Dr. Bain’s research goal is to improve understanding of how the lung interacts with and employs cellular and humoral elements of innate immunity to combat pathogens and manage injury. He is currently focused upon two research questions. First, how do platelets and platelet factors attenuate lung injury during pathogen-mediated lung injury with particular attention to the role of platelet released factors in providing protection to alveolar epithelium? Second, what are mechanisms by which alternative complement pathway function supports host defense and patient survival during critical illness with acute respiratory failure?

Mehret Birru Talabi, MD PhD is a physician investigator in rheumatology and clinical immunology. She is a graduate of Kenyon College, and received her MD, PhD in Epidemiology, and internal medicine and rheumatology subspecialty training at the University of Pittsburgh and at UPMC. Her research focuses on the intersection of rheumatology and women’s health, with a specific interest in enhancing reproductive outcomes among people with rheumatic diseases. She is an Assistant Dean and Co-Director of the Medical Scientist Training Program (MSTP) in the School of Medicine and is the associate program director of the UPMC rheumatology fellowship. 

Dr. Braganza-Jardini’s research seeks to understand the role of the mitochondria and the ubiquitin-proteasome system (UPS) of platelets in aging. Andrea hypothesizes that aging induces changes in the expression of a key mitochondrial protein, mitofusin-1 (MFN1) than in turn produces increased mitochondrial reactive oxygen species (mtROS) and modulates the function of the UPS to enhance platelet activation and lead to an increased risk of thrombosis. In addition to studying the changes in these pathways in platelets from young and old human subjects, she has created a novel MFN1^-/- platelet-specific mouse model from which she will isolate platelets and modulate their function to determine how loss of MFN1 directly affects platelet activation and aggregation. Andrea hopes that the results from these studies can be translationally used to treat and prevent age-related thrombosis.

My research focuses on understanding and targeting the cancer supporting stromal tissues which are critical to the survival, growth and spread of ovarian cancer. Specifically, my lab studies a critical non-malignant component of the ovarian cancer microenvironment, the carcinoma-associated mesenchymal stem cell (CA-MSC). CA-MSCs are stromal progenitor cells which significantly increase cancer growth, enrich the cancer stem cell pool and increase chemotherapy resistance.
My lab studies how CA-MSCs are formed and develop tumor supporting properties. My lab also focuses on identifying important tumor cell:CA-MSC interactions which mediate CA-MSC’s pro-tumorigenic functions and have potential for translation into new therapeutic targets. Additionally, we study how CA-MSCs impact the development of ovarian cancer metastasis and the metastatic microenvironment.
The ultimate goal of my research is to translate novel laboratory findings into powerful therapeutic approaches for the prevention and treatment of ovarian cancer.

Dr. Eisele’s research focuses on age-related protein misfolding disorders like Alzheimer’s disease and transthyretin-related amyloidoses. In these diseases, the misfolding of specific proteins on one hand leads to the loss of the normal function of these proteins, but on the other hands also to aberrant interactions of the misfolded proteins with normal cellular function, which ultimately leads to the degeneration of affected tissue. Therefore, Dr. Eisele investigates what factors favor protein misfolding, how exactly the misfolding occurs and what cytotoxic consequences arise from it. A particular focus is on so-called oligomers, i.e. smaller protein aggregates that are presumably particularly cytotoxic when formed. Ongoing projects focus on cardiac transthyretin-related amyloidosis, transthyretin-related cerebral amyloid angiopathy and delineating cytotoxic consequences of Abeta oligomers in the context of Alzheimer’s disease.

Dr. Evankovich studies the molecular biology of lung injury. His laboratory is interested in the intersection of three molecular systems in the innate immune system, and how they influence inflammation and cell death pathways in the lung. The molecular systems are Damage Associated Molecular Patterns (DAMPs), DAMP Receptors, and the Ubiquitin/Proteasome System (UPS).

Dr. Evankovich’s prior work has identified how several novel DAMP/DAMP receptor pairs are processed for disposal in the UPS, and how this process can be manipulated to change subsequent cellular responses. For damaging responses, increasing targeted DAMP receptor disposal through the UPS could lessen organ damage; likewise, for protective DAMP/DAMP receptor pairs, reducing disposal in the UPS could be therapeutic to reduce injury.

Teaming with the Small Molecule Therapeutics Center, Dr. Evankovich’s future work aims to discover novel small molecules to disrupt these pathways and test in preclinical models of lung injury. He is also an Associate Member of the Aging Institute, where he focuses on the contribution of aging to innate immune responses in the lung.

My research interest lies in infectious complications among immunocompromised hosts, primarily organ transplant recipients and patients with hematological malignancies. My K23 award focuses on the changes in the gut microbiome among lung or liver transplant recipients as they develop colonization or infection with multidrug-resistant organisms. My hope is to use this knowledge to conduct clinical trials of novel therapies such as fecal microbiota transplant or bacteriophages to treat drug-resistant organisms in these patients. I also have an interest in COVID-19 in this patient population, particularly oncology patients who are at risk for protracted SARS-CoV-2 replication and intra-host viral evolution.

