Overview
Our research interests are broadly based in chemical biology, mechanistic enzymology and molecular medicine. Towards this end our group is engaged in understanding the chemical and kinetic mechanisms, substrate specificity and therapeutic importance of enzymes that posttranslationally modify chromatin, such as histone deacetylases, histone demethylases, histone methyl transferases, and chromatin assembly and remodeling complexes. Building on a mechanistic foundation, our laboratory is also interested in the design, chemical synthesis and evaluation of small molecules to modulate the activity of chromatin modifying enzymes within living cells. This work has recently led to the discovery of histone deamethylases as potential targets for anti-depression therapy. In addition, our laboratory also works to identify and develop novel strategies to overcome bacterial resistance to antibiotics through mechanistic characterization of enzymes involved in bacterial virulence, peptidoglycan biosynthesis, and teichoic acid biosynthesis. A central component of this research is the identification of novel anti-virulence chemotherapeutics and antibiotics capable of overcoming infections from antibiotic resistant bacteria. Our group also works to decode the molecular mechanisms of enzymes involved in mechanistically intriguing reactions from antibiotic natural product biosynthesis. Lastly, our group is working to develop a functional view of the molecular underpinning of initial signaling events in bacterial-induced inflammation, and in turn lay the foundation for the discovery and design of novel small molecule inhibitors of Crohn's disease, ulcerative colitis and related inflammatory bowel disorders.
Current Appointments & Affiliations
Professor of Chemistry
·
2006 - Present
Chemistry,
Trinity College of Arts & Sciences
Member of the Duke Cancer Institute
·
2006 - Present
Duke Cancer Institute,
Institutes and Centers
Recent Publications
Chemoproteomic-enabled characterization of small GTPase Rab1a as a target of an N-arylbenzimidazole ligand's rescue of Parkinson's-associated cell toxicity.
Journal Article RSC chemical biology · January 2022 The development of phenotypic models of Parkinson's disease (PD) has enabled screening and identification of phenotypically active small molecules that restore complex biological pathways affected by PD toxicity. While these phenotypic screening platforms ... Full text CiteInhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.
Journal Article FEBS letters · December 2021 Chlamydia trachomatis, an obligate intracellular bacterium with limited metabolic capabilities, possesses the futalosine pathway for menaquinone biosynthesis. Futalosine pathway enzymes have promise as narrow-spectrum antibiotic targets, but the activity a ... Full text Open Access CiteSmall Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.
Journal Article ACS chemical neuroscience · November 2021 Disrupted cellular trafficking and transport processes are hallmarks of many neurodegenerative disorders (NDs). Recently, efforts have been made toward developing and implementing experimental platforms to identify small molecules that may help restore nor ... Full text CiteRecent Grants
Chemical Biology of the E3 Ubiqutin Ligase Nedd4
ResearchPrincipal Investigator · Awarded by National Institute of General Medical Sciences · 2023 - 2027Pharmacological Sciences Training Grant
Inst. Training Prgm or CMEPreceptor · Awarded by National Institutes of Health · 2020 - 2025Non-Opioid Post-Operative Pain Management Using Bupivicaine-loaded Poly(ester urea) Mesh
ResearchPrincipal Investigator · Awarded by 21MedTech, LLC · 2021 - 2023View All Grants
Education, Training & Certifications
University of North Carolina, Chapel Hill ·
1995
Ph.D.
North Carolina State University ·
1990
B.S.