Research

The Division of Infectious Diseases’ research focuses on a broad range of HIV studies examining HIV pathogenesis, prevention, treatment, and cure. Our investigators have expertise in conducting basic, translational, clinical, and public health research through NIH-funded, investigator-initiated research studies and through large NIH network studies including the ACTG (Advancing Clinical Therapeutics Globally) for HIV and Other Infections, the HVTN (HIV Vaccines Trials Network), and the MWCCS (MACS/WIHS Combined Cohort Study). Our faculty holds leadership roles in the Rustbelt Center for AIDS Research (CFAR), which is a partnership between the University of Pittsburgh and Case Western Reserve University.

Currently hundreds of monoclonal antibodies (mAbs) based therapeutics are approved for clinical use in the United States, the European Union, and several other countries. The major clinical indications of mAbs include cancers, infectious diseases, and immune diseases. The Center for Antibody Therapeutics (CAT) is dedicated to developing and commercializing antibody-based therapeutics to address unmet medical needs in the indications of cancers, viral diseases, and bacterial infections. Specifically, CAT’s current research interests include: 1) Development and engineering of fully human antibody domains (single domain Ab), fragments (scFv) and full-length antibodies by using phage and yeast display methodologies; 2) Design and generation of antibody composite molecules as diagnostics and therapeutics including antibody-radionuclide conjugates (RACs), antibody drug conjugates (ADCs), and Chimeric Antigen Receptors (CARs); and, 3) Creation of innovative bispecific/biparatopic Abs (BsAbs) for dual targeting. One major type of bsAb is immune cell (NK and T) engagers for mobilizing killing against infected/transformed cells.

Antimicrobial resistance is associated with nearly 5 million deaths per year globally. The Center for Innovative Antimicrobial Therapy (CIAT) was established to develop long-term solutions to address this growing public health crisis. CIAT brings together Principal Investigators with shared interests and complementary expertise that generate successful individual and collaborative research programs. Our faculty are internationally recognized experts in mechanisms of antimicrobial resistance, functional genomics, clinical trials, molecular diagnostics, pre-clinical infection models, small molecule development and alternative therapies, including bacteriophages, antimicrobial peptides, and fecal microbiota transplantation. The existing research infrastructure enables immediate translation of new scientific discoveries directly to the patient bedside. A focal point of our investigations is to study bacterial and fungal isolates from hospitalized patients to better design new countermeasures . Vast biorepositories and clinical databases have been developed to link microbial genomes to antimicrobial susceptibility patterns, infection characteristics, and patient outcomes. Scientists within CIAT are funded by NIH and foundation grants, and through industry partnerships. Our faculty are recognized leaders clinically and academically who have established collaborations at the forefront of research in the field of antimicrobial resistance.

Our mission is to apply advanced microbial genomic, data mining, and machine learning tools to study the evolution and epidemiology of serious pathogens. We have demonstrated that the use of genomic epidemiology in healthcare settings can mitigate the transmission of pathogens. Our research includes using these tools to optimize pathogen transmission investigations, determining or confirming the emergence of novel strains, and interrupting the spread of outbreak organisms in healthcare and our community.

Infections lead to significant morbidity and mortality nationally and globally. To better combat infections, we need to understand how the host immune system counteracts and eradicates pathogens and repairs collateral damage that occurs during infection. Pathogens can take advantage of our immune system for survival by enhancing immunosuppression, and by releasing potent host mediators, resulting in cell damage and destruction. In the Infectious Diseases Division, we develop in vitro models with primary human and animal cells and in vivo murine models to discover novel pathways of host resilience. We take advantage of human-derived samples from hospitalized patients, leverage mammalian models of infection, and use genetic and transcriptomic tools to understand the host response to infection. Our goal is to fill in knowledge gaps and generate better approaches for treating infections.

Fungal diseases are responsible for >1.5 million deaths globally per year, primarily in those with compromised immune function. Aspergillus, Candida, and Cryptococcus are important opportunistic fungi responsible for high mortality. The Center for Healthcare Mycology and Fungal Genomics was founded with the mission to improve health through better prevention, diagnosis and treatment of human fungal infections and the promotion of safer healthcare environments. Research programs encompass laboratory development and validation of new diagnostics and basic science of antifungal resistance, pathogenesis of infections, fungal genomics; and, culture-based and molecular detection of fungi in air and on healthcare textiles and inanimate surfaces. Research at the Center is funded through the National Institutes of Health, the Centers for Disease Control and Prevention, a biotechnology company, and, industry and foundation relationships. Center faculty collaborate with clinical faculty to provide state-of-the-art care for patients at UPMC with a wide range of difficult-to-treat yeast and mould infections by managing antifungal drug and fungal diagnostic stewardship programs. Center investigators are active members of Infectious Diseases Society of America guideline taskforce and the Mycoses Study Group Education and Research Consortium. Center faculty are recognized global leaders, both clinically and academically, in the field of medical mycology and fungal genomics.