Andrew M. Gulick PhD

Andrew Gulick

Andrew M. Gulick
PhD

Associate Professor

Department of Structural Biology

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Microbial Pathogenesis; Microbiology; Protein Function and Structure; Proteins and metalloenzymes; Structural Biology; X-ray Crystallography

Contact Information
Jacobs School of Medicine and Biomedical Sciences
955 Main St
Buffalo, NY 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:

  • Associate Professor, Structural Biology, University at Buffalo (2018-present)
  • VP for Research, Hauptman-Woodward Institute (2015–2017)
  • Principal Research Scientist, Hauptman-Woodward Institute (2012–2017)
  • Research Assistant Professor, Structural Biology, University at Buffalo (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.

UB 2020 Strategic Strengths:

  • Molecular Recognition in Biological Systems and Bioinformatics

Grants and Sponsored Research:

  • 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 (61 more)

Professional Memberships:

  • American Crystallographic Association (2000–present)
  • American Chemical Society (1996–present)
  • American Association for the Advancement of Science (1992–present)

School News:

In the Media:


Clinical Specialties:

Clinical Offices:

Insurance Accepted:



Contact Information

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