• Primary Faculty Profiles
• Adjunct Faculty Profiles
• Crane, John, M.D., Ph.D., Assistant Professor
• Genco, Robert, Ph.D., Distinguished Professor
• Gill, Steven, Ph.D.
• Knight, Paul, M.D. and Ph.D., Professor
• Lesse, Alan, Ph.D., Professor
• Murphy, Timothy, Ph.D., Professor
• O'Brian, Mark, Ph.D., Professor
• Rittenhouse-Olson, Kate, Ph.D., Associate Professor
• Russo, Thomas, Ph.D., Assistant Professor
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

---

Education:

1984, M.D., Univ. of Virginia, Charlottesville, VA
1983, Ph.D., Univ. of Virginia, Charlottesville, VA
1977, Bachelor of Science, Cornell University, ithaca, NY

---

Research Interests:

Research in my lab is focussed on diarrrhea-producing strains of Escherichia coli.  Although in the past I worked mostly on enterotoxigenic E. coli (ETEC), more recently I have turned to enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC).  EPEC is a common cause of prolonged watery diarrhea in children in developing countries.  EHEC, which includes notorious strain O157:H7,  causes occasional outbreaks of diarrhea that may become bloody and may be complicated by kidney failure, brain damage, and even death.  Right now there are 2 main projects that I am working on:

1.  Effect of host-derived adenosine as a virulence regulator in EPEC.  EPEC-induced cell death releases ATP from host intestinal cells, and the extracellular ATP is broken down to ADP, AMP, and adenosine.  Adenosine has potent effects on the intestinal cells, including fluid and mucus secretion, and anti-inflammatory effects, but recently we discovered that adenosine has strong effects on the EPEC bacteria themselves, including promotion of growth, changes in the pattern of adherence, decreases in expression of some virulence factors (such as the bundle-forming pilus, BFP), and increases in the expression of other virulence factors (such as the EPEC secreted proteins, or Esps).   Preliminary data suggests that adenosine has some similar effects on EHEC strains as well.   Future goals are to define how adenosine acts on the bacteria, extend our work to EHEC, and to develop adenosine analogs as virulence inhibitors of EPEC and EHEC. 

2.  Effect of zinc in EPEC and EHEC infection.  Zinc has wide-reaching anti-virulence effects in EPEC and EHEC bacteria. Zinc inhibits adherence, expression of adhesins, Esps, and also strongly inhibits Shiga toxin production from EHEC strains.  These findings are interesting because in the past all the beneficial effects on zinc in diarrheal diseases have been attributed to effects on the host.  Our work shows that zinc can affect the pathogen as well, meaning that zinc deficiency would not be necessary for a person to benefit from zinc supplementation.  Future goals include determine how zinc inhibits virulence factor expression, and more studies in animals to see if zinc can block Shiga toxin production, and Shiga-toxin-mediated kidney damage, in vivo in EHEC infection.  For the work on zinc  I collaborate with Dr. Edgar C. Boedeker, Univ of New Mexico, Albuquerque, NM.

Relevant references:

1.  Crane J, Choudhari S, Naeher T, Duffey M. Mutual enhancement of virulence by enterotoxigenic and enteropathogenic Escherichia coli. Infect. Immun. 2006;74:1505-1515.

2.  Crane J, Hoque K. Zinc for infectious diarrhea in developed countries:  should we be sprinkling our own lawns? J. Pediatric Gastroenterol. Nutrit. 2008;46:1-2.

3.  Crane J, Naeher T, Choudhari S, Giroux E. Two pathways for ATP release from host cells in enteropathogenic Escherichia coli infection. Am. J. Physiol. Gastrointest. Liver Physiol. 2005;289:G407-G417.

4.  Crane J, Naeher T, Shulgina I, Zhu C, Boedeker E. Effect of zinc in enteropathogenic Escherichia coli infection. Infect. Immun. 2007;75:5974-5984.

5. Crane J, Shulgina I, Naeher T. Ecto-5'-nucleotidase and Intestinal Ion Secretion by Enteropathogenic Escherichia coli. Purinergic Signalling 2007;3:233-246.