Andrew M. Gulick PhD

Andrew Gulick

Andrew M. Gulick
PhD

Professor

Department of Structural Biology

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Bacterial Pathogenesis; Infectious Disease; Metalloenzymes; Microbial Pathogenesis; Microbiology; Protein Function and Structure; Structural Biology

Contact Information
Jacobs School of Medicine and Biomedical Sciences
955 Main St
Buffalo, New York 14203-1121
Phone: (716)829-3696
amgulick@buffalo.edu



Professional Summary:

My research program aims to understand how bacteria produce natural products, small molecules that are secreted from the cell to adapt to diverse environments. These molecules allow the bacteria to compete with other microbes or, in the host-pathogen setting, to establish or exacerbate an infection. Natural product biosynthesis may therefore serve as a target for antimicrobial development.

My lab uses a variety of techniques to examine these pathways. A core approach is to use X-ray crystallography to determine the molecular structure of proteins that catalyze important steps in natural product biosynthesis. Structural observations are tested and validated using biochemical techniques to examine the catalytic reactions. Finally, molecular and cellular techniques are used to examine biosynthetic gene cluster activity in the cell. These studies will inform efforts to engineer enzymes to produce novel natural product and identify new products of previously uncharacterized pathways.

I have a long-standing interest in the Nonribosomal Peptide Synthetases (NRPSs), a family of large, multidomain enzymes that produce important peptide natural products like the antibiotic vancomycin or the anticancer agent bleomycin. NRPSs operate like an assembly line in which the nascent peptide is attached to a carrier domain that shuttles the synthetic intermediates to neighboring catalytic domains. The carrier and catalytic domains are often joined in a single polypeptide that is thousands of residues in length. By examine the crystal structures of large NRPS proteins, we have determined some of the features that enable this fascinating biosynthetic mechanism.

Many NRPS products are siderophores, small molecules that bind iron and are required for growth in the pathogenic environment. My lab also studies aerobactin, an NRPS-independent siderophore pathway that is a virulence factor for hypervirulent Klebsiella pneumoniae. We have biochemically and structurally characterized the aerobactin biosynthetic pathway and have developed an approach to find inhibitors of aerobactin biosynthesis that may be tools to probe the pathway chemically to inhibit growth of this human pathogen.

Education and Training:

  • PhD, Experimental Oncology and Biochemistry, University of Wisconsin (1995)
  • BS, Biochemistry, Brown University (1989)
  • Postdoctoral Fellow, Biochemistry, University of Wisconsin

Employment:

  • Director, PhD Program in Biomedical Sciences, Jacobs School of Medicine and Biomedical Sciences (2020-present)
  • Professor, Structural Biology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2021-present)
  • Director, Natural Sciences Interdisciplinary Master, Jacobs School of Medicine and Biomedical Sciences (2020–2022)
  • Associate Professor, Structural Biology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2018–2021)
  • VP for Research, Hauptman-Woodward Institute (2015–2017)
  • Principal Research Scientist, Hauptman-Woodward Institute (2012–2017)
  • Research Assistant Professor, Structural Biology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2001–2017)
  • Senior Research Scientist, Hauptman-Woodward Institute (2007–2012)
  • Research Scientist, Hauptman-Woodward Institute (2001–2007)
  • Assistant Scientist, Biochemistry, University of Wisconsin (1998–2001)

Research Expertise:

  • Assay Development: We develop approaches to identify chemical probes that block enzyme reactions that can be used to improve our understanding of the role that proteins play in virulence.
  • Enzymology: We use biochemical and structural techniques to identify the mechanisms that proteins use to catalyze critical reactions.
  • Natural Product Biosynthesis: Many microbes use novel enzymes to produce small chemicals that are secreted into the environment and help the producing organism adapt to diverse environments. We use structural, chemical, and biological tools to identify natural products and the pathways for their biosynthesis.
  • Structural Biology: We use x-ray crystallography to determine the molecular structure of important macromolecules that carry out critical biological processes.

