Acute Lung Injury and COVID-19
The Acute Lung Injury (ALI)/Adult Respiratory Distress Syndrome (ARDS) Research Program is focused on the investigation of fundamental mechanisms in lung injury and repair. The program utilizes advanced tools in molecular, biochemical, and clinical investigation. Extensive collaborative interactions exist with the Departments of Surgery, Anesthesiology, Pathology, and Environmental Health.
The ALI Center Clinical Program is focused on clinical investigation of fundamental mechanisms in humans with sepsis-induced ALI. Extensive collaborative interactions exist with the Departments of Critical Care Medicine, Surgery, Anesthesiology, Pathology, and Environmental Health. The mission of the ALI/ARDS Center is to synergize basic and translational discoveries for patients with severe acute lung injury. The investigative component of this program provides a registry for patients to participate in current new treatments and diagnostics for this disorder and to also be contacted in the future for emerging new management strategies. Clinical facilities include the UPMC medical ICUs and the ALI Center clinical program, which are suitable for the isolation, recovery, and processing of human bronchoalveolar lavage and blood specimens.
Asthma and Environmental Lung Disease
Directed by Dr. Sally Wenzel (Chair, Department of Environment Occupational Health in the School of Public Health), and Dr. Anuradha Ray (Scientific Director), the University of Pittsburgh Asthma Institute, at the University of Pittsburgh Medical Center (UPMC), was founded in 2009 as a joint venture between the Department of Medicine’s Division of Pulmonary, Allergy and Critical Care Medicine, Children’s Hospital of Pittsburgh, and the Pediatric Environmental Medicine Center. The Institute’s mission is to increase the scientific understanding of asthma/allergic diseases across all ages, to translate these findings into innovative approaches and to implement these approaches in the asthma community through an integrated Institute of scientists, clinicians, educators, patients, and the community, thereby improving the health of asthma patients. The Institute focuses on both clinical research (creating an asthma database and tracking outcomes of asthma patients), as well as translational research (encouraging translation of clinical observations to mechanistic studies or basic research to patient-relevant outcomes, through increased communication and access to clinical samples and data to include epidemiologic studies, local environmental impact studies as well as the psychosocial aspects of chronic disease). The Asthma Institute has seven faculty MDs (including several allergy specialists), seven faculty PhDs (including a clinical psychologist), a research recruiter, a regulatory coordinator, three clinical research nurses, two certified asthma educators, one certified pulmonary function technician, five research coordinators, an operations/business manager, an administrative assistant, and a dedicated data entry person.
COPD and Lung Cancer
The Emphysema COPD Research Center (ECRC), led by Dr. Frank Sciurba, is supported by multiple NIH contracts and grants, the Pennsylvania tobacco settlement fund, and quality industry collaborations. The ECRC employs 12 FTEs, including 6 clinical research coordinators, 2 pulmonary physiology technologists, and a database manager. The backbone of the ECRC is its research registry. Since the inception of the ECRC registry in 1999, over 2800 patients have consented to allow maintenance of clinical data, research questionnaires, physiologic and radiographic data, and to be contacted for participation in clinical trials. Of these patients, nearly 1500 have been determined to be active, recruitable subjects based on recent contacts. The ECRC has placed an emphasis on maintaining contact with these patients and ensuring that members of the “active” registry are motivated to continue participation in potential ECRC activities. Staff are trained in the collection of high-quality pulmonary function measures including more advanced pulmonary physiologic and exercise testing, blood draws and processing, St. George Respiratory Questionnaire (SGRQ), and other validated and nonvalidated symptom, demographic, and quality-of-life questionnaires. Over 2,000 human blood specimens are stored including plasma, serum, RNA, DNA, and buffy coat. Over 80 highly characterized human lung tissue specimens from patients with COPD have also been collected. The translational program further includes extensive expertise in animal models of COPD and emphysema and in vitro exposure cell culture labs for cigarette smoke and e-cigarette exposure among others.
