Department of Medicine
University of Pittsburgh
Research
The Division of Infectious Diseases has many productive research laboratories. You can learn more about these laboratories, including their projects and personnel, by clicking any of the laboratory name links below.
Ambrose Laboratory |
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It is estimated that over 30 million people worldwide are infected with HIV-1. Although HIV-1 can be effectively suppressed with current antiretroviral therapy, it is not eradicated from the body. Most HIV+ individuals who stop suppressive therapy have a rapid rebound in plasma viremia, which is most likely due to the persistence of the virus in long-lived reservoirs. These reservoirs may be maintained by low level, ongoing HIV-1 replication in tissues that is not effectively blocked by currently used antiretroviral regimens. The anatomical locations and cell types for these persisting viral reservoirs in infected hosts have not been identified. The Ambrose laboratory uses in vivo and in vitro models to study viral persistence. The RT-SHIVmne macaque model of suppressive antiretroviral therapy is being used to identify the cellular reservoirs of viral persistence. Understanding viral reservoirs should provide valuable information on the location of persisting virus in the body and will facilitate development of new strategies to target appropriate tissues and cells to attempt to eradicate HIV-1 from infected individuals.
The development of drug resistant HIV-1 is a major problem and can arise with all currently used treatment regimens. Despite this, the origin, evolution, and persistence of drug resistance in blood and different tissue compartments are not well understood. The Ambrose laboratory is studying viral diversity and variability, particularly drug resistance-conferring mutations, in different tissues from infected macaques before, during, and after therapy. This may identify the nature and dynamic properties of persistent viral reservoirs in ways that are not possible to perform in people. Understanding how these reservoirs arise and are established by both wild-type and drug resistant viral variants may help determine better strategies for treating HIV-infected individuals, particularly those harboring and potentially transmitting drug resistant virus.
Macrophages have been suggested to contribute to persisting viral reservoirs in vivo. However, less is known about HIV-1 infection of these cells, although it appears to differ from the T lymphocyte infection pathway in many respects. Also, the role of host cell proteins in the HIV-1 lifecycle is poorly understood and is the topic of much investigation in the field. The Ambrose laboratory is investigating the differences between HIV-1 infection of macrophages vs. CD4+ T cells, both critical cell types infected in the host. We hope by elucidating these differences, we can eventually exploit these pathways with novel antiretroviral strategies.
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Zandrea Ambrose, Ph.D. Assistant Professor of Medicine 800 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Email: ambrosez@dom.pitt.edu Phone: 412-624-0512 Fax: 412-648-8512 |
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Tamera Kirkland Ambrose Lab 800 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-9881 Fax: 412-648-8521 Email: kirklandt@dom.pitt.edu |
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Jean Ndjomou, PhD Ambrose Lab S810 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8396 Fax: 412-648-8521 Email: ndjomouj@pitt.edu |
Mission Statement: To investigate novel mechanisms of antimicrobial resistance in Gram-negative pathogens.
Infections due to antimicrobial resistant Gram-negative pathogens continue to pose substantial threat to human well-being. Once thought to be nosocomial, these pathogens are now emerging among non-nosocomial patients including those purely from the community. We are currently conducting several research projects, as outlined below, to elucidate how they acquire resistance to various classes of antimicrobials and what features distinguish them from others.
- Epidemiology of extended-spectrum beta-lactamases (ESBLs) and AmpC-type beta-lactamases in Escherichia coli strains from the community and hospitals.
- Genetic and kinetic characterization of novel AmpC-type beta-lactamases with unique substrate profiles.
- Investigation of 16S ribosomal RNA methylase-mediated aminoglycoside resistance.
- Epidemiology of antimicrobial resistance genes in Acinetobacter baumannii.
- Characterization of mechanisms that lead to colistin resistance.
