Jonathan Alder, PhD Medicine
Assistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Dr. Alder’s research focuses on understanding the role of telomere length in human health and disease. His current interest is exploring the mechanisms by which telomere dysfunction causes age-related lung diseases including pulmonary fibrosis and emphysema. The Alder lab uses a number of approaches to explore that pathogenesis of short-telomere mediated disease including genetics, cell biology, and animal models with the hope that these studies will lead to a deeper understanding of how telomere dysfunction contributes to lung disease and potentially inform rational therapies.
Jessica Bon, MD, MS Medicine
Associate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Director, Pulmonary and Critical Care Medicine Fellowship Program
Dr. Bon’s academic and research interests focus on the investigation of musculoskeletal comorbidities in chronic obstructive pulmonary disease. Dr. Bon’s research has concentrated on the role that inflammation and autoimmunity play in COPD-related bone loss. She has shown that radiographic emphysema independently predicts low bone mineral density in smokers and has identified novel autoimmune responses in smokers that are linked to emphysema-related bone loss.
Steve Chan, MD, PhD Medicine
Professor of Medicine, Division of Cardiology
Director, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute
Director, Center for Pulmonary Vascular Biology and Medicine
Associate Program Director, Fellowship Research, Cardiovascular Fellowship Training Program
Dr. Chan studies the molecular mechanisms of pulmonary vascular disease and pulmonary hypertension (PH), an example of an enigmatic disease where reductionistic studies have primarily focused on end-stage molecular effectors. To capitalize on the emerging discipline of “network medicine,” research in the Chan laboratory utilizes a combination of network-based bioinformatics with unique experimental reagents derived from genetically altered rodent and human subjects to accelerate systems-wide discovery in PH. In doing so, Dr. Chan’s published work was the first to identify the systems-level functions of microRNAs (miRNAs), which are small, non-coding RNAs that negatively regulate gene expression, as a root cause of PH. Dr. Chan also has expertise in the study of extracellular microRNAs and their delivery to recipient tissue for modulation of gene expression. Dr. Chan has a strong track record for training post-doctoral fellows in cardiovascular research, with a number of his trainees going on to establish independent academic research careers as principal investigators.
Toren Finkel, MD, PhD Medicine
Professor of Medicine, Division of Cardiology
G. Nicholas Beckwith III and Dorothy B. Beckwith Chair in Translational Medicine
Director, Aging Institute
Dr. Finkel’s lab is interested in the intersection of metabolism, mitochondrial function and aging. Current projects include the link between impaired autophagy and vascular aging, the molecular basis that regulates mitochondrial calcium entry, the role of fatty acid oxidation in regulating cell fate and the molecular control on mitochondrial turnover.
Daniel Forman, MD Medicine
Professor of Medicine, Division of Geriatric Medicine
Chair, Section of Geriatric Cardiology
Dr. Forman is dually trained in Geriatrics and Cardiology, and holds appointments in both the Geriatrics Research Education and Clinical Center (GRECC) and the Cardiology Division at the Pittsburgh VA. With NIH funding, he is studying the benefit of nitrate capsules for fatigue and function in older adults with heart failure and preserved ejection fraction. In two other NIH projects he is studying the impact of exercise on skeletal muscle gene transcription (Molecular Transducers of Physical Activity in Humans [MoTrPAC]), and the impact of exercise training on cognition (Investigating Gains in Neurocognition in an Intervention Trial of Exercise [IGNITE]). At the VA, he is comparing the impact of different training regimens (strength, aerobic, and inspiratory muscle training) on skeletal muscle morphology, gene expression, and functional capacity. He is also studying the utility of prehabilitation in frail elderly prior to abdominal and cardiothoracic surgery. Finally, he is funded by PCORI to devise novel strategies to improve cardiac rehabilitation, especially methods to improve enrollment, adherence, and value for complex, older cardiovascular patients.
Kevin Gibson, MD Medicine
Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Professor of Medicine, Clinical and Translational Science
Medical Director, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease
Dr. Gibson’s research focuses on clinical pathogenesis interstitial lung diseases including idiopathic pulmonary fibrosis, Sarcoidosis, autoimmune lung disease, and occupational lung disease. Dr. Gibson conducts studies that include early and late phase clinical trials of novel therapeutics in interstitial lung disease, the discovery of biomarkers of disease activity and progression, and clinical translational studies of disease pathogenesis. He has published a number of translational studies to identify unique biomarkers of disease activity in idiopathic pulmonary fibrosis and other interstitial lung diseases, studies of novel interventions in acute IPF exacerbations, as well as studies of gene expression profiling in IPF lungs. He has discovered a number of peripheral blood biomarkers that have been useful predicting disease progression in idiopathic pulmonary fibrosis. He has participated in multinational Studies of the genetics of IPF and Sarcoidosis.
