Genentech: Matthew Volgraf | Principal Scientist (Chemistry), Discovery Chemistry

Scientists / Our Scientists

"I’m motivated by the opportunity to work with talented colleagues on the toughest scientific problems."

13

Years at Genentech

18

Publications at Genentech

4

Awards & Honors

I joined Genentech in 2010 after completing my PhD at UC Berkeley with Prof. Dirk Trauner, followed by a postdoctoral fellowship at Memorial Sloan Kettering Cancer Center with Prof. David Gin. My academic background in chemical biology and natural product total synthesis prepared me for the collaborative, multi-disciplinary team environment which is central to Genentech’s culture.

Featured Publication

Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design.

J Med Chem. 2016 Mar 24;59(6):2760-79.

Volgraf M, Sellers BD, Jiang Y, Wu G, Ly CQ, Villemure E, Pastor RM, Yuen PW1, Lu A, Luo X, Liu M, Zhang S, Sun L, Fu Y, Lupardus PJ, Wallweber HJ, Liederer BM, Deshmukh G, Plise E, Tay S, Reynen P, Herrington J, Gustafson A, Liu Y, Dirksen A, Dietz MG, Liu Y, Wang TM, Hanson JE, Hackos D, Scearce-Levie K, Schwarz JB.

My current role in the Discovery Chemistry department has been focused on developing small molecule drugs targeting ion channels within the neuroscience and immunology therapeutic areas. I am interested in studying the principles of drug design targeting membrane-bound enzymes and receptors, together with the physicochemical rules governing blood-brain barrier penetration.

Cryo-EM reveals an unprecedented binding site for NaV1.7 inhibitors enabling rational design of potent hybrid inhibitors

eLife, ISSN: 2050084X

Marc Kschonsak; Christine C. Jao; Christopher P. Arthur; Alexis Rohou; Philippe Bergeron; Daniel F. Ortwine; Steven J. McKerrall; David Hackos; Lunbin Deng; Jun Chen; Tianbo Li; Peter Dragovich; Matthew Volgraf; Matthew Wright; Jian Payandeh; Claudio Ciferri; John C. Tellis

Ligand binding at the protein–lipid interface: strategic considerations for drug design

Nature Reviews Drug Discovery, ISSN: 14741784 14741776

Jian Payandeh; Matthew Volgraf

A Retrospective Look at the Impact of Binding Site Environment on the Optimization of TRPA1 Antagonists

ACS Medicinal Chemistry Letters, ISSN: 19485875

Elisia Villemure; Jack A. Terrett; Larouche-Gauthier; Martin Déry; Huifen Chen; Rebecca M. Reese; Shannon D. Shields; Jun Chen; Steven Magnuson; Matthew Volgraf

Tetrahydrofuran-Based Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonists: Ligand-Based Discovery, Activity in a Rodent Asthma Model, and Mechanism-of-Action via Cryogenic Electron Microscopy

Journal of Medicinal Chemistry, ISSN: 15204804 00222623

Jack A. Terrett; Huifen Chen; Daniel G. Shore; Elisia Villemure; Larouche-Gauthier; Martin Déry; Francis Beaumier; Léa Constantineau-Forget; Chantal Grand-Maître; Luce Lépissier; Stéphane Ciblat; Claudio Sturino; Yong Chen; Baihua Hu; Aijun Lu; Yunli Wang; Andrew P. Cridland; Stuart I. Ward; David Hackos; Rebecca M. Reese; Shannon D. Shields; Jun Chen; Alessia Balestrini; Lorena Riol-Blanco; Wyne P. Lee; John Liu; Eric Suto; Xiumin Wu; Juan Zhang; Justin Ly; Hank La; Kevin Johnson; Matthew Baumgardner; Kang-Jye Chou; Alexis Rohou; Lionel Rouge; Brian S. Safina; Steven Magnuson; Matthew Volgraf

A Non-covalent Ligand Reveals Biased Agonism of the TRPA1 Ion Channel

Neuron, ISSN: 10974199 08966273

Chang Liu; Rebecca M. Reese; Simon Vu; Lionel Rouge; Shannon D. Shields; Satoko Kakiuchi-Kiyota; Huifen Chen; Kevin Johnson; Yu Patrick Shi; Tania Chernov-Rogan; Demi Maria Zabala Greiner; Pawan Bir Kohli; David Hackos; Bobby Brillantes; Christine Tam; Tianbo Li; Jianyong Wang; Brian S. Safina; Steven Magnuson; Matthew Volgraf; Jian Payandeh; Jie Zheng; Alexis Rohou; Jun Chen