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Yohei Doi, PhD Assistant Professor of Medicine S829 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9445 Fax: 412-648-8455 Email: yod4@dom.pitt.edu |
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Jennifer Adams-Haduch Paterson and Doi Labs S872 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9904 Fax: : 412-648-8455 Email: adamsj@dom.pitt.edu |
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Tian Guobao Doi and Paterson Labs S839 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-8141 Fax: 412-648-8455 Email: tiang@pitt.edu |
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Obi (Ezenwa) Onuoha S835 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9904 Fax: 412-648-8455 Email: oeo3@pitt.edu |
The focus of our laboratory is on defining genomic characteristics of emerging pathogens. Our research is multidisciplinary and draws upon the tools of genomics, molecular virology, and computational biology. Projects include the study of RNA virus evolution and emergence, the discovery of new retroelements in parasite genomes, and the characterization of endosymbiotic host-parasite interactions.
Please visit our website to read more...
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Elodie Ghedin, PhD Assistant Professor of Medicine S830 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-5850 Fax: 412-383-5851 Email: ghedine@dom.pitt.edu |
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Jay DePasse Ghedin Lab S838 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-5355 Fax: 412-383-5851 Email: depassej@dom.pitt.edu |
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Adam Fitch Ghedin lab S838 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-5355 Fax: 412-383-5851 Email: fitcha@dom.pitt.edu |
The mission of the Public Heath Infectious Disease Laboratory (PHIDL), a component of the Infectious Diseases Epidemiology Research Unit, is to improve and conduct molecular epidemiologic investigations of nosocomial and community acquired bacterial infections. This includes the development of automated, objective and highly discriminatory genotyping methods and research on the genetic basis of disease pathogenesis in several important nosocomial and community-acquired pathogens. Ongoing PHIDL projects include: 1) investigation of Clostridium difficile transmission within hospitals by multi-locus variable number tandem repeat analysis (MLVA) and molecular characterization of toxin production from an emergent hypervirulent clone; 2) molecular surveillance of Neisseria meningitidis and genetic characterization of antigenic variants causing invasive meningococcal disease; 3) molecular epidemiologic investigation of integron-associated multi-drug resistant non-typhoidal Salmonella. The laboratory employs a variety of molecular methods including pulsed field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and MLVA to determine the genetic relationships among bacteria and identify potential outbreaks. In this regard, PHIDL supports the UPMC Infection Control Unit to perform molecular genotyping of potential hospital acquired infections. In addition, PHIDL provides training in molecular epidemiology to masters and doctoral students, infectious diseases fellows, and visiting international scientists.
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Lee Harrison, MD Professor of Medicine and Director of ID Epidemiology Research 521 Parran Hall 130 DeSoto Street Pittsburgh, PA 15261 Phone: 412-624-3332 Fax: 412-624-2256 Email: lharriso@edc.pitt.edu Assistant: Joyce Snyder Asst Phone: 412-624-3137 Asst Email: snyderj@edc.pitt.edu |
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Scott Curry, MD Clinical Assistant Professor Harrison Lab 3550 Terrace Street S865 Scaife Hall Pittsburgh, PA 15261 Phone: 412-648-9704 Fax: 412-648-8455 Email: currysr@dom.pitt.edu |
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Jessica Gee Research Specialist Harrison Lab 861 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412.648-9845 Fax: 412- 648-8455 Email: jlg135@pitt.edu |
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Tatianna Henderson S861 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9704 Fax: 412-648-8455 Email: tkh11@pitt.edu |
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Mary Krauland, PhD Harrison Lab 3550 Terrace Street S865 Scaife Hall Pittsburgh, PA 15261 Phone: 412-648-9704 Fax: 412-648-8455 Email: mgk8@pitt.edu |
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Angela Linn PA Dept of Health Project Administrator Harrison Lab 3A Falk 3601 Fifth Avenue Pittsburgh, PA 15213 Phone: 412-648-6556 Fax: 412-648-6399 Email: arl61@pitt.edu |
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Jane W. Marsh, PhD Research Assistant Professor Harrison Lab 3550 Terrace Street S869 Scaife Hall Pittsburgh, PA 15261 Phone: 412-648-3102 Fax: 412-648-8455 Email: marshj@dom.pitt.edu |
