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Department of Medicine

Department of Medicine

 Division of Infectious Diseases

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photo Hassan Badrane, PhD

Research Assistant Professor

Email: hab42@pitt.edu

Phone: 412-648-8438

Contact
Office: Scaife Hall, Suite 875
3550 Terrace Street
Pittsburgh, PA 15261
 
Phone: 412-648-8438
Fax: 412-648-8455
E-mail: hab42@pitt.edu
Administrative Assistant:
Tanya Gonzales
Email: tal67@pitt.edu
Phone: 412-648-8510
Education and Training
Education
Ph.D. (Genetics & Microbiology), Pasteur Institute / University Paris XI, FRANCE, 1997
Master Degree (Genetics), University Paris XI, FRANCE, 1990
Certificate in « fundamental virology », Pasteur Institute, FRANCE, 1994
Certificate in « Sequence Analysis & Molecular Evolution », EMBL, Germany, 1993
Certificate in « Genetic Engineering », Pasteur Institute, FRANCE, 1989
Training
Assistant Scientist « Candida albicans molecular and cellular pathogenesis », University of Florida - VA Medical Center, 2003
Postdoc Fellow « DNA-microarrays a powerful tool for systems biology », University of Florida, 2001
Research Fellow « Virus-host interactions using Yeast two-hybrid system », Pasteur Institute, FRANCE, 1999
Postdoc Fellow « Molecular evolution of mating type genes and their function », University of Minnesota, 1997
Ph.D. « Lyssaviruses phylogeny and its immuno-pathological implications », Pasteur Institute, FRANCE, 1991
Research Interest
Dr. Hassan Badrane is investigating opportunistic infections caused by Candida species of yeasts, particularly C. albicans. He is characterizing genes where expression has been found to be induced in vivo and their encoded protein have an immunogenic property. Presumably, these genes will be important during infection. Among them, he characterized IRS4 to encode for an Eps15 homology (EH) domain protein, which regulates the levels of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). This regulation is exerted by activating lnp51p, a 5-phosphatase enzyme that converts PI(4,5)P2 to PI4P. Indeed, mutant strains in which either IRS4 or INP51 has been knocked-out, had higher levels of PI(4,5)P2, which in tum affected the cell wall integrity pathway and hyphal growth, and attenuated virulence to mice in a disseminated candidiasis model. In addition, these mutant strains exhibited abnormal intracellular patches of PI(4,5)P2 that colocalized with septins. Currently, he is deciphering the upstream regulation that controls the function of lrs4p/lnp51p as well as setpins.
Clinical Interest
On the clinical side, Dr. Badrane is looking at the response of C. albicans to drugs, particularly Caspofungin, one of the most used drugs for the treatment of candidiasis. Toward this end he has engineered a reporter in which a Candida optimized GFP or RFP (CaGFP or CaRFP) was fused to a Candida optimized Plekstrin Homology (CaPH) domain or the septin CDC10, respectively. These reporters were co-expressed in C. albicans wild-type strain SC5314. The PH domain is known to specifically bind PI(4,5)P2 in vivo. Using confocal microscopy, he has followed PI(4,5)P2 and septin responses for 3 hours after exposure to caspofungin. Exposure to caspofungin resulted in a highly dynamic co-mislocalization of PI(4,5)P2 and septin, as well as an increase in PI(4,5)P2 intracellular levels, in a dose-dependent manner. Moreover, caspofungin led to a wide mother-daughter bud-neck during cell division, and caused perturbations in septation and cytokinesis. At the present time he is comparing the effect of caspofungin between C. albicans and C. glabrata, and looking at its effect on hyphal growth in C. albicans.
Publications
For my complete bibliography, Click Here.
Selected Publications:
Rama SB, Nguyen MH, Cheng S, Badrane H, Iczkowski KA, Wegener M, Gaffen SL, Mitchell AP, Clancy CJ. A competitive infection model of hematogenously disseminated candidiasis in mice redefines the role of Candida albicans IRS4 in pathogenesis. Infection & Immunty. 2013; 81:5: 1430-8.
Badrane H, Nguyen, JR, Blankenship S, S Cheng, B Hao, AP Mitchell, CJ Clancy. Rapid redistribution of phosphatidylinositol-(4,5)-bisphosphate and septins during the Candida albicans response to caspofungin. Anti-microbial Agents & Chemotherapy. 2012; 56:9: 4614-24.
Badrane H, MH Nguyen, S Cheng, V Kumar, H Derendorf, KA Iczkowski, CJ Clancy. The Candida albicans phosphatase Inp51p interacts with the EH domain protein Irs4p, regulates phosphatidylinositol-4,5-bisphosphate levels and influences hyphal formation, the cell integrity pathway and virulence. Microbiology. 2008; 154:9: 3296-308.
Badrane H, S Cheng, MH Nguyen, HY Jia, Z Zheng, N Weisner, CJ Clancy. Candida albicans IRS4 contributes to hyphal formation and virulence after the initial stages of disseminated candidiasis. Microbiology. 2005; 151:9: 2923-31.
Badrane H, M Nguyen, CJ Clancy. Highly-dynamic and specific phosphatidylinositol-(4,5)-bisphosphate, septin and cell wall integrity pathway responses correlate with caspofungin activity against Candida albicans. Anti-microbial Agents & Chemotherapy. 2016.