Daniel Kass, MD Medicine
Associate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Director, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease (ILD)
Dr. Kass’s research has focused on two critical areas of fibroblast biology. The first is the differentiation of fibroblasts to the highly contractile and synthetic myofibroblast. This fundamental feature of fibrosis leads to the deposition of matrix and the contraction of the gas exchange units in the lung that characterizes IPF. Dr Kass and his lab have discovered that the receptor for the hormone relaxin, RXFP1, is decreased in IPF. The loss of this receptor has several implications for patients: first, IPF patients with the lowest expression of RXFP1 have the most compromised pulmonary function. Second, these patients may be relatively insensitive to the anti-fibrotic effects of relaxin-based therapies. Relaxin has been shown to reverse many of the pathologic events associated with myofibroblast differentiation. Dr Kass has also focused on the role of fibroblasts as regulators of the degree and extent of inflammation in the lung. To this end, he has focused on the role of twist1, a transcription factor with enriched expression in IPF. Deranged expression of twist1, a well-known inhibitor of NF-kappaB signaling, can lead to dramatic changes in the local inflammatory infiltrate in animal models of pulmonary fibrosis.
Dennis McNamara, MD, MS Medicine
Professor of Medicine, Division of Cardiology
Director, Center for Heart Failure Research
Co-Director, Peripartum Cardiomyopathy Network
Dr. McNamara’s clinical research over the last two decades has focused on the influence of genomics on heart failure outcomes and specifically the impact of therapeutics. He previously served as the core laboratory for the genetic sub-study of the AHeFT multicenter trial (GRAHF1). As principal investigator, he is currently directing GRAHF2, a multicenter NIMHD sponsored pharmacogenetic investigation of 225 African American subjects with chronic heart failure with reduced ejection fraction (HFrEF). In addition, as principal investigator Dr. McNamara directed an NHLBI sponsored multicenter study of peripartum cardiomyopathy (IPAC) involving 100 women at 30 centers, and an earlier NHLBI sponsored investigation of recent onset cardiomyopathy (IMAC) of 373 subjects at 16 centers. He has also previously been the recipient of a K24 (renewed for a total of 10 years of funding) for mentorship of young clinicians as clinical and translational investigators.
Alison Morris, MD, MS Medicine
Professor of Medicine and Chief, Division of Pulmonary, Allergy and Critical Care Medicine
Professor of Immunology and Clinical and Translational Research
Director, Center for Medicine and the Microbiome
Director, HIV Lung Research Center
UPMC Chair in Translational Pulmonary and Critical Care Medicine
Dr. Morris has been PI of 6 NHLBI R01s to investigate lung disease in HIV and the role of pulmonary infections, such as Pneumocystis colonization in HIV-associated COPD, and was a Primary Investigator in the NHLBI-sponsored, “Lung HIV,” a consortium of 8 clinical centers investigating HIV-associated pulmonary disease. Additionally, Dr. Morris was co-PI on a U01 investigating the lung microbiome in the normal host and in HIV-associated COPD, and she participated as one of 6 sites in the Lung HIV Microbiome Program. Key scientific discoveries include the prevalence of diffusing capacity abnormalities in HIV, the role of colonizing infections in lung dysfunction, determining the associations of COPD and pulmonary hypertension in HIV, phenotyping lung disease in HIV, and linking lung function abnormalities to systemic and lung inflammation. Multiple NIH grants and training opportunities have resulted from these cohorts including two K23s, a translational program project grant, an NRSA, and an R34. She holds a K24 mentoring grant, is Vice Chair of Clinical Research in the Department of Medicine, serves as training faculty on several T32s, and runs a grant writing course. She also supervises pulmonary function testing in the MACS and WIHS cohorts.
Enrico Novelli, MD, MS Medicine
Associate Professor of Medicine, Division of Hematology/Oncology
Section Director, Benign Hematology
Dr. Novelli’s research has focused on the mechanisms underlying vascular dysfunction in SCD via three main projects: 1) Dr. Novelli has explored the role of the protein thrombospondin-1 in SCD. He has found that elevated plasma levels of TSP1 in several large cohorts of patients with SCD are associated with vaso-occlusive complications and identify a subset of patients who display hemostatic activation and have a more severe phenotype. In translational studies presented as podium talk at the American Society of Hematology Annual Meeting he also found TSP1 to cause pulmonary hypertension in transgenic mice by binding to its receptor CD47. 2) Another line of research has focused on the characterization of arterial stiffness as a mechanism of vascular dysfunction in SCD. Dr. Novelli has discovered a new link between hemolysis and arterial stiffness by showing that hemolysis is independently associated with arterial stiffness measured by pulse pressure in a large cohort of SCD patients. This discovery is of high clinical relevance as it suggests that elevated hemolysis rates encountered in a subset of SCD patients may lead to an increased risk of vascular complications; 3) Most recently, Dr. Novelli has turned his attention onto the cerebral vasculature in SCD in an effort to elucidate SCD-related cognitive impairment. He has discovered a neuroimaging marker of small vessel disease associated with cognitive function in SCD.