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Mary O'Leary Harrison Lab 3550 Terrace Street S865 Scaife Hall Pittsburgh, PA 15261 Phone: 412-648-9704 Fax: 412-648-8455 Email: olearym@dom.pitt.edu |
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Emily Rictotta Research Specialist Harrison Lab S865 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9704 Fax: 412-648-8455 Email: eer16@pitt.edu |
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Jo-Anne Salangsang Instructor of Medicine Harrison Lab 861 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Fax: 412-648-6399 Email: burgejs@upmc.edu |
The goal of our research is to find the most effective ways to prevent and treat HIV-1 infection. This includes the discovery, preclinical and clinical evaluation of new antiretroviral compounds. Drug resistance has developed to most antiretrovirals and can lead to treatment failure, clinical disease progression and death. Drug resistance may also reduce the effectiveness of antiretrovirals used for HIV-1 prevention. Effective strategies are needed to prevent the emergence of drug-resistant HIV and to treat patients in whom drug-resistant virus has developed. Our laboratory characterizes drug resistance mechanisms at the clinical, virologic, biochemical and structural level and applies this information to the design of new antiretrovirals to minimize the emergence of drug resistance. A new effort of the laboratory is to determine the mechanisms of HIV-1 persistence on antiretroviral therapy, including characterizing the anatomical and cellular reservoirs of persistent HIV and strategies to reduce or eliminate these reservoirs. To accomplish these goals, our laboratory is comprised of a talented team of research specialists, doctoral students, and postdoctoral PhD and MD fellows, and collaborates closely with top scientist within the Division (Sluis-Cremer, Ambrose and Parikh Laboratories) and at other institutions.
To visit Dr. Mellors' biography page, please click here. Laboratory personnel descriptions are included below.
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John W. Mellors, MD Chief, Division Infectious Diseases Director, Virology Laboratories Director, HIV/AIDS Program UPMC Health System 3550 Terrace Street Suite S818 Scaife Hall Pittsburgh, PA 15261 Phone: 412-624-8512 Fax: 412-383-7982 Email: jwm1@pitt.edu Assistant: Lois Mathews Asst phone: 412-383-7963 Asst Email: lmm112@pitt.edu |
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Annie Bedison Mellors Lab S813 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-7205 Fax: 412-648-9153 Email: bedisona@dom.pitt.edu |
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Jessica Brehm Mellors Lab S814 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-8647 Fax: 412-648-9153 Email: jhb9@pitt.edu |
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Samantha Conroy Mellors Lab S814 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-8647 Fax: 412-648-9153 |
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Diana Koontz Mellors Lab S816 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-8409 Fax: 412-648-9153 Email: zonarich@pitt.edu |
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Beth Leslie Research Specialist IV S814 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-8647 Fax: 412-648-9153 Email: ell38@pitt.edu |
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Elias Halvas, PhD Research Assistant Professor of Medicine Mellors Lab S813 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8152 Fax: 412-648-9153 Email: ekh2@pitt.edu |
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Francis Hong, MD Mellors Lab S813 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8152 Fax: 412-648-8455 Email: feh10@pitt.edu |
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John McKinnon, MD, Ms Assistant Professor of Medicine Mellors Lab S827 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9012 Fax: 412-648-9153 Email: jem44@pitt.edu |
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Jeff Meteer Mellors Lab S814 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-8647 Fax: 412-648-9153 Email: jdm69@pitt.edu |
The University of Pittsburgh Mycology Research Unit (MRU) is devoted to research, patient care, and the training of physicians, other health care providers and researchers. The MRU is headed by M. Hong Nguyen, M.D., Director of Transplant Infectious Diseases and the Antimicrobial Management Program at UPMC, and Neil Clancy, M.D., Scientific Research Director. Our research mission is to understand mechanisms of pathogenesis and host defense against fungi and other opportunistic pathogens to devise novel diagnostic, preventive and treatment strategies. Our clinical missions are to provide state-of-the-art care for solid organ and stem cell transplant recipients, manage antimicrobial use through our institutional stewardship program, and