Associate Professor of Pediatrics and Molecular Microbiology

• Infectious Diseases
• Pathobiology
• David B. Haslam Research Lab

Dr. Haslam's laboratory is investigating how bacterial toxins damage human cells and why humans are susceptible to diseases caused by these toxins. Most of these studies are focused on shiga toxin, the agent responsible for hemolytic uremic syndrome in children. This toxin is released by strains of E. coli that commonly colonize domestic animals, and consequently is often associated with food-borne outbreaks. Dr. Haslam's laboratory has found than most animals are resistant to the toxin because they produce an enzyme called Forssman synthetase. This enzyme modifies toxin receptors, making them unavailable for toxin binding. Humans, however, are unable to make this enzyme and consequently have numerous toxin receptors available.

After binding to receptors at the surface of human cells, shiga toxin is transported through the cell via a novel retrograde pathway. The ultimate destination for shiga toxin is the cytoplasm, where it inactivates ribosomes, inhibits protein synthesis, and induces cell death. Dr. Haslam's laboratory recently identified a molecular chaperone that is utilized by shiga toxin to gain access to the cytoplasm. The laboratory is currently investigating the function of this chaperone both in toxin trafficking and in normal cellular biology. It is hoped that by understanding how toxin molecules bind to human cells and find their way to the cytoplasm, treatments may be directed against these steps in toxin-mediated diseases.

Education

• B.S., University of Calgary, 1984
• M.D., University of Calgary Medical School, 1987

Training

• Residency in Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, 1988-91
• Clinical Fellowship, Pediatric Infectious Diseases, Washington University School of Medicine, 1991-92
• Research Fellowship in Molecular Microbiology, Washington University School of Medicine, 1992-95

Licensure and Board Certification

• Missouri license, 1991
• National Board of Medical Examiners
• American Board of Pediatrics, 1994
• Pediatric Infectious Diseases, 1997

Honors

• Senior Pediatric Resident Clinical Teaching Award, University of Ottawa, 1990
• Pediatric Fellow Clinical Teaching Award, House Officers, Washington University School of Medicine, 1992
• Pediatric Scientist Development Program Fellowship Award, 1992-95
• March of Dimes Basil O'Connor Starter Scholar Research Award, 1997-1999
• Young Investigator Award, Pediatric Infectious Diseases Society, 2000
• Burroughs Wellcome Foundation Investigators in Microbial Pathogenesis Award, 2002
• Distinguished Teaching Award. Course leader of "Selective of the Year". Awarded by Washington University Medical Students, 2003
• Outstanding Clinical Teaching Award. Awarded by Washington University Medical Students, 2005

Selected Publications

1. Xu H, Storch T, Yu M, Elliott SE, Haslam DB: Characterization of the human Forssman synthetase gene: An evolving association between glycolipid synthesis and host-microbial interactions. J. Biol. Chem. 1999; 274; 29390-8.

2. Yu M, Haslam RHA, Haslam DB: HEDJ, a novel Hsp40 co-chaperone localized to the endoplasmic reticulum of human cells. J. Biol. Chem. 2000; 275; 24984-92.

3. Elliott SP, Yu M, Xu H, Haslam DB: Forssman synthetase expression results in diminished shiga toxin susceptibility: A role for glycolipids in determining host-microbial interactions. Infect. Immun. 2003; 71(11): 6543-52.

4. Yu M, Haslam DB: Shiga toxin is transported from the endoplasmic reticulum following interaction with the luminal chaperone HEDJ/Erdj3. Infect. Immun. 2005; 73(4): 2524-32.

5. Zhao L and Haslam DB. A quantitative and highly sensitve luciferase-based assay for bacterial toxins that inhibit protein synthesis. J Med Microbiol. 2005; 54: 1023-1030.

6. Saenz J, Doggett TA, and Haslam DB. Identification and characterization of small molecules that inhibit intracellular toxin transport. Infect. Immun. 2007; 75: 4552-61.