Duke University | Chemical Biology Program

Meet the Chemical Biology Faculty

Chemical Biology utilizes small molecules to probe and manipulate biology, and faculty who make use of the approaches of chemical biology are active in many of the traditional disciplines of biochemistry, including biophysics, mechanistic enzymology, metal ion transport and biochemical signaling and signal transduction. Practitioners of Chemical Biology are also leaders in the development of novel experimental techniques and approaches, including chemical synthesis, structural biology and the development of novel omic technologies.

The faculty of the Program in Chemical Biology hail from various Departments across the School of Medicine and the Faculty of Arts & Sciences. Researchers use a variety of techniques, including chemical synthesis, structural biology, biophysical chemistry, to address a range of problems in biology, including mechanistic enzymology, signaling and signal transduction and metalobiochemistry. Our faculty is constantly evolving, but currently includes:

Professor Lorena Beese (Biochemistry) studies the mechanism of the macromolecular assemblies involved in DNA replication and repair and in cellular signaling. Professor Beese also directs the Center for Structural Biology and the Macromolecular X-ray Crystallography Resource.

James B. Duke Professor Pat Casey (Pharmacology & Cancer Biology) studies cellular signaling modulated by GTP binding proteins and protein lipidation.

Assistant Professor Don Coltart (Chemistry) studies new synthetic methodologies and the use of small molecule probes for the study of cellular signaling, including small molecule inhibitors of protein-protein interaction.

Professor Al Crumbliss (Chemistry) studies metal ion binding and transport in biological systems.

Assistant Professor Kathy Franz (Chemistry) studies the functional consequences of metal ion chelation and coordination in biological systems, along with applications of these systems to medicine.

Associate Professor Tim Haystead (Pharmacology & Cancer Biology) uses high-throughput mass spectrometric approaches to delineate signal transduction pathways and new druggable targets for the treatment of a variety of diseases.

Professor Joe Heitman (Molecular Genetics and Microbiology) studies signaling, especially the transduction cascades relevant to virulence. Professor Heitman is the Director of the Center for Microbial Pathogenesis and the University Program in Genetics and Genomics.

Professor Homme Hellinga (Biochemistry) uses computational and experimental approaches to the de novo synthesis of functional proteins.

Assistant Professor Jiyong Hong (Chemistry) uses small molecule approaches to identify novel genes and their protein products important in developmental biology.

James B. Professor Bob Lefkowitz (Medicine) studies neurotransmission and the action of neurotransmitters. Professor Lefkowitz is an Investigator of the Howard Hughes Medical Institute.

Professor Dewey McCafferty (Chemistry) studies the enzymology of bacterial cell-wall assembly, the enzymology of chromatin, and mechanisms of bacterial virulence.

Glaxo-Wellcome Professor Donald McDonnell (Pharmacology & Cancer Biology) studies the nuclear receptor-mediated signaling processes.

Nanaline Duke Professor Tony Means (Pharmacology & Cancer Biology) studies the regulation of cell cycle and differentiation, especially in the context of oncogenesis. Professor Means is Chair of the Department of Pharmacology and Cancer Biology.

David and Sarah Steadman Professor Chris Newgard (Pharmacology & Cancer Biology) uses metabolomic approaches to study metabolic regulatory processes. Professor Newgard is the Director of the Steadman Nutrition Center at Duke.

George Barth Geller Professor Chris Raetz (Biochemistry) studies the biosynthesis of lipid A, signaling via endotoxin pathways, and the identification and mechanism of novel antibiotics.

Professor Eric Toone (Chemistry) studies biocatalysis and the evolution of new enzyme functions, association in aqueous solution, and the synthesis of novel donors of nitric oxide.

James B. Duke Professor Warren Warren (Chemistry) studies molecular imaging at length scales ranging from molecules to whole animals.

Associate Professor John York (Pharmacology & Cancer Biology) studies inositol signaling pathways in human disease. Professor York is an Investigator of the Howard Hughes Medical Institute.

Assistant Professor Pei Zhou (Biochemistry) uses magnetic resonance approaches to understand molecular recognition in biological systems.

	Signaling and Signal Transduction	Enzymology	Metallobiochemistry
Small Molecule Synthesis	Coltart Hong York	Hong McCafferty Toone	Franz
Omic Technologies	Haystead Heitman McDonnell Newgard	Haystead Newgard
Structural Biology	Beese McDonnell York	Beese Toone Zhou	Beese Crumbliss Franz
Biophysics	Means McDonnell York	Beese McCafferty Toone Warren York	Crumbliss Franz

The emergence of drug-resistant bacteria poses one of the most severe threats to human health, and the search for novel antibiotics is a vital area of research. Professor Christian Ratez has worked for decades to elucidate the enzymatic pathways to lipid A, a crucial component of Gram-negative bacterial lipopolysaccharide. Inhibitors of several of these enzymes might serve as important antibiotics, species that might evade immunity. The image above shows the structure of E. coli LpxA, the enzyme that catalyzes the first step of the pathway. The structure illuminates the structural basis for the lipid specificity of the enzyme as well as the chemical mechanism of catalysis (from Williams and Raetz, Proc. Natl. Acad. Sci. USA 2007, 104, 13543-13550).

Heat map of a series of geranylgeranyltransferase inhibitors colored according to percent similarity using Tanimoto coefficient structural fingerprinting (Yuri Peterson and Professor Pat Casey). The use of visualization tools like this one aids in the rapid development of novel high affinity ligands for a variety of proteins.