U.S. Department of Health and Human Services
About NIDDK
 

 Training & Experience

 

​Ph.D., Purdue University, 1973

M.S., Atlanta University, 1970

B.A., Talladega College, 1964

William G. Coleman Jr., Ph.D.

May 6, 1942 - August 18, 2014
Former Scientific Director, National Institute of Minority Health and Health Disparities (NIMHD)
 

Research Summary

Research Goal

Dr William Coleman's research focused on the understanding of the mechanisms of bacterial pathogenesis and antibiotic resistance of gram-negative bacteria, specifically as they relate to ulcer disease and other bacterial infections.

Research

Dr. William Coleman's research group performed basic research on enzymes responsible for lipopolysaccharide (LPS) synthesis in gram-negative bacteria, utilizing techniques in bacterial genetics, molecular biology, protein chemistry, enzymology, and x-ray crystallography.   The goal was to characteriz​e enzymic processes that have therapeutic implications for human disease.   Research initiatives emphasized the understanding of the structure and function of LPS biosynthetic enzymes, the role of LPS in the pathology of E. coli and Helicobacter pylori, and the evaluation of specific enzymes in the LPS biosynthesis pathway as potential novel antibiotic targets.   L-glycero-D-mannoheptose (heptose) is a 7-carbon sugar present in the lipopolysaccharide of a wide variety of gram-negative bacteria.  Heptose provides a link between lipid A-KDO, the outer core and the O-antigen regions of LPS.  ADP-L-glycero-D- mannoheptose 6-epimerase (epimerase) is required for the synthesis of the heptose precursor, ADP-L-glycero-D-mannoheptose.  Gram-negative bacteria without epimerase activity have the following characteristics:  severely truncated LPS, increased sensitivity to gastric bile and serum killing, hypersensitivity to a number of hydrophobic agents including antibiotics, and decreased pathogenicity.  The essential role of the epimerase in the synthesis of LPS and the ability of gram-negative bacteria to thrive in human hosts makes it an attractive target for antimicrobial agents.  To fully realize the potential of the epimerase as a novel target for therapeutic attack requires detailed knowledge of the structure and catalytic mechanism of this enzyme.  Therefore, Dr. Coleman's research group undertook x-ray crystallographic studies to determine the three-dimension structure and catalytic mechanism of the E. coli K-12 epimerase.  H. pylori plays a major role in gastritis, peptic ulcer disease, and gastric carcinoma.  Although several pathogenic determinants have been proposed, the mechanism of pathogenesis is not yet known.  The group's final studies focused on identifying and characterizing novel targets for the development of antibiotics and protective vaccines directed against H. pylori.
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