Biospecimen Core

The The TriState SenNet Biospecimen Core (BC) will focus on two intercorrelated tissues of high relevance for human health to generate and refine a spatially- and age-resolved senescent tissue map: the lung and the heart. The investigators at the Ohio State University (OSU), the University of Pittsburgh (Pitt), and the University of Rochester Medical Center (URMC) will collect, process, classify, and distribute high-quality, clinically annotated, biological specimens from normal human lung and heart tissue (and corresponding primary cells, bronchoalveolar lavage, airways, vessels, and lymph nodes) to provide the fundamental basis for the construction of high-resolution, multi-modal, and multi-dimensional senescence maps. The Core follows ISBER and NCI Best Practices for Biorepositories, with standard operating procedures (SOPs) in place to ensure the highest biospecimen and clinical information quality to meet all legal and ethical standards including broad donor consent. The biorepository efforts are approved through OSU, Pitt, and URMC IRB protocols that cover the procurement, processing, and distribution of human biospecimens.

Graphic representation of the localization of the tissue samples collected from human lung and heart. Collected samples will be processed immediately after organ procurement and divided into fixed and fresh tissue according to the type of sample required by Biological Analysis Core.

The TriState SenNet BC will 1) maintain and grow a state-of-the-art biorepository of lung and heart tissue procured from healthy individuals with appropriate diversity and across the lifespan and 2) establish and define a seamlessly integrated two-phased workflow of tissue processing and distribution, which is based on a) initial processing and histo-/pathological tissue evaluation and b) secondary distribution of whole tissue, precision cut tissue slices (PCTS), and purified cell populations, all derived from the same originating tissues, for subsequent high-content tissue analysis.

Leadership

Contact PI: Mauricio Rojas, MD

Professor of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine
Associate Vice-Chair of Research, Department of Internal Medicine
Ohio State University

Dr. Rojas is the Associate Vice-Chair of Research and the Scientific Director of the Surgical Biorepository of the Department of Internal Medicine at Ohio State University. Previously, he was the scientific director of the Dorothy P. & Richard P. Simmons Center for ILD at the University of Pittsburgh. Dr. Rojas’s research interest is in the determination of age-related mechanisms that contribute to increased susceptibility to lung fibrosis, with an emphasis on the exhaustion of mesenchymal stem cells and mechanisms of persistence of senescence in lung fibroblasts. He is a pioneer in the development of pre-clinical and ex-vivo models of lung injury and fibrosis including endotoxin-, bleomycin-induced murine models of lung injury and fibrosis, mouse and human precision-cut lung slices (PCLS), and assays to determine senolytic activity of compounds in primary human senescence cells. Dr. Rojas has developed a Human Lung Tissue Biorepository from tissue samples from heart, lung, spleen, fat tissue, skin, and muscle from healthy donors and lung disease patients. The biorepository includes the continuous collection of fresh and frozen tissue samples for molecular, biochemical, cellular and pathological analysis, single cell suspensions for sc-RNAseq and FACS analysis, and isolated primary lung fibroblasts and lung epithelial cell lines. Dr. Rojas is the contact PI of a U01 consortium grant program focused on the development of molecular maps of lung aging and a member of the Human Lung Cell Atlas. Dr. Rojas has published extensively in the field of senescence of stem cells, lung fibroblasts, and lung fibrosis. Dr. Rojas serves as ad hoc reviewer of multiple NIH study sections, and he has been speaker for several NHLBI and NIA workshops including the “DNA damage, Telomeres, and Senescence in Lung Aging and Disease” and “Immunity Aging and COVID19.” Dr. Rojas is a member of the NHLBI Program Project review committee, and he is the founder of the Lung Aging Group at the RCMB assembly of the American Thoracic Society. Additionally, Dr. Rojas has organized 3 international conferences focused on lung aging: one in the US (Pittsburgh-Munich Lung Conference 2014) and two in Europe (Transatlantic Conference and Comprehensive Pneumology Center Deutsches Zentrum Conference).

