David H Sherman, PhD
Hans W Vahlteich Professor of Medicinal Chemistry
Professor of Medicinal Chemistry, College of Pharmacy
Professor of Microbiology and Immunology
Professor of Chemistry, College of Literature, Science, and the Arts
Research Professor, Life Sciences Institute
Life Sciences Institute and Department of Medicinal Chemistry
210 Washtenaw Ave
Ann Arbor, Michigan 48109-2216
[email protected]

Available to mentor

David H Sherman, PhD
Professor
  • About
  • Links
  • Qualifications
  • Center Memberships
  • Research Overview
  • Recent Publications
  • About

    Professor Sherman received his undergraduate degree in chemistry at UC Santa Cruz and Ph.D. in synthetic organic chemistry at Columbia University with Gilbert Stork. After four years at Biogen, he moved to the John Innes Institute as a research scientist with Sir Prof. David A. Hopwood. Following 13 years at the University of Minnesota, Prof. Sherman moved to the University of Michigan and is now the Hans W. Vahlteich Professor of Medicinal Chemistry, Professor of Chemistry, and Professor of Microbiology & Immunology. Sherman’s laboratory is in the U-M Life Sciences Institute where his research focuses on the discovery and analysis of bioactive natural products, their metabolic pathways, and diverse biosynthetic enzymes. The functional, structural, and computational analysis of new biocatalysts for late-stage C-H functionalization, polyketide assembly, and pericyclic reactions is a particular focus of the group. Prof. Sherman is faculty lead for the U-M Natural Products Biosciences Initiative and co-founder of the Natural Products Discovery Core.

    Dr. Sherman was founding Director of the Center for Chemical Genomics at the University of Michigan Life Science Institute (2004 – 2013). LSI maintains core facilities covering the areas of high throughput screening and drug discovery, structural biology and protein production with resources to support cross-disciplinary science including genetics; genomics and proteomics; molecular and cellular biology; and structural, chemical and computational biology. Sherman now serves on the advisory board for Michigan Drug Discovery.

    Links
    • Sherman Lab
    Qualifications
    • Postdoctoral Fellow
      Massachusetts Institute of Technology, Center for Cancer Research, 1984
    • PhD
      Columbia University, New York City, 1981
    • BA Chemistry
      University of California, Santa Cruz, Santa Cruz, 1978
    Center Memberships
    • Center Member
      Samuel and Jean Frankel Cardiovascular Center
    • Center Member
      Center for Computational Medicine and Bioinformatics
    • Center Member
      Rogel Cancer Center
    Research Overview

    I have committed over 30 years as an independent investigator to discovering the power and potential of previously unknown chemical compounds made by microorganisms in the natural world and using new technologies to test these compounds against novel targets involved in infectious diseases, cancer, and neurological disorders. My long-term goal in these efforts has been to create and identify promising new therapeutics to improve quality of life through the development of new drugs. My role in the proposed project will focus on developing new macrolide antibiotics in collaboration with Drs. Alan Healy and Emilia Oueis.
    Following my initial training in natural product isolation and total synthesis, my research focus shifted toward understanding the genetic and biochemical basis for assembly and tailoring of complex, microbial derived secondary metabolites. This foundation continues to drive my laboratory to explore and identify new molecules from diverse bacterial and fungal sources, each bringing a unique opportunity to delineate the fascinating biological activities, biosynthetic pathways, enzymes, and multicomponent systems with remarkable catalytic properties. Since beginning my academic career in 1990, my laboratory has driven a series of cross-disciplinary projects, each bringing new perspectives to solve complex problems in the field. Our twenty-year development of a unique microbial natural product extract library (currently >50,000 samples from 10,000 pure culture microbes) is enabling the identification of a multitude of new bioactive metabolites.
    Since 2004, I have worked across schools and units at U-M to build academic drug discovery capabilities, primarily in the Life Sciences Institute, where my lab is located and the library stored and maintained, and in the College of Pharmacy, where I hold tenure and teach. I was the inaugural director of the Center for Chemical Genomics, which provides high-throughput screening, and I am currently faculty Principal Investigator of the U-M Natural Products Biosciences Initiative, which advances compounds and their derivatives toward the clinic.
    U-M represents an exceptionally collaborative and stimulating environment for my research, teaching and outreach/service activities. Since joining the Life Sciences Institute, I have mentored an outstanding and diverse group of chemists, chemical biologists, and microbial biochemists, many of whom have become leaders in their field. During my academic career, I have mentored 67 Ph.D. students, 60 postdoctoral fellows and >85 undergraduates in my laboratory. My engagement in several graduate and NIH training programs has provided an outstanding forum to advise many students in cross-disciplinary research, and career development. Natural product sciences is a global enterprise, and I have advanced research collaborations in numerous countries, teaching short courses, and hosting a diversity of international students, including undergraduates, Ph.D. candidates and visiting professors from Africa, Central and South America, Papua New Guinea, China, Nepal, Peru and the Middle East. These efforts have enabled dynamic and broad perspectives in our field, relating to biodiversity conservation, capacity building, economic development in low/middle income nations, and the key future role for natural products in drug discovery/development relevant to many disease areas.