Solomon Ofori-Acquah, PhD Medicine
Associate Professor of Medicine, Division of Hematology-Oncology
Associate Professor of Human Genetics
Principal Investigator, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute
Dean, School of Biomedical and Allied Health Sciences, University of Ghana
Classically trained as a hematology and molecular genetics scientist in the National Health System in England, Dr. Ofori-Acquah described the RFLP haplotype of the sickle chromosome among sickle cell disease (SCD) patients in England for the first time and determined the functional relevance of polymorphism of a short tandem repeat in the beta-globin locus control region on HbF level in SCD. His expertise in functional genomics was central to defining the role of a polymorphic cyclic AMP response element in the gamma globin gene in induction of HbF3. Currently, Dr. Ofori-Acquah’s research ranges from basic and translational studies in animal models to large-scale genomics studies of SCD patients in the H3Afrcia consortium. His studies on Nrf2 indicate that this transcription factor plays a dominant role in slowing down progression of SCD with aging. Thus, Nrf2 is an attractive therapeutic target for lessening the severity of SCD chronically. The Ofori-Acquah lab has also recently found that by promoting “low-grade” disease phenotype, Nrf2 activation protects transgenic SCD mice from developing acute lung injury during episodes of hemolytic crisis.
Sanjay Patel, MD, MS Medicine
Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Director, Center for Sleep and Cardiovascular Outcomes Research
Medical Director, UPMC Sleep Laboratory
Dr. Patel is a physician scientist focused on sleep epidemiology, particularly on the impact of sleep apnea on cardio-metabolic outcomes. As the Director of the new Center for Sleep and Cardiovascular Outcomes Research at the University of Pittsburgh, he is building a program that aims to understand the ability to improve health outcomes through sleep-focused interventions. Among his interests are using electronic health records to study relationships between obstructive sleep apnea and the development of cardiovascular diseases, studying the impact of obstructive sleep apnea treatment on patients with diabetes, and improving care delivery models for sleep care. Dr. Patel is deeply committed to mentoring the next generation of scientists, having mentored trainees at all levels from high school students to junior faculty in his laboratory, as well as having chaired an annual 2.5-day program on mentoring young investigators in sleep medicine sponsored jointly by the American Academy of Sleep Medicine and the National Heart Lung and Blood Institute.
Margaret Ragni, MD, MPH Medicine
Professor of Medicine, Division of Hematology-Oncology
Professor of Clinical and Translational Science
Director, Hemophilia Center of Western Pennsylvania
Throughout her career, Dr. Ragni has been involved in clinical translational studies relevant to congenital hemostatic and thrombotic disorders including the effects of HIV in hemophilia. She has served as the chair of clinical trials, prospective epidemiologic, observational, case-control studies, cost-effectiveness analyses, and investigator-initiated new drug trials in hemophilia and Von Willebrand disease (VWD). Dr. Ragni’s studies were among the first multi-center NIH-funded investigator-initiated studies in hemophilia malignancy (NCI), hemophilia inhibitor formation (NHLBI), hemophilia HIV/HCV infection (NHLBI), hemophilia AIDS therapy (NIAID), and hemophilia adult prophylaxis (NHLBI). Additionally, she has served as Co-Chair for State of the Science SOS Hemophilia & VWD Subcommittee to design future trials, three funded by NHLBI. Dr. Ragni has collaborated on multi-center organ transplant HIV trials (NIAID), hemophilia gene therapy trials (NHLBI); VWD genotype-phenotype studies (NHLBI); extended half-life protein trials for hemophilia; and rhIL-11 and recombinant VWF for VWD. She serves as medical director of the Hemophilia Center of Western PA, and member of the National Hemophilia Foundation Medical & Scientific Advisory Committee. Moreover, Dr. Ragni also collaborates with the Multicenter AIDS Cohort study with Dr. Rinaldo to examine VWF and endothelial dysfunction and cardiovascular disease in HIV.