Co-Lead PI: Oliver Eickelberg, MD

Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Vice-Chair for Basic and Translational Medicine, Department of Medicine
University of Pittsburgh

Dr. Eickelberg is a leading expert in pulmonary translational medicine. Dr. Eickelberg’s research has unraveled novel mediators and cell types involved in lung fibrosis. He has previously established several biospecimen cores, including an entire Pulmonary Tissue Bank and a longitudinal Lung Transplant Repository. Dr. Eickelberg is PI on the Human Lung Cell Atlas Initiative and is involved in several mapping efforts of the lung, including the lung aging atlas mapped by single cell transcriptomics and deep tissue proteomics, the integrative map of cell state changes in lung fibrosis, the SARS-CoV-2 entry gene map across multiple tissues, and the matrisome map of the lung. He is an elected member to the American Society of Clinical Investigation and has significant experience in coordinating large scale consortia and mapping initiatives, which will further contribute to the success of this TriState SenNet TMC.

Co-Lead PI: Alison Morris, MD, MS

Professor of Medicine, Immunology, and Clinical and Translational Research
Division Chief, Pulmonary, Allergy and Critical Care Medicine
Director, Center for Medicine and the Microbiome
Vice Chair for Clinical Research, Department of Medicine
UPMC Chair in Translational Pulmonary and Critical Care Medicine

Dr. Morris has a long track record of NIH funding and in participating in and leading multi-center studies including the Lung HIV Study, the Lung HIV Microbiome Project, and the Genomic Research in Alpha-1 antitrypsin and Sarcoidosis (GRADS) study. Key scientific discoveries include the role of colonizing infections in lung dysfunction and establishing the existence of the lung microbiome and its role in lung disease. In addition, she established the University of Pittsburgh HIV Lung Research Center as well as the Center for Microbiome and Medicine. An elected member of the American Society of Clinical Investigation and American Association of Physicians, Dr. Morris’s expertise in leading large cohort epidemiologic studies, microbiome analyses of lung and other diseases, and work with biospecimen repositories will significantly contribute to the success of mapping senescence across the lifespan in the TriState SenNet TMC.

Co-Lead PI: Irfan Rahman, PhD

Professor of Environmental Medicine, Medicine (Pulmonary) and Public Health Sciences
Director of Center for Flavoring Inhalation Toxicology
University of Rochester Medical Center

Dr. Rahman’s research interests include oxidative stress, inflammation, molecular clock, mitochondrial dysfunction, epigenetics, and cellular senescence by environmental tobacco smoke/tobacco products (cigarette smoke, e-cigarettes, waterpipe/hookah, and cigars) in lung (Chronic Obstructive Pulmonary Disease and idiopathic pulmonary fibrosis), as well as oral/periodontal diseases. His research is funded by the NIH, and he is the PD/site PI for the TCORS U54. He has published over 300 articles in peer-reviewed journals, and has been invited to contribute to numerous textbooks and journals (citations > 46,500, h-index = 106, i-index = 258; Highly Cited Researchers, 2014, 2015, and 2016 by Thomson Reuters). He has been ranked #16 (out of 52,718 active Respiratory & Allergy Researchers) by Ioannidis et al 2020 and is the editor/author of Inflammation, Aging, Diet and Nutrition (Elsevier 2013). Dr. Rahman has served as a member on several NIH study sections (SIEE, chartered member), as a chartered member of USA Veterans Administration panel on Pulmonary study section, and as chair of the California Cardiopulmonary tobacco research program. Additionally, he is an Associate Editor on numerous journals (Nature Scientific Reports, International Journal of COPD, Journal of Inflammation, and Experimental Lung Research), a past Associate Editor of the European Respiratory Journal, and is currently a member of the editorial boards of several international journals (Am. J. of Respiratory Cell & Molecular Biology, Therapeutic Advances in Respiratory Disease, Current Respiratory Medicine Reviews, Respiratory Research , Antioxidants Redox Signaling, and Frontiers in Respiratory Pharmacology). He is a member of American Thoracic Society (ATS), American Physiological Society, and Society of Toxicology (SOT), and past-President for Inhalation Respiratory Specialty Section of the SOT, and Chair of Lung Aging Interest Group of the ATS. Dr. Rahman has won numerous awards including the outstanding Senior Investigator Award by the Oxygen Society of California (2006), Senior Toxicologist Award by the SOT (2017), and International Chemical Society (2019). He will bring his expertise in mapping of adult lungs, mouse models of cellular senescence, and cellular aspects to the TriState SenNet TMC.

