Administrative Core
The TriState SenNet Administrative Core (AC) will provide the essential infrastructure to enable synergy and coordination of the individual cores and communication with other TMCs, the larger SenNet Network, and the NIH. The aims of the Administrative Core are necessarily broad and focus on leadership and internal management plans. They include providing a leadership and management plan for the TriState SenNet TMC; the coordination and facilitation of interactions of the TriState SenNet TMCs cores and projects; and the building of a broad network for interactions with other SenNet sites and the NIH program. The overarching goal of the AC is to maximize synergy amongst the core teams at all four institutions and to create an innovative and stimulating environment that ensures and fosters rigorous science. The AC thus supports and ensures the overall goal of the TriState SenNet TMC to identify, map, and functionally characterize the heterogeneity of senescent cells at single-cell resolution in multiple tissues across the human lifespan.
The Interactive Universe of the TriState SenNet TMC
Leadership
PD/PI: Toren Finkel, MD, PhD
Distinguished Professor of Medicine, Division of Cardiology
G. Nicholas Beckwith III and Dorothy B. Beckwith Chair in Translational Medicine
Director, Aging Institute of UPMC and Pitt
University of Pittsburgh
Over the last three decades, the Finkel laboratory has made fundamental contributions to our understanding of the role of reactive oxygen species and mitochondrial function in senescence, aging, and age-related diseases (>200 peer-reviewed articles, citations >79,000, h-index = 109). Recently, he has also co-developed several small molecules in Phase I human trials. Dr. Finkel is the Director of the Aging Institute of the University of Pittsburgh/UPMC. He currently serves as a Co-PI of a U01 to Map Age-Related Changes in the Lung and was the previous US Coordinator for a multi-PI Leducq Transatlantic Consortium that sought to identify and map cardiac stem cells.
Co-PD: Melanie Koenigshoff, MD, PhD
Visiting Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Associate Chief of Research, Division of Pulmonary, Allergy and Critical Care Medicine
University of Pittsburgh
Dr. Koenigshoff is a physician-scientist with a strong focus on lung aging mechanisms and how these contribute to chronic lung disease, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. (>100 peer-reviewed articles in leading journals, citations > 6,000, h-index = 42, i10-index = 89). Her translational research program focuses on the comprehensive characterization of biospecimen from human tissue and patient cohorts, including broad phenotyping and mechanistic studies of lung cells using state of the art molecular and computational biology tools. Her laboratory further pioneered the development and applications of clinically relevant patient-derived 3D human tissue-based models, such as precision-cut tissue slices and organoids that allow the identification and validation of potential triggers of senescence and testing of novel drugs in an individualized fashion. Dr. Koenigshoff has significant experience in coordinating large-scale consortia and is a member of the American Thoracic Society Interesting Group of Lung Aging, which will further contribute to the success of this TriState SenNet TMC.
Co-PD: Ana L. Mora, MD
Professor of Internal Medicine, Division of Pulmonary, Critical Care & Sleep Medicine
Associate Director for Pulmonary Research, Davis Heart & Lung Research Institute (DHLRI)
Ohio State University School of Medicine
Dr. Ana L. Mora is Professor of Internal Medicine in the Division of Pulmonary, Critical Care & Sleep Medicine at the Ohio State University (OSU) and the Director for Pulmonary Research at the Davis Heart & Lung Research Institute (DHLRI). She has pioneered aging studies in the lungs and investigates aging as a risk factor for lung fibrosis. She has also contributed to a greater understanding of aging-related ER stress and mitochondrial dysfunction in age-related lung diseases. Dr. Mora has served on numerous study sections including the LIRR, for which she currently serves as a permanent reviewer. She has participated as an expert in several NIH workshops and has received several NIH grants, including K01, R01, U01, and U54 awards. She is currently a member of the editorial board for the AJP Lung Cellular and Molecular Physiology Journal and the American Journal of Respiratory Cell and Molecular Biology. The current director of the DHLRI at OSU, Dr. Mora also has extensive previous leadership and administrative expertise, having served previously as the Director of Education at the Aging Institute and the Director of the Hemodynamic Core of the Vascular Medicine Institute at the University of the Pittsburgh.
Co-PD: 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.