Charles Rinaldo, PhD Medicine
Dr. Rinaldo’s basic research laboratory focuses on studies of innate and adaptive immunity in the immunopathogenesis of HIV and human herpesvirus 8 (KSHV) infections linked to the Multicenter AIDS Cohort Study and AIDS Clinical Trials Group (ACTG). Dr. Rinaldo also directs an Immunology Specialty Laboratory in the ACTG focused on cell immunity, regulation and immune activation in the ACTG HIV Reservoirs, and Viral Eradication Transformative Science Group. His HIV research centers on the dynamics of dendritic cell-T cell interactions leading to anti-HIV immune reactivity as a model for immunotherapy of antiretroviral drug treated HIV-1 infected persons, with the ultimate goal of eradicating their HIV reservoir. Dr. Rinaldo’s clinical specialty is diagnostic virology, with emphasis on molecular methods for rapid detection of herpesvirus and influenza virus infections. He has primary responsibility for diagnostic molecular virology in the UPMC Clinical Microbiology Laboratory that serves over 30 regional hospitals and associated clinical sites and has advised numerous postdoctoral fellows and graduate students in these areas of research.
Liza Villanueva, MD Medicine
Professor of Medicine, Division of Cardiology
Director, Center for Ultrasound Molecular Imaging and Therapeutics
Vice Chair for Pre-Clinical Research, Department of Medicine
Dr. Villanueva’s research focuses on the development of medical diagnostic and therapeutic strategies based on ultrasound and ultrasound contrast agents (gas-filled microspheres, or microbubbles). Her work has consistently bridged fundamental imaging sciences with translational biomedical research. As an Established Investigator of the American Heart Association, she has been a leader in the development of microbubbles for the assessment of myocardial perfusion and ultrasound molecular imaging with targeted microbubbles for the detection of inflammatory and angiogenic endothelial markers in pre-clinical models of heart disease. The Villanueva lab has pioneered the development and application of microbubbles as molecular probes and acoustic detection strategies for optimizing imaging sensitivity. They have applied fundamental principles of ultrasound and the physics of microbubble acoustic behaviors to develop novel targeted molecular therapeutics, whereby nucleic acid loaded microbubbles (siRNA, miRNA, plasmid), in the presence of precisely tuned ultrasound, selectively enhance membrane permeability and deliver payloads to the target site. These studies are conducted at the Center for Ultrasound Molecular Imaging and Therapeutics, a translational multidisciplinary research facility that epitomizes the reciprocal relationship between imaging sciences and biomedical translational research.
As the founding Director of the Center for Ultrasound Molecular Imaging and Therapeutics and Director of Non-Invasive Cardiac Imaging for the Heart and Vascular Institute at UPMC, Dr. Villanueva has continuous exposure to a pool of outstanding trainees and is deeply committed to mentoring them as future clinical and basic translational scientists. She has mentored MD and PhD post-docs (AHA fellowships, NRSA, international grants); medical students (Clinical Science and Physician Scientist Training Programs at the University of Pittsburgh; Howard Hughes Medical Institute); undergraduates (Independent Study); and high school students (summer research) throughout her 23-year career. Additionally, she has served or actively serves on 9 PhD committees and is a Training Faculty member on 4 T32s at the University of Pittsburgh, including serving as program director for a cardiology imaging T32.
Charlene Chu, MD, PhD Pathology
Professor of Pathology
A. Julio Martinez Chair in Neuropathology
Dr. Chu’s laboratory studies the role of protein kinases in mitochondrial and neurodegenerative diseases, with an emphasis on autophagy and mitochondrial homeostasis. She has 30 years of research experience with cell signaling, proteolysis and post-translational protein modifications, with additional expertise in diagnostic vascular pathology and neuropathology as a practicing pathologist. In 2009, Dr. Chu completed a 2-year sabbatical in mass spectrometry and phosphoproteomics, funded by a NIH K18 Established Researcher Career Enhancement Award. Using cell biology, molecular imaging and mass spectrometry, her team identified novel phosphorylation sites of the major autophagy protein LC3, the mitochondrial transcription factor TFAM, and the mitochondrial calcium antiporter NCLX, each of which modulates cellular injury. Dr. Chu also discovered a basic mechanism by which damaged mitochondria are recognized for autophagic clearance, based on redistribution of the inner mitochondrial membrane phospholipid cardiolipin. A major area of interest in the laboratory concerns the role of the mitochondrial kinase PINK1 in CNS and pulmonary epithelial/endothelial systems, discovering novel mechanisms by which mitochondria release signals to promote cell growth. A new area of interest involves creating and using iPSC models of mitochondrial or age-related diseases. In collaboration with pulmonary colleagues, the Chu lab discovered a small molecule that increases PINK1 to rescue in models of neurodegenerative, inflammatory and pulmonary diseases.