A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment

Journal of Experimental Medicine, ISSN: 15409538 00221007

Alessia Balestrini; Victory Joseph; Michelle Dourado; Rebecca M. Reese; Shannon D. Shields; Lionel Rouge; Daniel D. Bravo; Tania Chernov-Rogan; Cary D. Austin; Huifen Chen; Lan Wang; Elisia Villemure; Daniel G. Shore; Vishal A. Verma; Baihua Hu; Yong Chen; Laurie Leong; Chris Bjornson; Kathy Hötzel; Alvin Gogineni; Wyne P. Lee; Eric Suto; Xiumin Wu; John Liu; Juan Zhang; Vineela D. Gandham; Jianyong Wang; Jian Payandeh; Claudio Ciferri; Alberto Estevez; Christopher P. Arthur; Jens Kortmann; Ryan L. Wong; Jose Heredia; Jonas Martin Doerr; Min Jung; Jason A. Vander Heiden; Merone Roose-Girma; Lucinda Tam; Kai H. Barck; Richard A. D. Carano; Han Ting Ding; Bobby Brillantes; Christine Tam; Xiaoying Yang; Simon S. Gao; Justin Ly; Liling Liu; Liuxi Chen; Bianca M. Liederer; Joseph Lin; Steven Magnuson; Jun Chen; David Hackos; Justin Elstrott; Alexis Rohou; Brian S. Safina; Matthew Volgraf; Rebecca N. Bauer; Lorena Riol-Blanco

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models

Cell Reports, ISSN: 22111247

Jesse E. Hanson; Keran Ma; Justin Elstrott; Martin Weber; Sandrine Saillet; Abdullah S. Khan; Jeffrey Simms; Benjamin Liu; Thomas A. Kim; Gui-Qiu Yu; Yelin Chen; Tzu-Ming Wang; Zhiyu Jiang; Bianca M. Liederer; Gauri Deshmukh; Hilda Solanoy; Connie Chan; Benjamin D. Sellers; Matthew Volgraf; Jacob B. Schwarz; David Hackos; Robby M. Weimer; Morgan Sheng; T. Michael Gill; Kimberly Scearce-Levie; Jorge J. Palop

TRPA1 modulation by piperidine carboxamides suggests an evolutionarily conserved binding site and gating mechanism

Proceedings of the National Academy of Sciences of the United States of America, ISSN: 10916490 00278424

Tania Chernov-Rogan; Eleonora Gianti; Chang Liu; Elisia Villemure; Andrew P. Cridland; Xiaoyu Hu; Elisa Ballini; Wienke Lange; Heike Deisemann; Tianbo Li; Stuart I. Ward; David Hackos; Steven Magnuson; Brian S. Safina; Michael L. Klein; Matthew Volgraf; Vincenzo Carnevale; Jun Chen

Discovery of a Potent (4 R,5 S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling

Journal of Medicinal Chemistry, ISSN: 15204804 00222623

Huifen Chen; Matthew Volgraf; Steven Do; Aleksandr Kolesnikov; Daniel G. Shore; Vishal A. Verma; Elisia Villemure; Lan Wang; Yong Chen; Baihua Hu; Aijun Lu; Guosheng Wu; Xiaofeng Xu; Po-Wai Yuen; Yamin Zhang; Shawn D. Erickson; Martin Dahl; Christine Brotherton-Pleiss; Suzanne Tay; Justin Ly; Lesley J. Murray; Jun Chen; Desiree Amm; Wienke Lange; David Hackos; Rebecca M. Reese; Shannon D. Shields; Joseph P. Lyssikatos; Brian S. Safina; Anthony A. Estrada

A novel NMDA receptor positive allosteric modulator that acts via the transmembrane domain

Neuropharmacology, ISSN: 18737064 00283908

Tzu-Ming Wang; Brandon M. Brown; Lunbin Deng; Benjamin D. Sellers; Patrick J. Lupardus; Heidi J. A. Wallweber; Amy Gustafson; Evera Wong; Matthew Volgraf; Jacob B. Schwarz; David Hackos; Jesse E. Hanson

Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability

Journal of Medicinal Chemistry, ISSN: 15204804 00222623

Xiaojing Wang; Aleksandr Kolesnikov; Suzanne Tay; Grace Chan; Qi Chao; Steven Do; Jason H. Drummond; Allen Ebens; Ning Liu; Justin Ly; Eric Harstad; Huiyong Hu; John Moffat; Veerendra Munugalavadla; Jeremy Murray; Dionysos S. Slaga; Vickie Tsui; Matthew Volgraf; Heidi J. A. Wallweber; Jae H. Chang