External Advisory Board
GR Scott Budinger, MD
Division Chief, Pulmonary and Critical Care
Ernest S. Bazley Professor of Airway Diseases
Northwestern University
Dr. Budinger laboratory is interested in understanding how aging biology intersects with the age-related risk of acute and chronic lung disease. His laboratory has focused on the proteostasis network, a system of proteins that is responsible for maintaining all of the proteins in the cell in their native functional state. In model organisms, there is a programmed signal that induces a progressive decline in function of the proteostasis network, and interruption of this pathway extends lifespan and improves resilience in the face of environmental stress.
The Budinger lab is testing whether a similar decline in the function of the proteostasis network happens in the lung, and whether this loss of “proteostasis reserve” underlies the increased susceptibility to pneumonia, and the increased risk of lung fibrosis and emphysema observed in older individuals. The long-term goal of this work is to develop treatments that can reduce these age-related risks and preserve lung health over the lifespan.
Ana Maria Cuervo, MD, PhD
Professor of Developmental and Molecular Biology
Professor of Anatomy and Structural BIology
Professor of Medicine (Hepatology)
Albert Einstein College of Medicine
Dr. Cuervo is considered a leader in the field of protein degradation in relation to biology of aging and has been invited to present her work in numerous national and international institutions, including name lectures as the Robert R. Konh Memorial Lecture, the NIH Director’s, the Roy Walford, the Feodor Lynen, the Margaret Pittman, the IUBMB Award, the David H. Murdoxk, the Gerry Aurbach, the SEBBM L’Oreal-UNESCO for Women in Science, the C. Ronald Kahn Distinguished Lecture and the Harvey Society Lecture. She has organized and chaired international conferences on protein degradation and on aging, belongs to the editorial board of scientific journals in this topic, and is currently co-editor-in-chief of Aging Cell.
Dr. Cuervo has served in NIH advisory panels, special emphasis panels, and study sections, the NIA Scientific Council and the NIH Council of Councils and has been recently elected member of the NIA Board of Scientific Counselors and member of the of the Advisory Committee to the NIH Deputy Director.. She has received numerous awards for the pioneerign work of her team such as the 2005 P. Benson Award in Cell Biology, the 2005/8 Keith Porter Fellow in Cell Biology, the 2006 Nathan Shock Memorial Lecture Award, the 2008 Vincent Cristofalo Rising Start in Aging Award, the 2010 Bennett J. Cohen Award in Aging Biology, the 2012 Marshall S. Horwitz, MD Faculty Prize for Research Excellence and the 2015 Saul Korey Prize in Translational Medicine Science. She has also received twice the LaDonne Schulman Teaching Award. In 2015 she was elected International Academic of the Royal Academy of Medicine of the Valencia Community and in 2017, she was elected member of the Real Academia de Ciencias Exactas, Fisicas y Naturales. She was elected member of the American Academy of Arts and Sciences in 2018 and member of the National Academy of Science in 2019.
Mark T. Gladwin, MD
Vice President for Medical Affairs, University of Maryland, Baltimore
John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine
Mark T. Gladwin, MD was appointed as the Dean of the University of Maryland School of Medicine (UMSOM) and Vice President for Medical Affairs at the University of Maryland, Baltimore in August 2022. He is a leading heart, vascular, and lung physician-scientist. He maintains an active research group and is currently PI of two R01 awards, a P01 award, and a clinical trials U award. He has published > 450 manuscripts (google scholar h-index of > 120). His scientific discoveries include the finding that the nitrite salt is a biological signaling molecule that regulates physiological and pathological hypoxic responses, blood pressure and flow, and dynamic mitochondrial electron transport. He also characterized the role of hemoglobin and myoglobin as signaling nitrite reductases that regulate NO production under hypoxia, and his 2003 publication on this work has been cited > 1,800 times and is in Nature Medicine’s Classic Collection. His work on the nitrite anion has led to the development and licensing of intravenous, oral and inhaled nitrite as a human therapeutic, with completion of animal toxicology, GMP formulations and phase Ia and Ib clinical trials, with licensing of the drug. Phase II trials of inhaled nitrite are now underway for the treatment of pulmonary arterial hypertension, metabolic syndrome, and heart failure with preserved ejection fraction. In addition to studies of nitrite, he characterized a novel mechanism of disease, hemolysis-associated endothelial dysfunction. This work has described a state of resistance to NO in patients with sickle cell disease, malaria, transfusion of aged blood, and other hemolytic conditions, caused by scavenging of nitric oxide by hemoglobin that is released into plasma during hemolysis. These studies translated to clinical, and epidemiological description of a human disease syndrome, hemolysis-associated pulmonary hypertension. Dr. Gladwin has served as PI on several multicenter phase II-III clinical trials in SCD patients, including the DeNOVO trial of NO therapy for acute pain crisis in patients with sickle cell disease, the Walk-PHASST trial of sildenafil for PH secondary to sickle cell disease, the EPIC trial of poloxomer 188 for vaso-occlusive painful crisis, the STERIO-SCD trial of the sGC stimulator riociguat, and the currently running SCD-CARRE, a clinical trial of exchange transfusion therapy.