Youhua Liu, PhD Pathology
Professor of Pathology, Division of Experimental Pathology
UPMC Endowed Chair in Tissue Biology
Studies in Dr. Liu’s laboratory are focused on dissecting the cellular and molecular pathways leading to chronic renal fibrosis, and exploring novel strategies for therapeutic interventions. Using a series of experimental approaches, we are addressing several fundamental issues in renal fibrosis, such as what types of cells produce a large amount of matrix proteins under pathologic conditions and how they are regulated. Current studies in our laboratory include: 1) to decipher the mechanisms controlling tubular epithelial-mesenchymal cross-talks (EMC) in renal fibrogenesis; 2) to dissect several key signal pathways such as Wnt/beta-catenin and hedgehog in the pathogenesis of renal fibrosis; 3) to elucidate the patho-mechanisms of podocyte injury and proteinuria; 4) to develop novel therapeutic strategies aimed at ameliorating renal fibrosis and kidney dysfunction.
Peter Lucas, MD, PhD Pathology
Professor of Pathology, Divisions of Molecular Genomic Pathology and Experimental Pathology
Professor of Pediatrics
Vice Chair for Translational Pathology Imaging
Dr. Lucas is a physician scientist, directing a laboratory that focuses on the relationship between chronic inflammation and the development of vascular, metabolic, and neoplastic diseases. Specifically, his lab focuses on the role of an NF-κB signaling pathway that is controlled by the “CBM signalosome,” a complex of three proteins (CARMA, Bcl10, and MALT1). Dr. Lucas’s lab originally identified this signalosome in lymphocytes, where it mediates NF-κB activation in response to antigen receptor ligation, and plays a critical role in the immune response. More recently, his group has found that an analogous signaling pathway operates outside the confines of the immune system, in epithelial and mesenchymal cells, where it promotes pro-inflammatory responses that contribute to a range of disease processes.
Tim Oury, MD, PhD Pathology
Professor of Pathology, Division of Molecular Genomic Pathology
Dr. Oury is investigating a novel role for the Receptor for Advanced Glycation Endproducts (RAGE) in the pathogenesi s of asthma. His lab has found that RAGE is necessary for initiating innate immune responses that then promote the pathogenesis of asthma. Specifically, he has found that RAGE mediates lung specific recruitment of group 2 innate lymphoid cells (ILC2) in response to allergens and is currently investigating the mechanisms in which RAGE is medicating this process.
Ivona Pandrea, MD, PhD Pathology
Professor of Pathology
Professor of Infectious Diseases and Microbiology
During the last 17 years, Dr. Pandrea has developed numerous new animal models for the study of progressive, nonprogressive, and elite controlled SIV infections. Her research in non-human primate (NHP) models of AIDS resulted in the development of new paradigms of SIV pathogenesis. Supporting Dr. Apetrei, Dr. Pandrea’s laboratory was involved in the only large-scale studies assessing the biology of SIV in the wild and the main modalities of SIV transmission in natural hosts. During the last years, she has performed NHP studies with multiple therapeutic interventions, including antibiotics or various diets, whose impact on the NHP microbiome was monitored. These studies pointed to differences in the microbiome between AGMs and macaques. The Pandrea laboratory developed the needed tools for the study of SIV pathogenesis and transmission in AGMs, with a focus on mucosal sites. She has also investigated the role of microbial translocation and inflammation in HIV-associated co-morbidities including cardiovascular disease and hypercoagulability. Additionally, Dr. Pandrea has a strong history of training and mentoring both graduate and medical students, as well as postdoctoral fellows.
Alan Wells, MD, DMSc Pathology
Executive Vice-Chairman, Section of Laboratory
Medical Director, UPMC Clinical Laboratories
The Wells Laboratory research program, in close collaboration with its research partners, aims to understand cell migration in terms of how motility processes are regulated, and understand how this regulation of migration plays a role i n physiologic and pathologic situations. We are integrating the knowledge gained from our biochemical and biophysical mechanistic studies into our investigations concerning conditions of dysregulated (tumor invasion) and orchestrated (wound healing and organogenesis) cell motility. As part of understanding the motility response, we are investigating both how this particular integrated cell response is selected from among others and the metabolic consequences of motility. This integrative approach provides reinforcing insights and novel avenues for exploration into the basic signaling pathways as well as functioning of whole organism. As a model system, we explore motility signaling from the epidermal growth factor receptor (EGFR) in adherent cells. EGFR plays a central role in the functioning in a wide variety of both stromal and epithelial tissues, and is the prototype for other receptors with intrinsic tyrosine kinase activity. Thus, these studies should have widespread implications.