conduct clinical and translational research on infectious diseases occurring among immunocompromised hosts. Our training mission is to educate and mentor the next generation of health care providers and researchers to assume leadership positions in clinical care and academics. In fact, these missions are overlapping and interactive, as we seek in each of our endeavors to unite the bench and the bedside. On-going lines of investigation in the MRU include: 1) basic research on the molecular pathogenesis of diseases caused by the fungi Candida albicans and Aspergillus fumigatus; 2) translational research investigating fungal antigens as targets for diagnostic test and vaccine development; 3) studies of antifungal susceptibility and resistance; and 4) clinical research on fungal diagnostics and outcomes and susceptibility to infectious diseases among transplant recipients. In addition to Drs. Nguyen and Clancy, our team includes physicians and pharmacists working on the Transplant ID and Antimicrobial Management services, Infectious Diseases fellows-in-training, research professors, post-doctoral research fellows and research technicians. In both research and patient care, we have extensive collaborations with scientists and clinicians throughout the United States and internationally.
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Minh-Hong Nguyen, MD Professor of Medicine Director, Transplant ID Program and Director Antibiotic Management Program S871 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-5193 Fax: 412-648-8455 Email: nguyenh@dom.pitt.edu |
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Cornelius “Neil” Clancy, MD Associate Professor of Medicine Director, Mycology Research Unit S867 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-0309 Fax: 412-648-8455 Email: clancyn@dom.pitt.edu |
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Hassan Badrane, PhD Research Assistant Professor of Medicine Nguyen/Clancy Labs S875 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8438 Fax: 412-648-8455 Email: badraneh@dom.pitt.edu |
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Shaoji Cheng, MD Research Associate Professor of Medicine Nguyen/Clancy Labs S869 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-0309 Fax: 412-648-8455 |
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Chen Du, PhD Nguyen/Clancy Labs S873 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-9928 Fax: 412-648-8455 Email: duc@dom.pitt.edu |
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Binghua Hao, MD Nguyen/Clancy Labs S879 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-0269 Fax: 412-648-8455 Email: haob@dom.pitt.edu |
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Me-Linh Luong, MD Visiting Research Scholar Nguyen/Clancy Lab S875 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-0269 Fax: 412-648-8455 Email: melinhl+@pitt.edu |
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Rima Abdel Massih, MD S831B Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-383-6567 Fax: 412-648-8521 Email: abdelmassihr@upmc.edu |
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Suresh Raman, PhD Nguyen/Clancy Labs S875 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8438 Fax: 412-648-8455 Email: ramans@dom.pitt.edu |
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Ryan Shields, Pharm D Falk Medical Building, Suite 3-A 3601 Fifth Avenue Pittsburgh, PA 15213 Phone: 412-246-6271 Fax: 412-648-6399 Email: shieldsrk@upmc.edu |
Urvi M. Parikh, Ph.D., is an Assistant Professor of Medicine in the Division of Infectious Diseases and Associate Director of the Microbicide Trials Network (MTN) Virology Core. Her work in the HIV field began in 1998 at Roche Diagnostics, in technical support and manufacturing of Amplicor Monitor HIV, HCV and CT/NG viral load kits. Her graduate work with Dr. John Mellors focused on elucidating mechanisms of drug resistance to nucleoside reverse transcriptase inhibitors, particularly the tenofovir-resistance mutation K65R. She was an NIH fellow at the National Institute of Infectious Diseases in Tokyo studying non-B HIV subtypes, and a visiting scholar at the University of Oxford, UK, studying HIV-1 reverse transcriptase structure. At the US Centers for Disease Control and Prevention (CDC), Dr. Parikh formulated and evaluated combinations of antiretroviral agents for potential use as topical gels, and conducted toxicity and efficacy studies in a pigtail macaque model. She also worked at CDC’s Botswana field site, supporting the laboratory in its transition to a new HIV chemoprophylaxis trial. She recently joined the MTN in April 2008. Her research with the MTN will include validation of HIV-1 infection endpoints in women who seroconvert during microbicide trials, assessment of possible effects of microbicides on HIV-1 natural history, and evaluation of drug resistance in breakthrough infections in trial participants.