Naftali Kaminski, MD
Division Chief, Pulmonary, Critical Care and Sleep Medicine
Yale School of Medicine
Dr. Kaminski’s main research interests involve applying genomic approaches to elucidate basic mechanisms and improve diagnosis and treatment of Idiopathic Pulmonary Fibrosis (IPF), a chronic mostly lethal and currently untreatable scarring lung disease and other chronic lung diseases such Chronic Obstructive Pulmonary Disease (COPD), severe asthma and sarcoidosis. His group pioneered the application of high throughput genome scale transcript profiling in advanced lung disease. Among his key scientific achievements are: the discovery of novel molecules with significant active roles in pulmonary fibrosis, including matrix metalloproteases (MMP7, MMP19) and phosphatases (SHP2, MKP5), demonstrating that microRNAs, a family of small non-coding RNAs, are differentially expressed in IPF, and that some of them (let-7, mir-29, mir-33) are mechanistically involved in lung fibrosis, and the discovery that the outcome of patients with IPF can be predicted based on the expression of peripheral blood proteins and genes, a finding with practical implication because of the need for risk stratification and transplant prioritization.
Since completing his clinical training, Dr. Kaminski has authored more than 275 research papers, review articles and book chapters and has given numerous invited talks at national and International conferences. Since he finished his fellowship in 2000, Dr. Kaminski has been consistently funded by NIH and is the PI of multiple NIH grants. Dr. Kaminski was a recipient of the Marvin I. Schwarz Award for contributions to patient care and research in pulmonary fibrosis from the Coalition for Pulmonary Fibrosis in 2010 and the University of Pittsburgh Innovator Award in 2012. In 2013, Dr. Kaminski received the American Thoracic Society Recognition of Scientific Achievements award, as well the Helmholtz Institute International Fellow. In 2015 he was elected to the Association of American Physicians. In 2016 he was elected as Fellow of the European Respiratory Society (ERS) , and won the the European Respiratory Society Gold medal for Interstitial Lung Disease. In 2018, Dr. Kaminski received the Andy Tager Excellence in Mentorship Award from the Respiratory Cell and Molecular Biology Assembly of the American Thoracic Society and was elected fellow of the American Thoracic Society. Dr. Kaminski is active on the ATS and was the editor of “Gene Express”, a column on genomics in the initial days of the ATS Website, a member and chair of the Program Committee of the Assembly on Respiratory Cell and Molecular Biology of the ATS, and member of the ATS Research Advocacy Committee, and Chair of the Assembly on Respiratory, Cell, and Molecular Biology at the American Thoracic Society. He was an associate editor of the American Journal of Respiratory and Critical care Medicine, a member of multiple editorial boards and recently the Deputy Editor of Thorax, BMJ. Dr. Kaminski served as the President of the Association of Pulmonary, Critical Care and Sleep Division Directors in 2019.
Christina Leslie, PhD
Memorial Sloan Kettering Cancer Center
Dr. Leslie is well-known for developing machine learning approaches—algorithms for learning predictive models from data—for the analysis and interpretation of high-throughput biological data, especially from next-generation sequencing. Her research group uses machine learning and other computational methods to study transcriptional and post-transcriptional gene regulatory mechanisms, epigenetic programs governing cell fate decisions in differentiation, and the dysregulation of gene expression programs in cancer. A strong focus area is the analysis of differentiation programs in the immune system and dysfunctional immune cell states in cancer.
Dr. Leslie is Co-Principal Investigator of an NCI U54 Center for Cancer Systems Immunology at MSKCC, which studies the role of tumor-immune interactions in cancer and response to cancer immunotherapy. She is also co-chair of the Analysis Working Group of the ENCODE 4.0 project, where she leads a computational project to incorporate data on 3D genomic architecture into epigenomic and gene regulatory models.
