Dr. Pablo C. Okhuysen
The University of Texas Health Science Center at Houston
Internal Medicine - Infectious Diseases
School of Public Health
Center for Infectious Diseases
- Human genetics and susceptibility to infectious diseases
- Pathogenesis and host immune response to the enteropathogens Cryptosporidium and enteroaggregative E. coli
The evolutionary pressure that infectious diseases have placed on the human genome is substantial and has undoubtedly contributed over time to the functional variation of the genome. Small variations in the human genome can determine not only susceptibility to infection with a particular pathogen but also can influence the intensity of infection, disease severity and in some instances, long term complications. The laboratory is interested in the identification of variations in human genes that influence the attachment, colonization, recognition by the innate immune system, inflammatory response and the specific acquired immune response to enteropathogens that cause diarrhea. Using a gene-candidate approach in children with endemic diarrhea and in travelers with diarrhea, the laboratory studies how human DNA single nucleotide polymorphisms (SNPs) relate to infection with various enteropathogens and validates their functional relevance to infection in vitro.
Cryptosporidium is a common cause of diarrhea worldwide. This environmentally resistant organism infects the intestinal epithelial membrane of various hosts and localizes to a unique intracellular but extracytoplasmic parasitophorous vacuole. The parasite’s life cycle consists of sexual and asexual stages but cannot be propagated in artificial media. The laboratory is interested in the identification of Cryptosporidium virulence determinants and antigens that are recognized during naturally acquired and experimental infection.
Enteroaggregative E. coli (EAEC) is an emerging enteropathogen that has been associated with acute and persisting diarrhea in children of developing countries and in patients with uncontrolled HIV infection. Recently, EAEC has been identified as a common cause of sporadic diarrhea in US children. In addition, chronic EAEC infection is becoming increasingly associated with neuro-developmental deficits in children of developing countries. The laboratory is interested in developing tools for EAEC identification, understanding the mechanisms by which EAEC attaches to the intestinal epithelium, the role of biofilm in establishing infection and the antigens that are recognized during naturally acquired infection.
During the tutorial trainees will be introduced to research on human genetic variation and susceptibility to infection, methods used to detect virulence determinants and measure host immune response to enteric pathogens.
Flores J, Dupont HL, Paredes-Paredes M, Aguirre-Garcia MM, Rojas A, Gonzalez A, Okhuysen PC. Whole Blood Gamma Interferon Response to Cholera Toxin B Subunit and Resistance to Travelers' Diarrhea. A Pilot Study of Cellular Immune Response in Enterotoxigenic Escherichia coli Associated Diarrhea. Clin Vaccine Immunol. Mar 10. PMID: 20219880
Mohamed JA, DuPont HL, Jiang ZD, Flores J, Carlin LG, Belkind-Gerson J, Martinez-Sandoval FG, Guo D, White AC, Jr., Okhuysen PC. A single-nucleotide polymorphism in the gene encoding osteoprotegerin, an anti-inflammatory protein produced in response to infection with diarrheagenic Escherichia coli, is associated with an increased risk of nonsecretory bacterial diarrhea in North American travelers to Mexico. J Infect Dis. 2009 Feb 15;199(4):477-85. PMID: 19128145
Flores J, Okhuysen PC. Genetics of susceptibility to infection with enteric pathogens. Curr Opin Infect Dis. 2009 Oct;22(5):471-6. PMID: 19633551
Grimes KA, Mohamed JA, Dupont HL, Padda RS, Jiang ZD, Flores J, Belkind-Gerson J, Martinez-Sandoval FG, Okhuysen PC. PCR-based assay using occult blood detection cards for detection of diarrheagenic Escherichia coli in specimens from U.S. travelers to Mexico with acute diarrhea. J Clin Microbiol. 2008 Jul;46(7):2227-30. PMID: 18480224
Flores J, DuPont HL, Lee SA, Belkind-Gerson J, Paredes M, Mohamed JA, Armitige LY, Guo DC, Okhuysen PC. Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico. Clin Vaccine Immunol. 2008 Aug;15(8):1194-8. PMID: 18579697
Flores J, DuPont HL, Jiang ZD, Belkind-Gerson J, Mohamed JA, Carlin LG, Padda RS, Paredes M, Martinez-Sandoval JF, Villa NA, Okhuysen PC. Enterotoxigenic Escherichia coli heat-labile toxin seroconversion in US travelers to Mexico. J Travel Med. 2008 May-Jun;15(3):156-61. PMID: 18494692
Mohamed JA, Huang DB, Jiang ZD, DuPont HL, Nataro JP, Belkind-Gerson J, Okhuysen PC. Association of putative enteroaggregative Escherichia coli virulence genes and biofilm production in isolates from travelers to developing countries. J Clin Microbiol. 2007 Jan;45(1):121-6. PMID: 17093030
Mohamed JA, DuPont HL, Jiang ZD, Belkind-Gerson J, Figueroa JF, Armitige LY, Tsai A, Nair P, Martinez-Sandoval FJ, Guo DC, Hayes P, Okhuysen PC. A novel single-nucleotide polymorphism in the lactoferrin gene is associated with susceptibility to diarrhea in North American travelers to Mexico. Clin Infect Dis. 2007 Apr 1;44(7):945-52. PMID: 17342646