Richard Bruce Silverman

Silverman attended Central High School of Philadelphia, graduating in the 221st class.[3] Silverman received his B.S. in chemistry from Pennsylvania State University in 1968. He spent one semester at Harvard University before being drafted and serving as a United States Army Physical Sciences Assistant at the Walter Reed Army Institute of Research from January 1969 until his honorable discharge in January 1971. In June 1974 received his Ph.D. from Harvard University in organic chemistry with advisor David Dolphin. He then spent two years as a postdoctoral fellow with Robert Abeles in biochemistry at Brandeis University.[4]

Silverman has been teaching and doing research at Northwestern since 1976. He became both Professor of Chemistry and Professor of Biochemistry, Molecular Biology, and Cell Biology in 1986. He has held several named professorships. He was the Arthur Andersen Professor of Chemistry from 1988 to 1996, the Charles Deering McCormick Professor of Teaching Excellence from 2001 to 2003,[5] and the John Evans Professor of Chemistry beginning from 2004 to 2015.[6] He was named the inaugural Patrick G. Ryan/Aon Professor as of September 1, 2015.[4]

The primary focus in Silverman's laboratory is basic research into central nervous system disorders, including Parkinson’s disease, cerebral palsy, amyotrophic lateral sclerosis, addiction, and epilepsy.[7] Other research areas include cancer (melanoma and hepatocellular carcinoma), lysosomal storage diseases, such as Gaucher's disease, and bacterial infection. He has developed novel approaches to the elucidation of enzyme-catalyzed reactions in organic chemistry.[8] He is particularly interested in understanding and developing mechanisms of enzyme inhibition.[9]

Silverman has published over 360 research articles. He has been awarded at least 85 patents. He has written at least 3 books: Mechanism-based enzyme inactivation: chemistry and enzymology (1988),[10] Organic chemistry of drug design and drug action, now in its third edition (1992, 2004, 2014),[1] and Organic chemistry of enzyme-catalyzed reactions (2000, 2002).[11] He is active on the editorial boards of a number of scholarly journals.[8]

Silverman is well known for inventing the drug pregabalin as a possible treatment for epileptic seizures.[7] During 1988-1990, Ryszard Andruszkiewicz, a visiting research fellow, synthesized a series of molecules for Silverman.[12] One looked particularly promising.[13] The molecule was transported into the brain, where it activated the enzyme L-glutamate decarboxylase. Silverman anticipated that the enzyme would increase production of the inhibitory neurotransmitter GABA and block convulsions.[7] Eventually, the set of molecules were sent to Parke-Davis Pharmaceuticals for testing. In addition to treating seizures, pregabalin was found to be effective in treating fibromyalgia pain, neuropathic pain, and generalized anxiety disorder.[7] It was approved by the FDA in 2004 and marketed by Pfizer (which bought Parke-Davis) under the trade name Lyrica.[7][13]

Research has shown that the mechanism of the drug is more complicated than originally anticipated.[14] In addition to its effects on GABA-AT substrate behavior, pregabalin binds to calcium channels and blocks glutamate release. GABA is potentiated, but through a different mechanism than originally suspected.[15][16]

Lyrica royalties paid to Northwestern, and a gift from Silverman himself, have supported the Silverman Hall for Molecular Therapeutics and Diagnostics at Northwestern University. Silverman Hall, which opened in 2009, was designed to be a collaborative and interdisciplinary facility housing researchers from chemistry, biology, and engineering.[7][30]

• Richard Silverman page on NU Chemistry Faculty website