Grants and Sponsored Research:

  • April 2020–March 2025
    Structural Studies of Nonribosomal Peptide Synthesis (R35GM136235)
    NIH/NIGMS
    Role: Principal Investigator
  • January 2016–December 2019
    The structural basis for modular nonribosomal peptide synthesis(R01GM116957)
    NIH/NIGMS
    Role: Principal Investigator
  • February 2016–January 2019
    Development of HTP Assay for Inhibitors of Aerobactin Production(R01AI116998)
    National Institutes of Health
    Role: Principal Investigator
  • June 2012–May 2016
    Enzymes involved in production of bacterial isonitrile-containing natural products [1158169].
    National Science Foundation
    Role: Principal Investigator
  • September 2011–October 2014
    Identification of New Drug Targets in Multi-Drug Resistant Bacterial Infections
    Department of Defense (DOD)
    Role: Principal Investigator
    $1,744,854
  • July 2010–June 2014
    Structures of Peptide Synthetases and Related Proteins [NIH(GM069440-06)]
    National Institutes of Health
    Role: Principal Investigator
  • July 2009–June 2010
    Structures of Peptide Synthetases and Related Proteins [NIH(GM069440-S2)]
    National Institutes of Health
    Role: Principal Investigator
  • July 2004–June 2010
    Structures of Peptide Synthetases and Related Proteins [NIH(GM069440)]
    National Institutes of Health
    Role: Principal Investigator
  • November 2008–November 2009
    Development of a small molecule screening capability for structure-based drug design at the Hauptman-Woodward Institute
    Max and Victoria Dreyfus Foundation
    Role: Principal Investigator
  • July 2007–June 2009
    Structure and function studies of Pseudomonas pyoverdine synthesis enzymes [CFF Gulick07I0]
    Cystic Fibrosis Foundation
    Role: Principal Investigator

Patents:

  • Novel Glutathione S-transferase isoforms Mutant forms of mammalian glutathione s-transferase engineered to exhibit higher catalytic efficiency with a anti-cancer agent (2000)

Journal Articles:

See all (80 more)

Professional Memberships:

  • American Society for Biochemistry and Molecular Biology (2018–present)
  • American Crystallographic Association (2000–2016)
  • American Chemical Society (1996–present)
  • American Association for the Advancement of Science (1992–present)

Presentations:

  • "Structural Studies into the Biosynthesis of Bacterial Natural Products." Invited Seminar (2022)
  • "Structural Studies into the Biosynthesis of Bacterial Natural Products." Invited Seminar. Department of Pharmacology and Toxicology, University at Buffalo (2021)
  • "Nonribosomal Peptide Biosynthesis: Studies of a Protein Assembly Line." Invited Seminar, Department of Biology, University at Buffalo (2020)
  • "Structural Studies of Antibiotic Production by Nonribosomal Peptide Synthetases" Invited Seminar, Department of Biochemistry, University of Illinois (2019)
  • "Iron Acquisition in Bacterial Pathogens: Structural and Functional Studies of Siderophore Biosynthesis" Invited Seminar, Dalhousie University (2018)
  • "The Structural Cycle of Nonribosomal Peptide Synthetases." American Society of Pharmacognosy Annual Meeting (2018)
  • "Conformational Changes that Drive the Dynamic Structural Cycle of the Nonribosomal Peptide Synthetases" Directing Biosynthesis V Conference (2017)

Service Activities:

  • Deutsche Forschungsgemeinschaft; Ad hoc Reviewer (2021)
  • ZRG1 F04A (20) Fellowships Review: Chemistry, Biochemistry, and Biophysics A; Grant Review Panel (2020)
  • ZRG1 F04A (20) Fellowships Review: Chemistry, Biochemistry, and Biophysics A; Grant Review Panel (2020)
  • Department of Structural Biology; Director of Graduate Studies (2020–present)
  • Research Foundation Flanders (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, FWO), European Research Foundation, Strasbourg, France; External Reviewer (2020)
  • Co-director of NSIM program; co-Director, Natural Sciences Interdisciplinary Master's (2020–present)
  • Mentor and guide first year PhD students through courses and rotations; Director, PhD Program in Biomedical Sciences (2020–present)
  • NWO Talent Programme Veni, Dutch Research Council, The Hague, The Netherlands.; Grant Review External Reviewer (2020)
  • Journal of Biological Chemistry; Editorial Board Member (2020–present)
  • Swiss National Science Foundation, Bern Switzerland.; Grant Review External Member (2018)
  • Marsden Fund, Royal Society Te Aparangi, New Zealand.; Grant Review External Member (2018)
  • Boeringer Ingelheim Fonds, Mainz, Germany.; Grant Review External Member (2017)
  • National Science Foundation. Chemistry of Life Processes CAREER Proposals; Grant Review Panel Member (2017)

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Contact Information

Jacobs School of Medicine and Biomedical Sciences
955 Main St
Buffalo, New York 14203-1121
Phone: (716)829-3696
amgulick@buffalo.edu