Internal Advisory Board
Anne B. Newman, MD, MPH
Katherine M. Detre Endowed Chair, Population Health Sciences
Director, Center for Aging and Population Health
Professor of Medicine and Clinical & Translational Science
Clinical Director, Aging Institute of UPMC and Pitt
University of Pittsburgh Graduate School of Publica Health
Dr. Newman’s research focuses on aging, including the determinants of physical and cognitive function as well as successful aging and longevity. She has special expertise in the study of cardiovascular disease and aging and body composition, sarcopenia, and physical functioning. She is presently the Principal Investigator (PI) of several long term cohort studies and clinical trials in older adults funded by the National Institute on Aging (NIA).
Dr. Newman is professor and chair of the Department of Epidemiology in the Graduate School of Public Health at the University of Pittsburgh with a secondary appointment in the Department of Medicine and with the Clinical and Translational Science Institute (CTSI) at the University of Pittsburgh. She was appointed to the Katherine M. Detre Endowed Chair of Population Health Science in the Graduate School of Public Health in June, 2014. Dr. Newman is an elected member of the American Epidemiology Society (AES), the American Association of Physicians (AAP) and the Delta Omega Honor Society in Public Health. Dr. Newman is certified by the American Board of Internal Medicine with added qualifications in geriatric medicine. She directs the Center for Aging and Population Health in the Graduate School of Public Health which includes an NIA National Service Award for training epidemiology doctoral fellows in the Epidemiology of Aging. She also serves as Co-Director for the NIA funded Older Americans Independence Center in the Department of Medicine.
Harinder Singh, PhD
Director, Center for Systems Immunology
Dr. Singh’s interests are focused on the analysis of transcription factors and gene regulatory networks (GRNs) that orchestrate the development and functioning of innate as well as adaptive cells of the immune system. As an HHMI Investigator at the University of Chicago, his lab discovered that the Ets family member PU.1 was required for the development of multiple innate and adaptive immune cell lineages. The Singh lab has systematically illuminated the molecular functions of PU.1 in the development of B cells and macrophages. In a collaboration, he cloned IRF4, a PU.1 partner. IRF4 regulates plasma cell differentiation and its molecular actions are antagonized by the related protein IRF8 to promote the germinal center B cell fate. IRF4 and IRF8 are immune-system specific members of the IRF family of transcriptions factors that have crucial and diverse functions in regulating B and T lymphocytes as well as macrophages and dendritic cells. He has elucidated key activities of IRF4 in the genomic programming of Th17 cells as well as dendritic cells. A notable structural finding has been the discovery of distinct types of composite regulatory elements in immune response genes that are cooperatively bound by IRF4 or IRF8 with the Ets family member PU.1 or the AP-1 member BATF. Using structural and functional genomics as well as computational modeling, the Singh lab is analyzing coherent networks of transcription factors and the large sets of genomic regulatory sequences through which they act. This is enabling us to assemble GRNs underlying B and macrophage cell fate specification, pre-B and plasma cell differentiation, and the programming of dendritic as well as CD4 T cell responses. He is interested in utilizing the knowledge of GRNs to engineer immune cells with new effector or regulatory capabilities that can be therapeutically harnessed.
Lang Li, PhD
The Ohio State University College of Medicine
As a member of the Cancer Biology Program at the OSUCCC – James, Dr. Li’s research focuses on two cancer-related areas: 1) electronic medical record data sources and medical informatics approaches to investigate risk factors (e.g., genomics and drug interactions) that predict either drug efficacy or adverse drug events and 2) the use of public domain cancer genomics and transcriptomics data, as well as system biology and system pharmacology approaches, to investigate cancer drug resistance and cancer metastasis mechanisms. In particular, Dr. Li’s lab focuses on target identification and drug response prediction.
Although his informatics methodology research is not necessarily cancer specific, his current research investigates cancers of the breast, colon, liver and lung. Dr. Li has authored or co-authored several publications in peer-reviewed journals, including BMC Medical Genomics, Clinical Pharmacology & Therapeutics, and International Journal of Molecular Sciences.
