Associate Professor, Medicinal Chemistry
Telephone: (206) 616-4586
Website: Nath Lab
- B.A. (Chemistry and Biology), University of Virginia
- Ph.D. (Medicinal Chemistry/Biomolecular Structure & Design), University of Washington
- Postdoc (Molecular Biophysics & Biochemistry), Yale University
- Protein aggregation in Alzheimer’s disease and related dementias
- Protein self-assembly
- Biologics and protein-based therapeutics
Taking Students: Yes
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 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.
The Nath lab is interested in understanding the roles of protein dynamics in human health and disease. Proteins display a fascinating spectrum of dynamic behavior, ranging from some that are almost static to others that rapidly interconvert between a diverse ensemble of structures. The nature, amplitude and timescales of protein conformational fluctuations can be crucial to biological functions such as enzyme catalysis and intracellular signaling. Mutations, post-translational modifications and environmental factors can perturb protein dynamics – and hence normal function – in ways that are difficult to predict.
Abhi and his group are developing new and powerful methods to characterize and control protein dynamics, building on recent advances in biophysics, biochemistry and pharmacology from groups around the world. They focus on proteins involved in degenerative disorders (such as Alzheimer’s disease), the oxidative stress response, and drug metabolism.
Low molecular weight ligands bind to CYP3A4 via a branched induced fit mechanism: Implications for O2 binding. Arch Biochem Biophys. 2023 May 1;739:109582. doi: 10.1016/j.abb.2023.109582. Epub 2023 Mar 21.
MitoNEET’s Reactivity of Lys55 toward Pyridoxal Phosphate Demonstrates its Activity as a Transaminase Enzyme. ACS Chem Biol. 2022 Oct 21;17(10):2716-2722. doi: 10.1021/acschembio.2c00572. Epub 2022 Oct 4.
Structure-Activity Relationships of Novel Tau Ligands: Passive Fibril Binders and Active Aggregation Inhibitors. ACS Chem Biol. 2022 Mar 18;17(3):701-708. doi: 10.1021/acschembio.2c00012. Epub 2022 Feb 11.
Probing interactions of therapeutic antibodies with serum via second virial coefficient measurements. Biophys J. 2021 Sep 21;120(18):4067-4078. doi: 10.1016/j.bpj.2021.08.007. Epub 2021 Aug 10.
Corrigendum to “In vitro to in vivo extrapolation of the complex drug-drug interaction of bupropion and its metabolites with CYP2D6; simultaneous reversible inhibition and CYP2D6 downregulation” [Biochem. Pharmacol. 123(2017)85-96]. Sager JE, Tripathy S, Price LSL, Nath A, Chang J, Stephenson-Famy A, Isoherranen N. Biochem Pharmacol. 2021 Jan;183:114306. doi: 10.1016/j.bcp.2020.114306. Epub 2020 Nov 5.
Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage. Shen T, Penewit K, Waalkes A, Xu L, Salipante SJ, Nath A, Werth BJ. J Antimicrob Chemother. 2021 Jan 19;76(2):292-296. doi: 10.1093/jac/dkaa422.
Rapid Formation of Peptide/Lipid Coaggregates by the Amyloidogenic Seminal Peptide PAP248-286. Vane EW, He S, Maibaum L, Nath A. Biophys J. 2020 Sep 1;119(5):924-938. doi: 10.1016/j.bpj.2020.07.029. Epub 2020 Aug 6.
Release of a disordered domain enhances HspB1 chaperone activity toward tau. Baughman HER, Pham TT, Adams CS, Nath A, Klevit RE. Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):2923-2929. doi: 10.1073/pnas.1915099117. Epub 2020 Jan 23.
Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of ‘quasi-ordered’ states. Clouser AF, Baughman HE, Basanta B, Guttman M, Nath A, Klevit RE. Elife. 2019 Oct 1;8:e50259. doi: 10.7554/eLife.50259.