GluN2A-selective pyridopyrimidinone series of nmdar positive allosteric modulators with an improved in vivo profile

ACS Medicinal Chemistry Letters, ISSN: 19485875

Elisia Villemure; Matthew Volgraf; Yu Jiang; Guosheng Wu; Cuong Q. Ly; Po-Wai Yuen; Aijun Lu; Xifeng Luo; Mingcui Liu; Shun Zhang; Patrick J. Lupardus; Heidi J. A. Wallweber; Bianca M. Liederer; Gauri Deshmukh; Emile G. Plise; Suzanne Tay; Tzu-Ming Wang; Jesse E. Hanson; David Hackos; Kimberly Scearce-Levie; Jacob B. Schwarz; Benjamin D. Sellers

Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design

Journal of Medicinal Chemistry, ISSN: 15204804 00222623

Matthew Volgraf; Benjamin D. Sellers; Yu Jiang; Guosheng Wu; Cuong Q. Ly; Elisia Villemure; Richard Pastor; Po-Wai Yuen; Aijun Lu; Xifeng Luo; Mingcui Liu; Shun Zhang; Liang Sun; Yuhong Fu; Patrick J. Lupardus; Heidi J. A. Wallweber; Bianca M. Liederer; Gauri Deshmukh; Emile G. Plise; Suzanne Tay; Paul Reynen; James Herrington; Amy Gustafson; Yichin Liu; Akim Dirksen; Matthias G. A. Dietz; Yanzhou Liu; Tzu-Ming Wang; Jesse E. Hanson; David Hackos; Kimberly Scearce-Levie; Jacob B. Schwarz

Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function

Neuron, ISSN: 10974199 08966273

David Hackos; Patrick J. Lupardus; Teddy Grand; Yelin Chen; Tzu-Ming Wang; Paul Reynen; Amy Gustafson; Heidi J. A. Wallweber; Matthew Volgraf; Benjamin D. Sellers; Jacob B. Schwarz; Pierre Paoletti; Morgan Sheng; Qiang Zhou; Jesse E. Hanson

Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors

Bioorganic and Medicinal Chemistry Letters, ISSN: 14643405 0960894X

Matthew Volgraf; Lina Chan; Malcolm P. Huestis; Hans E. Purkey; Michael Burkard; Mary K. Geck Do; Julie Harris; Kevin W. Hunt; Xingrong Liu; Joseph P. Lyssikatos; Sumeet Rana; Allen A. Thomas; Guy Vigers; Michael Siu

Discovery of 7-tetrahydropyran-2-yl chromans: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid β-protein (Aβ) in the central nervous system

Journal of Medicinal Chemistry, ISSN: 15204804 00222623

Allen A. Thomas; Kevin W. Hunt; Matthew Volgraf; Ryan J. Watts; Xingrong Liu; Guy Vigers; Darin Smith; Douglas Sammond; Tony P. Tang; Susan P. Rhodes; Andrew T. Metcalf; Karin D. Brown; Jennifer N. Otten; Michael Burkard; April Cox; Mary K. Geck Do; Darrin Dutcher; Sumeet Rana; Robert K. Delisle; Kelly Regal; Albion D. Wright; Robert Groneberg; Kimberly Scearce-Levie; Michael Siu; Hans E. Purkey; Joseph P. Lyssikatos; Indrani W. Gunawardana

Diethylaminosulfur trifluoride-mediated intramolecular cyclization of 2-hydroxycycloalkylureas to fused bicyclic aminooxazoline compounds and evaluation of their biochemical activity against β-secretase-1 (BACE-1)

Tetrahedron Letters, ISSN: 00404039 18733581

Malcolm P. Huestis; Wendy Liu; Matthew Volgraf; Hans E. Purkey; Christine Yu; Weiru Wang; Darin Smith; Guy Vigers; Darrin Dutcher; Kevin W. Hunt; Michael Siu

Switchable Proteins and Channels

Molecular Switches, Second Edition,

Matthew Volgraf; Matthew Banghart; Dirk Trauner

University of California, Berkeley, Ph.D in Chemistry – 2008
University of Pennsylvania, B.A. in Chemistry – 2003

ACS Medicinal Chemistry Division Young Investigator Symposium, Speaker – 2016
American Cancer Society Postdoctoral Fellow – 2008-2010
Roche Excellence in Chemistry Award – 2007
ACS Medicinal Chemistry Division Predoctoral Fellowship – 2006