Richard K. Wilson, PhD
Professor of Pediatrics
The Ohio State University College of Medicine
Dr. Wilson is the founding executive director of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital (NCH). He also holds the Nationwide Foundation Endowed Chair in Genomic Medicine and is a professor in the Department of Pediatrics at The Ohio State University College of Medicine. As a member of the Cancer Biology Program at the OSUCCC – James, Dr. Wilson is interested in utilizing the tools and technologies of modern genomics, and developing new derivatives thereof, to ask and answer questions of cancer biology that have eluded previous researchers, including understanding the role of genome sequence and structure, gene expression and epigenomics in the initiation and progression of cancer. He is also interested in utilizing research discoveries along with these same tools and technologies to facilitate quicker and more precise diagnoses and disease monitoring. To accomplish these aims, the Wilson laboratory is focused on a multidisciplinary approach that fuses molecular biology, high-performance computing, technology and software development, and CAP-CLIA molecular testing. His laboratory was the first to sequence the complete genome of a cancer patient using next-generation sequencing and to discover genetic signatures relevant to the pathogenesis of the patient’s acute myeloid leukemia diagnosis. Subsequent studies have revealed numerous key characteristics of several adult and pediatric cancer types related to relapse risk, metastatic disease and mechanisms of acquired resistance. At NCH, Dr. Wilson is leading efforts to translate the knowledge and methods from these previous and ongoing studies into comprehensive clinical assays for both cancer and constitutional disease. He has also co-authored numerous articles appearing in such well-known publications as Molecular Cancer Research, New England Journal of Medicine and Cell and is a member of several professional organizations, including the American Society of Human Genetics.
Bradford C. Berk, MD, PhD
Senior Vice President for Health Sciences
University of Rochester Medical Center
Dr. Berk is Professor of Medicine, Cardiology, and Pharmacology and the Senior Vice President for Health Sciences at the University of Rochester. Dr. Berk received his M.D. and Ph.D. degrees from the University of Rochester. He has served on the faculties of Harvard Medical School, Emory University, and the University of Washington. Dr. Berk was previously Chairman of Medicine (1999-2006) and Chief of the Cardiology Unit (1998-2003) at the University of Rochester. In addition he was Director of the Aab Cardiovascular Research Institute. Dr. Berk is a fellow of the American Heart Association and the American College of Cardiology, and a member of the Association of American Physicians. Dr. Berk is past-president of the North American Vascular Biology Organization (NAVBO). He is Consulting Editor for Circulation and Circulation Research and is on the editorial boards of ATVB and the Journal of Clinical Investigation. He serves on the Empire State Stem Cell Board Funding Committee and the National Heart, Lung and Blood Institute (NHLBI), Stem Cell Clinical Trial Network and Gene and Cell-Based Therapies Data and Safety Monitoring Board (DSMB).
His research interests include: molecular biology of renin-angiotensin-aldosterone
system; regulation of endothelial cell function especially by shear stress; the role of oxidative stress in vascular biology and the genetic mechanisms of vascular remodeling. Dr. Berk has published widely – more than 250 articles, chapters, and books.
Michael O’Reilly, PhD
Director, Lung Biology and Disease Program
University of Rochester Medical Center
As a basic scientist trained by physicians, Dr. O’Reilly has a deep appreciation for the importance of integrating basic and clinical research to understand, treat, and prevent disease. His research expertise is on oxygen toxicity to the developing lung, which he leverages in the mentorship of students, in the review of manuscripts for journals, and in NIH study sections. He has a strong and consistent track record of mentoring and training the next generation of physician-scientists. Research from the O’Reilly lab has shown how mitochondrial superoxide produced during hyperoxia damages DNA, thereby activating SMG1 and ATM kinases controlling p53-dependent expression of the cyclin-dependent kinase inhibitor p21. Although p21 is best known for its ability to inhibit proliferation, his lab was the first to show that it protects against oxidative stress independent of cell cycle arrest through maintenance of anti-apoptotic proteins of the Bcl-2 family. P21 has now emerged to be one of the most abundantly expressed genes in many forms of lung injury.
Previous Advisory Board Members
Manuel Serrano, PhD
Institute for Research in Biomedicine Barcelona
Dr. Serrano obtained his PhD in 1991 for his research at the Center for Molecular Biology (CSIC/UAM, Madrid) under the supervision of M. Salas and J.M. Hermoso. From 1992 to 1996 he worked as a Postdoctoral Fellow in the laboratory of D. Beach at the Cold Spring Harbor Laboratory, New York, USA. In 1997, he returned to Spain to start his own research group at the Spanish National Biotechnology Center (CSIC, Madrid). He moved to the Spanish National Cancer Research Center (Madrid) in 2003 to lead the Tumor Suppression Group, where he also served as Director of the Molecular Oncology Program (2012-2017). In May 2017, he relocated to the Institute for Biomedical Research-IRB Barcelona to establish the Cellular Plasticity and Disease Group within the Molecular Medicine Research Program. Dr. Serrano has made several seminal discoveries including the discovery, cloning, and characterization of the tumor suppressor and senescence effector p16INK4a (CDKN2A) and the discovery of developmentally-programmed senescence.