Richard L. Guerrant, MD
Graduate School: University of Virginia
Primary Appointment: Professor, Medicine, Infectious Diseases and International Health
Recognition, Diagnosis, Pathogenesis, Impact, Treatment and Prevention of Enteric Infections; Global Health and Tropical Infectious Diseases
Email Address: email@example.com
Building on a background of work defining the unique, prolonged activation of adenylate cyclase by cholera toxin and E. coli LT (1971-1972), the development of the CHO cell assay for cholera toxin and E. coli LT (1974-1976), and the discovery that particulate guanylate cyclase is activated by E. coli ST (1978-1981) and on field work defining the magnitude of diarrheal diseases and their nutritional impact in rural and urban communities in Northeast Brazil (1978-present), Guerrant's laboratory is focused on the recognition, diagnosis, pathogenesis, impact, treatment and prevention of enteric infections. This work includes active studies of the roles of host and microbial genetics, ApoE4 (protection), enteric cytokines and neutrophils and the neutrophil marker lactoferrin in pathogenesis and diagnosis as well as of zinc and glutamine derivatives in the repair of disrupted intestinal barrier function.
Guerrant's research with Drs. Cirle Warren and Laurie Archbald-Pannone on the leading cause of hospital-acquired diarrhea, Clostridium difficile, shows a key role for PLA2, PAF and COX-2 in the secretory and inflammatory effects of C. difficile toxin A, and of adenosine A2a-agonitt, A2b antagonists, PPAR-?, ApoE-peptides, zinc and alanyl-glutamine in preventing inflammation or secretion in animal models of enteric infections. Current work involves animal model, tissue culture, and clinical studies of the roles of these mediators in inflammatory, parasitic (Cryptosporidium) and microbial adhesion or toxin-induced (ex. enteroaggregative E. coli, C. difficile, cholera) diarrheas.
Work with colleagues at the Federal University of Ceara in Fortaleza, Brazil, supported by a current NIH International Collaboration for Infectious Diseases Research (ICIDR) award in its 21st year, shows new and emerging pathogens to be leading causes of persistent diarrhea: enteroaggregative E. coli, Cryptosporidium and perhaps Giardia. In addition, Cryptosporidium and other persistent diarrheas disrupt intestinal barrier function (as determined by lactulose:mannitol permeability) and lead to substantial increased diarrhea burdens for extended periods thereafter in young children. Having recently shown an apparent role for leukocytes (with fecal lactoferrin) in cryptosporidial and enteroaggregative E. coli persistent diarrheas, current work includes studies of the roles of cytokines in intestinal barrier disruption and secretion in bacterial and parasitic diarrheas.
Most important, with colleagues in Brazil, Guerrant has shown that early childhood diarrhea and enteric infections have a lasting impact on growth and cognitive development, more than doubling the global diarrhea DALYs (disability-adjusted life years lost). Current work involves in-vitro, animal model and field studies of mechanisms, genetics (including APOE polymorphisms) and micronutrient interventions to ameliorate these effects. Having also recently demonstrated in collaborative studies that glutamine (the major bowel enterocyte energy source) and its new stable derivatives enhance intestinal sodium absorption at least as well if not better than glucose, current studies are addressing the roles of these compounds and micronutrients in speeding the repair of intestinal barrier functions oral rehydration and repair therapy (ORRT) and hence improving child development and also absorption of antiretroviral drugs in collaborative studies at Virginia, Haiti, South Africa and in Brazil. This work also involves collaborations with Drs. Glynis Kolling, Martin Wu and Michael Timko to examine normal and probiotic flora and to engineer Arg-Gln derivatives into edible plants or probiotic bacteria.
Roche JK, Rojo AL, Costa LB, Smeltz R, Manque P, Woehlbier U, Bartelt L, Galen J, Buck G, Guerrant RL. Intranasal vaccination in mice with an attenuated Salmonella enterica Serovar 908htr A expressing Cp15 of Cryptosporidium: Impact of malnutrition with preservation of cytokine secretion. Vaccine. 2012 Dec 16. doi:pii: S0264-410X(12)01759-8. 10.1016/j.vaccine.2012.12.007. [Epub ahead of print]
Guerrant RL, Deboer MD, Moore SR, Scharf RJ, Lima AA. The impoverished gut-a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. 2012 Dec 11. doi: 10.1038/nrgastro.2012.239. [Epub ahead of print]
Li Y, Figler RA, Kolling G, Bracken TC, Rieger J, Stevenson RW, Linden J, Guerrant RL, Warren CA. Adenosine A2A receptor activation reduces recurrence and mortality from Clostridium difficile infection in mice following vancomycin treatment. BMC Infect Dis. 2012 Dec 10;12:342. doi: 10.1186/1471-2334-12-342.
Kosek M, Haque R, Lima A, Babji S, Shrestha S, Qureshi S, Amidou S, Mduma E, Lee G, Yori PP, Guerrant RL, Bhutta Z, Mason C, Kang G, Kabir M, Amour C, Bessong P, Turab A, Seidman J, Olortegui MP, Lang D, Gratz J, Miller M, Gottlieb M; for the MAL-ED network. Fecal Markers of Intestinal Inflammation and Permeability Associated with the Subsequent Acquisition of Linear Growth Deficits in Infants. Am J Trop Med Hyg. 2012 Nov 26. [Epub ahead of print]
Warren CA, Opstal EJ, Riggins MS, Li Y, Moore JH, Kolling GL, Guerrant RL, Hoffman PS. Vancomycin Treatment's Association with Delayed Intestinal Tissue Injury, Clostridial Overgrowth and Recurrence of Clostridium difficile Infection in Mice. Antimicrob Agents Chemother. 2012 Nov 12. [Epub ahead of print]
DeBoer MD, Lima AA, Oría RB, Scharf RJ, Moore SR, Luna MA, Guerrant RL. Early childhood growth failure and the developmental origins of adult disease: do enteric infections and malnutrition increase risk for the metabolic syndrome? Nutr Rev. 2012 Nov;70(11):642-53. doi: 10.1111/j.1753-4887.2012.00543.x. Review.
Viladomiu M, Hontecillas R, Pedragosa M, Carbo A, Hoops S, Michalak P, Michalak K, Guerrant RL, Roche JK, Warren CA, Bassaganya-Riera J. Modeling the role of peroxisome proliferator-activated receptor γ and microRNA-146 in mucosal immune responses to Clostridium difficile. PLoS One. 2012;7(10):e47525. doi: 10.1371/journal.pone.0047525. Epub 2012 Oct 11.
Warren CA, Li Y, Calabrese GM, Freire RS, Zaja-Milatovic S, van Opstal E, Figler RA, Linden J, Guerrant RL. Contribution of adenosine A(2B) receptors in Clostridium difficile intoxication and infection. Infect Immun. 2012 Dec;80(12):4463-73. doi: 10.1128/IAI.00782-12. Epub 2012 Oct 8.
|Office Address:||Carter Harrison Building, MR-6 , Room 2526|