The two central foci are tumor progression and wound repair. In tumor progression, we examine breast and prostate carcinoma invasion and metastases in terms of molecular signals and the special micro-environments. For this, the laboratory uses human tissues, animal models, and a unique 4-dimensional liver microtissue. In would repair, the current model system is skin wound healing, in which the communications between the epidermis, dermis, and blood vessels is parsed at the molecular levels. The role of stem cells in the natural repair process and as a rationale therapeutic is also being investigated. These two areas are re-inforcing as many of the key molecules and cellular processes are part of the generalizable onco-fetal-wound program.
John Alcorn, PhD Pediatrics
Associate Professor of Pediatrics, Division of Pulmonary Medicine, Allergy and Immunology
John F. Alcorn studied the role of type 17 immunity in viral and bacterial pneumonia. His studies have focused on influenza A infection and suppression of type 17 immunity against secondary staph ylococcal infection. He studied the mechanisms of asthma and allergic airway disease with an emphasis on the role of type 17 cellular immunology. His studies suggested that disease induced by Th17 cells is steroid resistant and may represent a model for steroid-insensitive asthma.
Juan Celedón, MD, DrPh Pediatrics
Niels K. Jerne Professor of Pediatrics
Professor of Internal Medicine, Epidemiology, and Human Genetics
Division Chief, Pediatric Pulmonary Medicine, Allergy, and Immunology
Director, Pediatric Asthma Center, UPMC Children’s Hospital of Pittsburgh
Juan C. Celedón’s research focused on identifying genetic and epigenetic factors and early-life environmental exposures that influence the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) in general and among ethnic minorities in particular.
Cheryl Hillery, MD Pediatrics
Clinical Director, Pediatric Hematology, UPMC Children’s Hospital of Pittsburgh
Director, Comprehensive Pediatric Sickle Cell Program
Professor of Pediatrics, Division of Hematology/ Oncology
Dr. Cheryl Hillery is an NIH-funded physician-scientist who treats patients with sickle cell disease (SCD) and has been involved with basic and translational research programs focused on the vascular and organ pathologies in human and mouse models of SCD as well as novel mechanisms of pain. Hillery’s team studies are trying to discern the exact role of the clotting and inflammatory pathways and to determine whether agents that thin the blood or decrease inflammation may help patients who suffer from SCD. Additionally, Dr. Hillery and her collaborator, Cheryl Stucky, study the precise nerve cells and pathways that sense the pain and carry the message to the brain so that they can develop new methods to treat SCD more safely and effectively. In ongoing studies, Dr. Hillery is also collaborating with Kirkwood Pritchard in exploring the role of high-mobility group box 1 (HMGB1), a nuclear protein that is important for maintaining DNA structure and function.
Bernhard Kühn, PhD Pediatrics
Mellon Scholar, Richard King Mellon Foundation Institute for Pediatric Research
Associate Professor of Pediatrics
Director of Research in Cardiology, Department of Pediatrics
The research laboratory that Bernhard Kühn directs has three interconnected goals: to understand the mechanisms of growth and regeneration in the heart; to provide mechanistic explanations for the huge differences in regenerative activity that exist in biology; and, drawing on the answers to these two fundamental questions, to conduct translational research for the diagnosis and treatment of heart muscle diseases. Prior to Kühn’s work, it was commonly thought that heart muscle cells, cardiomyocytes, are in irreversible proliferative arrest after birth and that myocardial regeneration cannot be increased in mammals. Physicians and scientists were skeptical that it would be possible to stimulate cardiomyocyte proliferation after birth, let alone that this mechanism would regenerate myocardium. Kühn is credited with demonstrating that the postnatal mammalian heart has cardiomyocytes that can be stimulated to divide and that this process gives rise to myocardial regeneration. Kühn has developed an approach of using extracellular factors to stimulate cardiomyocyte proliferation. A peptide of periostin, a component of the extracellular matrix, stimulates cardiomyocyte proliferation and myocardial regeneration in a rat model of myocardial infarction. This work was published in Nature Medicine in 2007. Kühn followed up this seminal study with large-animal experiments published in 2012.
