BBS Faculty Member - Matthew Waldor

Matthew Waldor

Department of Medicine

Brigham and Women's Hospital
Channing Laboratory and HHMI
181 Longwood Avenue
Boston MA 02115
Tel: 617-525-4646
Fax: 617-525-4660
Email: mwaldor@rics.bwh.harvard.edu
Lab Members: 7 postdoctoral fellows, 2 graduate students, 2 research associates



We are exploring the evolution, pathogenicity, and cell biology of clinically important enteric pathogens including Vibrio cholerae, Vibrio parahaemolyticus and enterohemorrhagic Escherichia coli (EHEC).

Major on-going projects include:

I. Bacterial cell polarity. The cell poles constitute a key subcellular domain that is often critical for motility, chemotaxis and chromosome segregation in rod-shaped bacteria. Using a combination of fluorescence microscopy and genetic and biochemical approaches, we are exploring the processes that underlie the formation, recognition and perpetuation of the pole domain in vibrios.

II. sRNA control of virulence. Small untranslated RNAs (sRNAs) regulate many cellular processes in non-pathogenic E. coli. Hfq is an RNA binding protein that is important for the activity of many sRNAs. We found that
V. cholerae and EHEC lacking Hfq are attenuated in virulence, suggesting that sRNAs, in conjunction with Hfq, control processes that are critical for their pathogenicity. We are investigating the targets and mechanisms of action of several sRNAs identified using bioinformatics or by deep sequencing approaches.

III. Use of infant rabbit models of diarrheal disease to study host-pathogen interactions. Studies of the biology of enteric pathogens during infection have been hampered by the lack of non-surgical small animal models of diarrheal disease. We found that infant rabbits orally inoculated with EHEC,
V. cholerae or V. parahaemolyticus develop diarrheal diseases that mimic the respective human infections. We are taking advantage of these models to gain insights into bacterial physiology during growth in the host as well as host-pathogen interactions.

IV. D-amino acids in bacterial physiology. We found that diverse bacteria release a variety of D-amino acids. We are studying the mechanisms by which released D-amino acids control cell wall metabolism and cell shape.

V. Applying single molecule real time DNA sequencing to assess the extent, diversity and functional consequences of DNA modifications (e.g. methylation) in enteric pathogens.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Ritchie JM, Rui H, Zhou X, Iida T, Kodoma T, Ito S, Davis BM, Bronson RT, Waldor MK. Inflammation and disintegration of intestinal villi in an experimental model for Vibrio parahaemolyticus-induced diarrhea. PLoS Pathog 8(3):e1002593, 2012

Ringgaard S, Schirner K, Davis BM, Waldor MK. A family of ParA-like ATPases promotes cell pole maturation by facilitating polar localization of chemotaxis proteins.
Genes Dev 25:1544-55, 2011.

Chin CS, Sorenson J, Harris JB, Robins WP, Charles RC, Jean-Charles RR, Bullard J, Webster DR, Kasarskis A, Peluso P, Paxinos EE, Yamaichi Y, Calderwood SB, Mekalanos JJ, Schadt EE, Waldor MK. The origin of the Haitian cholera outbreak strain.
N Engl J Med 364:33-42, 2011.



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