Section of Microbial Pathogenesis Seminar series Research in Progress and Thesis Seminars Section Faculty   - Dr. Jorge Galán   - Dr. Hervé Agaisse   - Dr. Norma Andrews   - Dr. Brett Lindenbach - Dr. John MacMicking   - Dr. Walther Mothes   - Dr. Craig Roy Microbiology Graduate Program All Program Faculty Recruitment & Admissions Advisory Committees Courses & Labs Exam & Requirements Student Handbook Student Funding Search this site:		Craig R. Roy  Associate Professor Microbial Pathogenesis Ph.D. Stanford Univ. 1991 email: craig.roy@yale.edu office: (203) 737-2408 lab:    (203) 737-2409 Research Interests The focus of our research is to understand the molecular and cellular events that enable microbial pathogens to evade host defense mechanisms. In particular, we are interested in how bacteria that replicate inside mammalian cells modulate vesicular transport following uptake. We have been using the bacteria Legionella pneumophila and Coxiella burnetii as model pathogens to study this process. L. pneumophila is a facultative intracellular pathogen capable of growing within an endoplasmic reticulum-derived organelle in macrophages and protozoan host cells. C. burnetii is an obligate intracellular pathogen that replicates in an acidic phagolysosomal compartment. Despite residing in completely different subcellular organelles, a highly conserved type IV secretion system is utilized by both L. pneumophila and C. burnetii to modulate host cellular functions. For both organisms, substrate proteins translocated into host cells by this system are believed to be the primary determinants of intracellular fate. We have isolated a number of L. pneumophila substrate proteins and have determined that they target key regulators of the host secretory pathway, facilitating L. pneumophila transport to the endoplasmic reticulum. It is predicted that C. burnetii type IV substrate proteins will target components of the host endocytic pathway. Multidisciplinary approaches are being used to identify and characterize these substrate proteins. Additionally, we are investigating how host innate and adaptive immune responses eventually lead to protection and clearance of these pathogens. Roy Lab Photo. Selected References: Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature. 2007 Nov 15;450(7168):365-9. PDF Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat Cell Biol. 2006 Sep;8(9):971-7. PDF Zamboni DS, Kobayashi KS, Kohlsdorf T, Ogura Y, Long EM, Vance RE, Kuida K, Mariathasan S, Dixit VM, Flavell RA, Dietrich WF, Roy CR. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat Immunol. 2006 Mar;7(3):318-25. PDF Nagai H, Cambronne ED, Kagan JC, Amor JC, Kahn RA, Roy CR. A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc Natl Acad Sci U S A. 2005 102(3):826-31. PDF Kagan JC, Stein MP, Pypaert M, Roy CR. Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle. J Exp Med. 2004 199(9):1201-1211. PDF Neild, A.L. and C.R. Roy. Legionella reveal dendritic cell functions that facilitate selection of antigens for MHC class II presentation. Immunity 2003 18(6): p. 813-823. PDF Kagan, J.C. and C.R. Roy. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol. 2002 4(12): p. 945-54. PDF Nagai, H, J.C. Kagan, X. Zhu, R.A. Kahn and C.R. Roy. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science. 2002 295: p. 679-82. PDF Nagai H. and C.R. Roy The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. EMBO J. 2001 20(21): p. 5962-5970. PDF Coers, J., C.M. Monahan, C.R. Roy. Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth. Nature Cell Biology 1999 Nov;1(7):451-453. PDF
Yale University School of Medicine Boyer Center for Molecular Medicine Section of Microbial Pathogenesis 295 Congress Ave. New Haven, CT 06536-0812 USA
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