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Urvi Parikh, PhD Assistant Professor of Medicine Associate Director Microbicide Trials Network Core Virology Lab S817-A Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-628-3103 Fax: 412-648-8521 Email: parikhu@dom.pitt.edu |
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Krista Eskay Parikh Lab S804 Scaife 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-6214 Fax: 412-648-8521 Email: ka33@pitt.edu |
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Kelley Gordon Parikh Lab S816 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-624-8409 Fax: 412-648-9153 Email: gordonk@dom.pitt.edu |
Our research focuses on:
Nonnucleoside reverse transcriptase inhibitor (NNRTI) induced conformational changes in HIV-1 reverse transcriptase (RT). Recent studies have shown that NNRTI can modulate the inter-subunit interactions between the 66kDa and 51kDa polypeptides of RT. The molecular mechanisms by which this occurs, and the impact that this has on RT enzyme functioning is not known. In light of this, the specific aims of this project are to: (1) determine the mechanisms by which NNRTI modulate the inter-subunit interactions and intra-subunit conformational changes of HIV-1 RT; and (2) define the molecular interactions in the HIV-1 RT dimer interface and to evaluate the consequences of altering the intrinsic dimeric stability on enzymatic activity.
HIV-1 RT dimerization as an antiviral target. HIV-1 reverse transcriptase is a heterodimeric enzyme consisting of a 66-kDa subunit (p66) and a p66-derived 51-kDa subunit (p51). The DNA polymerase and ribonuclease H (RNase H) activities of the enzyme are entirely dependent on the heterodimeric structure of the enzyme, suggesting that inhibition of the subunit-subunit assembly of RT provides an alternative target for HIV-1 inhibition. The specific aims of this project are: (1) to develop, optimize and validate an HTS assay for RT dimerization; and (2) to screen chemical libraries to identify compounds that inhibit RT dimerization.
Molecular mechanisms of HIV-1 RT resistance to nucleoside reverse transcriptase inhibitors (NRTI): Although NRTI therapy is initially quite effective in reducing the viral load in HIV-1 infected individuals, the viral burden inevitably rebounds despite continued therapy, due to the appearance of drug-resistant strains of HIV. The primary objectives of this project are to understand the molecular (phenotypic) mechanisms by which drug-resistant HIV-1 RT provides resistance to NRTI such as 3'-azido-3'deoxythymidine (AZT) by utilizing appropriate in vitro biochemical models and molecular modeling.
To visit Dr. Sluis-Cremer's biography page, please click here. Laboratory personnel descriptions are included below.
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Nicolas Sluis-Cremer, PhD Assistant Professor of Medicine S8170 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8457 Fax: 412-648-8521 Email: cremern@dom.pitt.edu |
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Sanjeewa Dharmasena, PhD S810 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8396 Fax: 412-648-8521 Email: sanjeewa@pitt.edu |
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Genevieve Doyon Health Science Research Fellow Sluis-Cremer Lab S810 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8396 Fax: 412-648-8521 |
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Brian Herman Sluis-Cremer Lab S810 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8396 Fax: 412-648-8521 Email: bdh9@pitt.edu |
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Kelly Huber Sluis-Cremer Lab S810 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8396 Fax: 412-648-8521 Email: kdh27@pitt.edu |
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Jessica Radizio Sluis-Cremer Lab S810 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 Phone: 412-648-8396 Fax: 412-648-8521 Email: jar51@pitt.edu |