynamics underlie such diverse molecular processes as enzyme catalysis, drug transport, motor protein function, and signal transduction. Moreover, a significant fraction of human proteins are so dynamic that they do not fold into a single well-defined state. This behavior is challenging to characterize and control by conventional structural biology and drug design approaches.

The Nath lab focuses on understanding the relationship between protein dynamics and normal function or pathological dysfunction, and on developing new tools to study and ultimately modulate functionally relevant conformational fluctuations. We use a broad range of experimental and theoretical approaches from biochemistry, biophysics and pharmacology, including, in particular, single-molecule fluorescence spectroscopy and computational simulations. Systems of interest include the Glutathione-S-Transferase enzyme superfamily (involved in drug metabolism and the response to oxidative stress) and the intrinsically disordered protein Tau (implicated in Alzheimer’s disease and pathology due to traumatic brain injury).

Selected Publications

  • Nath A, Schlamadinger DE, Rhoades E, Miranker AD. “Structure-based small molecule modulation of a pre-amyloid state: pharmacological enhancement of IAPP membrane-binding and toxicity.” Biochemistry 2015 May 12 [Epub ahead of print]. PubMed link.
  • Kumar S, Brown MA, Nath A, Miranker AD. “Folded small molecule manipulation of islet amyloid polypeptide.” Chem Biol. 2014 June 19; 21(6):775-81. PubMed link.
  • Munro JB, Nath A, Farber M, Datta SA, Rein A, Rhoades E, Mothes W. “A conformational transition observed in single HIV-1 Gag molecules during in vitro assembly of virus-like particles.” J Virol. 2014 Mar; 88(6):3577-85. PubMed link.
  • Nath A, Rhoades E. “A flash in the pan: dissecting dynamic amyloid intermediates using fluorescence.” FEBS Lett. 2013 Apr 17; 587(8):1096-105. PubMed link.
  • Nath A*, Sammalkorpi M, DeWitt DC, Trexler AJ, Elbaum-Garfinkle S, O’Hern CS,* Rhoades E*.  “The Conformational Ensembles of α-Synuclein and Tau: Combining Single-Molecule FRET and Simulations.” Biophys. J. 2012 Nov 7; 103(9):1940-9. PubMed link.
  • Smith WW, Schreck CF, Hashem N, Soltani S, Nath A, Rhoades E, O’Hern CS.  “Molecular Simulations of the Fluctuating Conformational Dynamics of Intrinsically Disordered Proteins.” Phys. Rev. E. 2012 Oct; 86:041910. PubMed link.
  • Nath A, Miranker AD, Rhoades E.  “A Membrane-bound Antiparallel Dimer of Rat Islet Amyloid Polypeptide.” Angew. Chem. Int. Ed. 2011 Nov 11; 50(46):10859-62. PubMed link.