    Recent Publications See All Publications
    • Journal Article
      Discovering type I cis-AT polyketides through computational mass spectrometry and genome mining with Seq2PKS.
      Yan D, Zhou M, Adduri A, Zhuang Y, Guler M, Liu S, Shin H, Kovach T, Oh G, Liu X, Deng Y, Wang X, Cao L, Sherman DH, Schultz PJ, Kersten RD, Clement JA, Tripathi A, Behsaz B, Mohimani H. Nat Commun, 2024 Jun 25; 15 (1): 5356 DOI:10.1038/s41467-024-49587-1
      PMID: 38918378
    • Journal Article
      Molecular investigation of harmful cyanobacteria reveals hidden risks and niche partitioning in Kenyan Lakes
      Zepernick BN, Hart LN, Chase EE, Natwora KE, Obuya JA, Olokotum M, Houghton KA, Kiledal EA, Sheik CS, Sherman DH, Dick GJ, Wilhelm SW, Sitoki L, Otiso KM, McKay RML, Bullerjahn GS, Consortium N-ILVR. Harmful Algae, 2024 Nov; 102757 DOI:10.1016/j.hal.2024.102757
    • Preprint
      Structure of a Putative Terminal Amidation Domain in Natural Product Biosynthesis
      Rankin MR, Khare D, Gerwick L, Sherman DH, Gerwick WH, Smith JL. bioRxiv, DOI:10.1101/2024.10.28.620694
    • Preprint
      Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System
      Adrover-Castellano ML, Curtis BJ, Schmidt JJ, Glasser CA, Olukorede DE, Qu F, Sherman DH. ChemRxiv, DOI:10.26434/chemrxiv-2024-02cj6-v2
    • Journal Article
      Time-Resolved Ion Mobility-Mass Spectrometry Reveals Structural Transitions in the Disassembly of Modular Polyketide Syntheses.
      Zhao C, Slocum ST, Sherman DH, Ruotolo BT. J Am Soc Mass Spectrom, 2024 Sep 4; 35 (9): 2136 - 2142. DOI:10.1021/jasms.4c00181
      PMID: 39038158
    • Journal Article
      Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation
      McCullough TM, Choudhary V, Akey DL, Skiba MA, Bernard SM, Kittendorf JD, Schmidt JJ, Sherman DH, Smith JL. ACS Catalysis, 2024 Aug 16; 14 (16): 12551 - 12563. DOI:10.1021/acscatal.4c03637
    • Journal Article
      Discovery of Uncommon Tryptophan-Containing Diketopiperazines from Aspergillus homomorphus CBS 101889 Using an Aspergillus nidulans Heterologous Expression System.
      Jenkinson CB, Lin S-Y, Villarreal M, Oakley CE, Sherman DH, Lee C-K, Wang CCC, Oakley BR. J Nat Prod, 2024 Jul 26; 87 (7): 1704 - 1713. DOI:10.1021/acs.jnatprod.4c00113
      PMID: 38990199
    • Journal Article
      Metabologenomics reveals strain-level genetic and chemical diversity of Microcystis secondary metabolism.
      Yancey CE, Hart L, Hefferan S, Mohamed OG, Newmister SA, Tripathi A, Sherman DH, Dick GJ. mSystems, 2024 Jul 23; 9 (7): e0033424 DOI:10.1128/msystems.00334-24
      PMID: 38916306