University of Pittsburgh

Neil Clancy, M.D.

Dr. Cornelius J. (Neil) Clancy is Associate Professor of Medicine and Director of the Mycology Program at the University of Pittsburgh Division of Infectious Diseases. Dr. Clancy’s research interests are in medical mycology, molecular pathogenesis of fungal infections, clinical application of antifungal susceptibility testing, and pharmacokinetics/pharmacodynamics (PK/PD) of antifungal agents. He received the Infectious Diseases Society of America (IDSA) Pfizer Fellowship in Medical Mycology Award in 2000-2001 and an NIH KO8 Clinician Scientist Career Development Award to investigate the molecular pathogenesis of Candida infections. His research is currently funded by the NIH, Veterans Administration Merit Program and a Career Investigator Award from the American Lung Association. In molecular biology, Dr. Clancy was among the first to develop a genomic-scale strategy to identify C. albicans genes expressed in vivo. Using antibodies in the sera of patients with candidiasis to screen a genomic expression library, he identified over 60 genes encoding reactive antigens, including several novel virulence determinants. In studies of SET1 and IRS4/INP51, he was the first to study the roles of histone methylation and phosphoinositide regulation, respectively, in the pathogenesis of candidiasis. In a related translational project, Dr. Clancy recently showed that IgG responses against 15 recombinant proteins identified by screening accurately discriminated candidemic patients from controls, suggesting that antibody and/or antigen detection might facilitate earlier diagnoses. He has expanded his antibody screening research to identify Aspergillus fumigatus antigens. In his PK/PD work, Dr. Clancy was among the first to establish correlations between susceptibility of Candida bloodstream isolates and responses to antifungal therapy, work that was instrumental in validating the utility of susceptibility testing, which is now widely used by clinicians.

Dr. Clancy has published over 50 articles, written several textbook chapters, and received numerous national awards, including 5 IDSA fellowship citations for excellence, the IDSA Fellowship in Medical Mycology, and an IDSA Program Choice Award for research excellence. He has mentored several graduate students, post-docs and fellows, and received a University of Florida teaching award prior ot relocating to the University of Pittsburgh.

Hong-Ming Nguyen, M.D.

Dr Minh-Hong Nguyen is Professor of Medicine and Directors of the Transplant Infectious Diseases Unit and Antimicrobial Management Program at the University of Pittsburgh. She oversees a team of six physicians, three pharmacists and a data analyst in the clinical care and research of infectious diseases in immunocompromised hosts. Her Transplant Infectious Diseases Clinical and Translational Research Unit is comprised of three nurse coordinators, a statistician, and a lab technician.

Dr. Nguyen is recognized in several areas of research: clinical mycology, antifungal pharmacokinetics/pharmacodynamics (PK/PD), fungal diagnostics, animal models of candida infections, and molecular mycology. Her work has been funded since 2000 by the NIH, and she was the recipient of a VA Advanced Research Career Development Award earlier in her career.

Among her seminal clinical reports, Dr. Nguyen was among the first to describe the emergence of non-C. albicans species and antifungal drug-resistance during systemic candidiasis after the introduction of azole drugs. Her multi-center study of candidemia in which these phenomena were described foretold similar results throughout the world in subsequent years, and her observations had major implications for patient outcomes and treatment strategies. Her findings were the basis for her earliest bench research on antifungal susceptibility testing as a fellow and young faculty member. In this work, she showed correlations between in vitro susceptibility to amphotericin B and fluconazole and the response to therapy among patients with candidemia, work that was essential to the development of interpretive breakpoints by the Clinical Laboratory Standards Institute. Her research played a major role in the validation of antifungal susceptibility testing in clinical practice. After the development and widespread introduction of antifungal susceptibility testing, the most pressing need in clinical medical mycology has become the development of improved fungal diagnostics. Despite the importance of fungal infections in modern medicine, current diagnostic tests are limited by both poor sensitivity and specificity. Dr. Nguyen’s research has been at fore in developing novel diagnostic strategies. She clarified the role of galactomannan testing of BAL fluid for the diagnosis of invasive pulmonary aspergillosis, demonstrating its utility in transplant recipients but showing it to offer no advantages over existing tests in non-immunosuppressed hosts. She also showed that antibody responses against a novel Candida antigen panel developed in her lab accurately identified patients with invasive candidiasis, an observation that has revived interest in antibody and/or antigen detection for candidiasis. This project also forms a component of the Mycology Research Unit Program Project, an NIH PO1 for which she is the PI.

Dr Nguyen’s basic research is centered upon the interaction between fungi, in particular Candida albicans, and the infected host. In this context, she has adopted mouse models of candida colonization, mucosal infection, and disseminated infection to study the pathogenesis of candidiasis. Using these models, she has characterized the evolution of C. albicans adaptive responses to stressful in vivo environments, demonstrating that respiration is depressed and oxidative phosphoylation is uncoupled. This response results in diminished susceptibility to antifungal agents, allows the organism to achieve high concentrations within end organs but does not result in damage to the host. She has subsequently showed that immunization with the respiratory mutants was not protective against subsequent challenge with wild-type C. albicans. She is currently characterizing differences in the cell walls of protective and non-protective strains, in order to identify targets for novel vaccine development. In other follow-up experiments, she identified C. albicans DNA damage response genes expressed in response to the host environment during the course of candidiasis. By creating and testing RFX damage response gene mutant strains in her murine models, she has implicated these genes as important contributors to various stages in the pathogenesis of candidiasis.

In an alternative approach to characterizing the host-pathogen interaction, Dr. Nguyen adapted In Vivo Induced Antigen Technology (IVIAT), a novel antibody-based screening method, to identify over 60 C. albicans genes encoding immunogenic proteins during human candidiasis. She demonstrated that seven of these genes make previously unrecognized contributions to the pathogenesis of different types of candidiasis by testing mutant strains in her mouse models. Of note, several of these genes are involved in stress responses, thereby directly linking the results from this line of investigation to the studies described in the previous paragraph. In addition to providing insights into pathogenesis, the proteins identified by antibody screening formed the basis for the diagnostic Candida antigen panel mentioned above.