Philana Ling Lin, MD, MSc Pediatrics
Associate Professor of Pediatrics, Division of Infectious Diseases
Dr. Lin has 14 years of research experience in the immunology and pathogenesis of M. tuberculosis infection and has been directly involved in the development and use of the non-human primate model to better understand human M. tuberculosis infection. Dr. Lin’s work includes examining the early events during acute M. tuberculosis infection from both the host and pathogen standpoint, host immune specific factors that control and maintain latent infection, SIV-TB co-infection, drug treatments against TB, vaccine trials and immune control and biomarkers of reactivation. She has been involved in teaching and training undergraduate students, graduate students, post-doctoral candidates, medical students, resident and fellows both at the bench, in the classroom and at the bedside. As the Program Director for the Pediatric Infectious Diseases Fellowship program at the Children’s Hospital of Pittsburgh for 4 years, Dr. Lin is actively involved in mentoring pediatric fellows.
John Williams, MD Pediatrics
Chief, Division of Infectious Diseases
Professor of Pediatrics
Faculty Member, Graduate Programs in Molecular Virology and Microbiology and Immunology
Affiliate, Center for Vaccine Research
Dr. Williams is an international authority on the epidemiology, immunity, and pathogenesis of respiratory viruses. The focus of his laboratory’s research is the pathogenesis and immunity of human metapneumovirus (HMPV) and other respiratory viruses. The work in Dr. Williams’ laboratory has explored multiple aspects of HMPV, including epidemiology of HMPV. His laboratory discovered that RGD-binding integrins are receptors for cellular entry of HMPV via endocytosis and identified the HMPV fusion protein as the sole target of protective antibodies. Williams’ work has led to vaccine candidates and antibodies. In recent years, his laboratory found that HMPV and other acute respiratory viral infections cause impairment of lung CD8+ T cells via PD-1 signaling, a pathway that had previously been associated with chronic infections and cancer.
Deepika Mohan, MD Surgery
Clinical Assistant Professor of Surgery
Dr. Mohan is a trauma surgeon, intensivist, and health services researcher who studies how doctors think. Her goal is to improve the quality of care provided to patients with critical illness by understanding decisions that occur under conditions of time-pressure and uncertainty. Through a mentored research career development award from NIGMS, she has gained experience in using different quantitative and qualitative methods to study variation in physician decision making (e.g., secondary analysis of administrative data, survey instruments, simulation, semi-structured interviews). This work led to some of the first empirical evidence that heuristics (intuitive judgments) play a role in variation in trauma triage, and resulted in multiple publications in well-respected peer-reviewed journals, including Annals of Surgery, PLoS One, and Medical Decision Making. Work from that award also allowed Dr. Mohan to compete successfully for a DP2 grant from the NIH’s Office of the Director to develop a novel intervention to recalibrate physician heuristics in trauma triage. This grant is awarded each year to 30 early stage investigators who propose “high risk/high reward” research programs.
Mackie Neal, MD Surgery
Roberta G. Simmons Assistant Professor of Surgery
Dr. Neal is a surgeon-scientist with a clinical practice consisting of trauma, emergency general surgery, and surgical critical care as well as a translational research interest in hemostasis and thrombosis. His basic science laboratory focuses on understanding the mechanisms of hemostasis and coagulation following trauma and hemorrhagic shock with a specific interest in the impact of sterile inflammation on platelet function. Uncontrolled hemorrhage is the leading cause of preventable death in trauma, which accounts for nearly 10% of annual mortality worldwide. Over 25% of severely injured patients will present with impaired coagulation which increases morbidity and mortality. Although it is well known that trauma results in a profound inflammatory response driven by innate immune activation, the mechanisms of this acute coagulopathy of trauma are poorly understood. The Neal lab has recently discovered a potential link between sterile inflammation and impaired coagulation through expression of the innate immune receptor, toll-like receptor 4 (TLR4) and the endogenous danger signaling molecule, high mobility group box 1 protein (HMGB1) on platelets, with deranged signaling leading to microvascular thrombosis and organ injury. He is testing multiple drug targets for regulating innate immune signaling and attenuating platelet dysfunction following trauma. Dr. Neal also has an interest in targeted platelet therapy and have begun to devise novel platelet specific nanotechnology for drug delivery. He has a multi-disciplinary collaboration combining international experts in platelet biology, coagulopathy, cellular imaging, nanotechnology, biomedical engineering, and innate immune signaling.