Cystic Fibrosis and Transplant
The Cystic Fibrosis Research Center (CFRC) at the University of Pittsburgh supports a broad spectrum of interactive, timely and significant projects that are in line with our mission of developing improved clinical treatments for CF. The CFRC has had program support from the NIH and CFF for twenty years, and the Center has expanded recently in exciting new directions, with additional resources that support highly collaborative, interdisciplinary team projects. The research palette has expanded with growing strengths in infectious mechanisms and immune defense, thus, adding to our traditional strengths in ion transport and CFTR biology. The bulk of CF research at the University of Pittsburgh is conducted using primary human airway cell cultures established from CF and non-CF tissues that are made available by the more than 50 lung transplants that are performed annually at the University of Pittsburgh Medical Center. State-of-the-art biochemistry, molecular biology, cell biology, and electrophysiology are used to study CFTR and ENaC functions in epithelial membranes, how these pathways contribute to normal airway function, how they are trafficked between various compartments of the protein secretory and recycling pathways, and how therapeutic approaches can be derived from this understanding of channel function. The overall concept guiding many of these studies is that airway ion and water transport determine the properties of the airway surface liquid, which in turn affects the efficiency of mucociliary clearance mechanisms. Studies of the pharmacological manipulation of channel biogenesis (correction) or channel activity (potentiation) fall into this category.
(correction) or channel activity (potentiation) fall into this category.
The Lung Transplantation program at Pitt is one of the oldest and largest lung transplantation programs in the country. The program continues to expand lung transplantation activity on a yearly basis and consistently performs more than 50 procedures per year. The program has one of the largest international patient cohorts followed prospectively post lung transplantation. Dr. Joseph Pilewski directs this program with participation by Dr. Bruce Johnson. The Transplantation Immunology Program led by Dr. John McDyer, is dedicated to a greater understanding of the basic biology of transplantation of the lung allograft. This multidisciplinary program incorporates surgical, immunologic, and medical expertise in the care and research of patients with end-stage lung disease who undergo lung transplantation.
HIV and Infectious Lung Disease
The University of Pittsburgh HIV Lung Research Center (HLRC) includes over 40 faculty members in various departments and divisions including Pulmonary, Infectious Diseases, Immunology, Medical Microbiology, the Center for Vaccine Research, and the Graduate School of Public Health. Its purpose is to increase the scientific understanding of HIV-associated lung diseases including infectious and non-infectious complications and to develop novel therapeutic and preventive approaches to decreasing the burden of lung disease in this population. Dr. Morris is the director of the Center. The HLRC has established a local data and specimen bank from HIV-infected persons and controls. With over 800 HIV+ individuals in their studies, the HLRC is actively performing bronchoscopies and longitudinal pulmonary function testing in these individuals as well as banking biospecimens, obtaining chest CT scans, echocardiograms, and right heart catheterizations. Calibration and verification procedures for spirometers are performed according to manufacturer and European Respiratory Society (ERS)/American Thoracic Society (ATS) recommendations with biweekly healthy control subjects used as a system check for spirometry and DLCO. The Center has banked plasma and serum available for almost all participants. Some participants have sputum and peripheral blood mononuclear cells stored.
Interstitial Lung Disease
The Simmons Center was established in 2001 as a multidisciplinary center devoted to research and treatment of interstitial lung disease with a focus on IPF. Under the direction of Dr. Daniel J. Kass (Director) and Dr. Kevin F. Gibson (Clinical Director), the center is comprised of faculty with expertise related to the diagnosis and management of the various presentations of interstitial lung disease. These include specialists in pulmonary disease, rheumatology, radiology, and sleep, as well as many other renowned clinical experts. The research infrastructure at the center includes multiple research coordinators, a huge collection of well phenotyped lung and peripheral blood samples and a detailed patient database. Current research efforts include basic investigations focused on the mechanisms of lung fibrosis, injury and repair, genomics and proteomics of lung fibrosis and the role of the genetics in determining the fibrotic phenotype. As part of the special attention given at the program to facilitation of rapid translation from bench to bedside, scientists at the center are also active in translational research, studies of biomarkers of disease progression and development of new therapeutic drug targets. Scientists at the program are funded by NIH grants, as well as by industry, and enjoy a deep collaborative relationship with investigators across the world.