Co-Investigators

Stephen Chan, MD, PhD

Professor of Medicine, Division of Cardiology
Director, Vascular Medicine Institute
Associate Chief of Cardiology, Basic Science
University of Pittsburgh

Dr. Chan is an elected member to the American Society of Clinical Investigation and has devoted his career to leading a basic and translational research program and building of biorepositories and clinical centers to study pulmonary and cardiovascular disease. His expertise in cardiopulmonary science and biobank resources are critical to build a Lung and Heart Senescence Atlas.

Jeffrey Horowitz, MD

Professor of Internal Medicine, Division of Pulmonary, Critical Care & Sleep Medicine
Director, Division of Pulmonary, Critical Care & Sleep Medicine
Ohio State University

Dr. Horowitz is an expert on cellular and molecular aspects of chronic fibrotic lung diseases such as Idiopathic Pulmonary Fibrosis. He has contributed to the knowledge of regulatory mechanisms of fibroblast survival and function and extracellular matrix derived signaling. He is member of the editorial board of the American Journal of Respiratory Cell and Molecular Biology, the American Journal of Pathology, and Respirology. He is an NIH-funded investigator and recipient of several awards including Fellowship of the American College of Chest Physicians, the T. Franklin Williams Scholar of the Association of Specialty Professors, and the Dalsemer Award for Research in Interstitial Lung Disease from the American Lung Association.

Gloria Pryhuber, MD

Professor of Pediatrics, Division of Neonatology
Professor of Environmental Medicine
University of Rochester

Dr. Pryhuber trained at the Cincinnati Children’s Hospital Medical Center as Fellow in Neonatal-Perinatal Medicine, Proctor Research Scholar, and member of the Pulmonary Biology Program. In the last 10 years, in addition to practicing as a Neonatologist, she has served as PI for the multicenter NHLBI Prematurity and Respiratory Outcomes Program (PROP); as Lead Site Investigator for the NIAID UR-Respiratory Pathogens Research Center (RPRC) “Prematurity Respiratory Outcomes, Immune System and Microbiomes (PRISM)” Study; and as Site Investigator for the NIH multicenter Environmental Influences on Child Health Outcomes (ECHO) Program. Dr. Pryhuber has also served as PI for both Phase I and Phase II of the NHLBI Lung Development Molecular Atlas Program (LungMAP, LungMAP.net) Human Tissue Core (HTC) and for the NIH Human Biomolecular Atlas Program (HuBMAP), working with the national organ transplant network and creating the BioRepository for INvestigation of Diseases of the Lung (BRINDL) that provides multiple research centers with unique opportunities to investigate the developing, adult, and COVID-19 affected human respiratory tract and immune system in an unusually holistic manner. She has extensively applied and enabled multi-omic study of human molecular biology and serves as Chair of the HuBMAP Policy Working Group. Dr. Pryhuber actively fosters the growth and collaborations of intramural and extramural investigators and clinicians in neonatology, pulmonology, infectious disease, obstetrics/perinatology, immunology, microbiology, pathology, molecular biology and genomics, and with many investigators concerned with diseases of perinatal development and aging. Dr. Pryhuber has established repositories of late gestation and early childhood developing lung samples via the Lung MAP at the University of Rochester (URMC), which resulted in the creation of the Biorepository for Investigation of Neonatal Diseases of the Lung (BRINDL), composed currently of >330 donors (approximately 50% male) ranging in age from 24 weeks premature to 80 years of age.

Konstantin Shilo, MD

Associate Professor of Pathology
Director, Division of Thoracic Pathology
Ohio State University

Dr. Shilo has extensive expertise as a thoracic pathologist, especially in the evaluation of lung toxicity and pathologies in both human samples and animal models of lung diseases. His research efforts include tumor biology, tumor protein expression profiling, and lung toxicity in the setting of solid organ transplantation, as well as in evaluation of lung toxicity in genetically modified viral infection and mechanisms of acute lung injury.

Humberto Trejo Bittar, MD

Assistant Professor of Pathology
University of Pittsburgh

Dr. Trejo Bittar is an experienced pathologist, specialized in thoracic pathology. He has worked closely with the UPMC Biobank to assess human tissue biospecimen performing microscopic diagnosis and examination of tissue. Dr. Bittar is a founding member of the Rapid Autopsy Program at UPMC allowing access to well-preserved, post-mortem tissue from any organ with or without pathology, which is a critical asset for the TriState SenNet TMC.