Matthew Rosengart, MD, MPH Surgery
Vice Chair of Academic Training
Watson Family Chair in Surgery
Professor of Surgery and Critical Care Medicine
Director, University of Pittsburgh Surgical Critical Care Fellowship Program
Co-Director, University of Pittsburgh Department of Surgery, Surgical Outcomes Research Center
The Rosengart Lab has a long-standing record of examining the role of innate immunity in the systemic response to injury and infection, with particular expertise in calcium-dependent mechanisms. The laboratory has focused upon the mechanisms involved in the inflammatory processes that define the response to injury in relevant sepsis and trauma models such as LPS-induced inflammation and organ dysfunction, cecal ligation and puncture (CLP) polymicrobial sepsis, warm hepatic ischemia/reperfusion (I/R) injury, and hemorrhagic shock. By employing diverse strategies such as in vivo siRNA to generate genetically engineered mice lacking key components of the calcium-sensitive CaMK cascade, high-speed depth resolved optical mapping of calcium transients, electron and fluorescent microscopy of subcellular organelle and protein trafficking, and study of the ramifications of calcium supplementation on inflammation and organ dysfunction, Dr. Rosengart has contributed to the understanding of calcium-dependent regulation and signaling during the inflammatory states of sepsis and injury. The translational perspective of his studies has provided mechanistic insight into the ramifications of the common practice of calcium supplementation in critical illness on the clinically relevant outcomes of organ failure and survival.
Melanie Scott, MD, PhD Surgery
Associate Professor of Surgery
Director of Graduate Education for Surgery Research
Dr. Scott’s research interests involve investigating innate immune responses after surgery, trauma, hemorrhagic shock and infection. Her main research focus is the role of the inflammasome and inflammatory caspases on cell death and survival pathways during surgery and trauma. This work centers on elucidation of novel pathways of inflammasome activation and function in the liver, and how mitochondria are central to these responses in both sterile and infectious tissue injury. She is also very interested in the different ways inflammasomes are activated in multiple cell types in a cell type-specific manner and how these varying responses help coordinate inflammatory responses to host stress and infection. She is also working on a project that investigates the role of pattern recognition receptors, danger signals and inflammasomes in models of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Dr. Scott has multiple collaborations with other PIs in the department, within the university and also at other instituations, which allows her to work on the role of inflammasomes in varying model systems such as tick-borne Ehrlichia infection (a collaboration with Dr. Nahed Ismail in the Department of Pathology), and sickle cell disease (a collaboration with Dr. Prithu Sundd in the Vascular Medicine Insititute).
Jason Sperry, MD, MPH Surgery
Professor of Surgery and Critical Care Medicine
Director, Acute Care Surgery Fellowship
Dr. Sperry is a Professor with a primary appointment in the Department of Surgery, Division of Trauma and General Surgery and secondary appointments in the Department of Critical Care Medicine and the Clinical and Translational Science Institute (CTSI) at the University of Pittsburgh.He is a physician trained in general surgery and surgical critical care with a masters’ degree in public health. Dr. Sperry’s research focuses on the elucidation of the mechanisms that are responsible for sex-based outcome differences following injury, clinical outcomes following traumatic injury (primarily on massive transfusion), prehospital resuscitation, early correction of the coagulopathy that complicates injury, and the ability to predict a complicated post-injury course in the early prehospital and trauma bay setting. He is the principal investigator (PI) for the Linking Investigations Trauma and Emergency Services (LITES) network funded by the U.S. Department of Defense and PI of the PAMPer trial and STAAMP trials funded by the Prehospital Use of Plasma in Traumatic Hemorrhage (PUPTH) program and the Tranexamic Acid Clinical Research (TACR) program, under the direction of the Department of the Army.He is a co-investigator for the Trans-Agency Research Consortium for Trauma-Induced Coagulopathy (TACTIC) funded thru NHLBI, as well as multiple other NIH-funded grants. His overarching goal is to improve outcomes following traumatic injury.
Edith Tzeng, MD Surgery
UPMC Professor of Surgery
Chief of Vascular Surgery, VA Pittsburgh Healthcare System
Dr. Tzeng’s research focuses on vascular related topics. She has a strong focus on translational studies of vascular healing and wound healing. The effect of small molecules such as carbon monoxide and nitric oxide on the prevention of intimal hyperplasia is an active area of research with an attempt to understand the mechanisms by which these molecules achieve their benefit in the vasculature. Related to vascular healing is cutaneous wound healing. The beneficial effects of CO and NO have also been shown in cutaneous wound healing and efforts are ongoing to better evaluate these effects. The ultimate goal of her research is to bring these agents to clinical application.
Brian Zuckerbraun, MD Surgery
Chief, Division of General Surgery
Professor of Surgery
The Zuckerbraun Lab primarily investigates the acute inflammatory response in the liver and vasculature following injury from trauma/hemorrhagic shock, sepsis, or direct vascular injury. Much of the work has focused on the role of gaseous signaling molecules, including nitric oxide and carbon monoxide. Specifically, they have been investigating the induction of adaptive signaling pathways and how these molecules regulate mitochondrial responses to these stresses to influence immunity and inflammation.