Lung Senescence and Aging
Aging is a major risk factor for chronic lung diseases. The incidence of lung diseases increases with age, and accumulating evidence strongly suggests aging as a crucial contributor for disease initiation and Progression. Pitt has built a strong focus on aging-related research with the Center for Aging and Population Health, the Pitt Pepper Center, and the Aging Institute. As part of the the Tristate SenNet Consortium, Dr. Melanie Königshoff investigates the heterogeneity of lung aging mechanisms in healthy and diseased lungs and develops novel models to translate these findings to humans. Dr. Jonathan Alder is an authority in telomere biology and age-related lung diseases. His laboratory, in collaboration with Dr. Toren Finkel, published a model driving senescence to understand the consequences of telomere dysfunction, a hallmark of aging. Dr. Oliver Eickelberg is a leading expert in pulmonary translational medicine. His research focuses on mapping efforts of the lung, including the lung aging atlas mapped by single cell transcriptomics and deep tissue proteomics, and he is a Core PI within the TriState SenNet. Dr. Bill Chen, who is faculty at the Aging Institute and Director of the Small Molecule Therapeutics Center, focuses on rapid, high-throughput screening systems to identify novel drugs for lung diseases. With Dr. Finkel, he is the co-founder of Generian, Inc., a start-up company that focuses on drug development for age-related diseases.
Microbiome and Infection
The University of Pittsburgh Center for Medicine and the Microbiome (CMM), co-directed by Dr. Alison Morris and Dr. Barbara Methé, is an interdisciplinary biomedical research facility providing technologic support for the study of microbial communities using genomics-based, high-throughput technologies, such as 16S (and other biomarkers), and metagenomic and metatranscriptomic sequencing of complex biologic and environmental samples. In addition, the Center provides bioinformatic, computational modeling and statistics support for the analysis of complex sequencing datasets including taxonomic and functional classifications, ecological measurements of diversity, distribution, and abundance, and routines for annotation and read mapping of metagenomic and metatranscriptomic to reference genomes using state-of-the-art, open-source pipelines. The Center also develops and maintains a variety of software modules to conduct statistical and comparative analyses. The center hosts microbiome working groups, invited speaker series and multidisciplinary retreats. There are currently over 100 members in a variety of fields including Medicine, Pediatrics, Surgery, Immunology, Microbiology and Molecular Genetics, and Pathology. In addition, CMM faculty have specific expertise in lung microbiome studies, having participated in the Lung HIV Microbiome Program and the Genomics Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis program. The intellectual and research resources of these groups create an ideal training environment.
Pulmonary Hypertension / Vascular Biology
PACCM shares research space with the Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute (VMI) at the University of Pittsburgh. The VMI harnesses interdisciplinary teams of researchers in hemostasis; red blood cell biophysics; transfusion medicine; cardiovascular biology; mitochondrial biology/energetics; cell survival and autophagy; and nitrite-nitric oxide and reactive oxygen species biochemistry to expand our understanding of the control of cell survival and energetics, blood flow to organ systems, and the development of novel therapies to enhance these properties and increase angiogenesis, blood flow, and cellular survival. PACCM and VMI collaborations are especially strong in the area of pulmonary hypertension research as part of the Center for Pulmonary Vascular Biology and Medicine at the University of Pittsburgh and UPMC. A multi-disciplinary clinical and research center for pulmonary hypertension with a focus on comprehensive and state-of-the-art care of patients, the Center also focus efforts on innovative ways to identify pulmonary hypertension early such that prevention of this disease may be a reality, to identify the elusive molecules that lie at the beginning origins of this disease, and to develop new treatments that could reverse or cure this disease.
The UPMC Sleep Medicine Center is a multidisciplinary program incorporating respiratory medicine, psychiatry, otolaryngology, and bariatric surgery specialists. Center research focuses on the pathophysiology of sleep-disordered breathing in patients with advanced cardiomyopathy, as well as clinical research in the medical therapy of obstructive sleep apnea and hypoventilation syndromes. The Center utilizes advanced tools in molecular, physiologic, and clinical investigation. Extensive additional collaborative interactions exist with the Heart and Vascular Institute, the Department of Otolaryngology, and the Graduate School of Public Health.
PACCM sleep researchers are also integral members of the Center for Sleep and Circadian Science (CSCS) Formally established in 2017, the mission of the CSCS is to advance the science and practice of sleep and circadian medicine through innovations in research, education, and clinical care. CSCS faculty, trainees, and staff are engaged in a wide range of research projects focused on sleep and circadian health, investigating the critical role that sleep and circadian rhythms play in physical, mental, and cognitive health across the lifespan. Center investigators and staff have also developed important tools widely used by researchers across the country and abroad.