Dr. Kliment’s laboratory is interested in identifying new molecular pathways connecting mitochondrial dysfunction with epithelial and innate immune cell function in the pathogenesis of chronic obstructive lung disease (COPD) and pulmonary fibrosis to improve therapeutic options for patients. Our lab specifically studies the role of adenine nucleotide translocase (a canonical mitochondrial ADP/ATP transporter) in the airway and alveolar epithelium of the lung in the context of cigarette smoking-related lung disease and lung fibrosis. We want to better understand how, in health and disease, ANT regulates epithelial function through mitochondrial metabolism and cellular senescence. We have also found that ANT plays a role in airway epithelial homeostasis through surface hydration and the action of tiny motile cilia in the airway. We utilize a repertoire of relevant murine models of injury, molecular genetic approaches, in vitro biochemical assays, and human bio-samples to examine mitochondrial and cell homeostasis in the lung.

My research has focused on the molecular modulation of cardiomyocyte homeostasis and cardiac metabolism. My postgraduate research has been investigating the function of Tead1, a downstream effector of Hippo pathway, where I have identified the imperative roles of Tead1 in the maintenance of normal adult heart contractility. This effort utilized a cardiac-specific inducible Tead1 knock-out allele and demonstrated Tead1’s critical function in sarcoplasmic reticulum Calcium homeostasis (Liu et al., JCI Insight, 2017). In line with the crucial role of Hippo pathway in proliferation, I also demonstrated the requirement of Tead1 in modulating perinatal cardiomyocyte replication (Liu et al., PLos One, 2019). Subsequently, I discovered that mitochondrial dysfunction also underlies an important aspect regulated by Tead1 in the pathogenesis of cardiomyopathy (Liu et al., Am J Physiol Heart Circ Physio, 2020). By extension, my mechanistic studies of Tead1 and its regulation of mitochondrial quality control processes were funded by the American Heart Association’s Career Development Award in 2019 for a three-year period titled “Tead1 as a Novel Regulator of Mitochondrial Function in Cardiomyocytes”.

I started to build my own research team and establish my independent scientific career by exploring regulatory factors of Hippo pathway signaling and interactive factors of Tead1, which led to the discovery of a novel factor—C5x (unpublished). Using conditional C5x cardiomyocyte specific knockout mouse models, my team identified the surprisingly critical functionality of C5x as a modulator of cardiomyocyte turnover and heart size. Given my interests in cardiomyocyte cell cycle progression, hypertrophy, and regeneration, I hope to establish an independent research program based on studies of this novel factor and to explore its therapeutic potential in heart disease.

My research focuses on how the interface between epithelium and sensory neurons regulates bladder homeostasis and activity, and how changes in the properties of these cells can result in organ malfunction. In particular, I am very interested in studying how bacterial infection of the bladder can affect urothelial homeostasis and permeability, and afferent sensory signaling. There is limited knowledge of the molecular mechanisms that drive voiding symptoms and pain in several pathologies that affect the lower urinary tract system. My overall plan is to use a combination of physiological, biochemical, pharmacological and molecular biology techniques to fill this knowledge gap.

Dr. Radomski is an Assistant Professor of Medicine and Clinical & Translational Science within the Division of General Internal Medicine and Center for Pharmaceutical Policy & Prescribing. He is also affiliated with the Pittsburgh VA Center for Health Equity Research and Promotion as a Research Health Scientist. As a practicing general internist and health services researcher, Dr. Radomski’s research focuses on practical and scalable solutions to accurately measure and reduce the delivery of low-value care and how the receipt of care across multiple healthcare systems influences health service utilization, outcomes, and value. He is supported by a K23 Career Development Award from the National Institute on Aging and is also leading a major VA study to evaluate the use and cost of low-value health services by Veterans in VA and non-VA care settings. His research has been published in journals such as JAMA, the Annals of Internal Medicine, and the Journal of the American Geriatric Society. He also serves as the Director of Academic Programs in Clinical Research for the Institute for Clinical Research Education.

Dr. Robinson’s research examines how influenza infection alters the host immune response and increases susceptibility to secondary bacterial and fungal infections in the lung. Specifically, influenza infection results in decreased production of the IL-1 family of cytokines in response to secondary staphylococcal pneumonia, affecting innate immune cell recruitment to the lung. She is actively investigating the mechanisms of decreased neutrophil recruitment to the lung during both post-influenza staphylococcal pneumonia and post-influenza invasive pulmonary aspergillosis.

Dr. Rose’s research interests focus on discovering and developing new human therapeutics. His group is working to identify and develop a novel carbon monoxide poisoning antidote. They are also characterizing the mechanisms of severe CO poisoning from a molecular basis and in novel animal models. Dr. Rose’s research focuses on studying the mitochondrial effects of carbon monoxide and our ability to reverse the toxicity of carbon monoxide in vitro. He also is interested in the clinical and pathological effects of other inhalational lung injuries, such as vaping (e-cigarette, or vaping product-use acute lung injury – EVALI) and halogen gas exposure. He is interested in the drug development process, including nonclinical toxicology, pharmacodynamic and pharmacokinetic assessment, drug manufacturing and clinical study design. Dr Rose also focuses on academic commercialization and innovation. Together with Drs Mark Gladwin and Jesus Tejero, he co-founded Globin Solutions Inc. (https://www.globinsolutions.com). He is co-inventor on eight patents and patent applications.

My research focuses on the role of aging and aging-related conditions in hereditary bleeding disorders, specifically von Willebrand disease and hemophilia. My K23 award explores the effect of aging on von Willebrand factor levels and bleeding phenotype in von Willebrand disease.

Recently, Dr. Snyder identified that lung donor memory T cells, the predominant cell in the adaptive immune system, survive following transplantation and persist for weeks to months in the recipient. Furthermore, this survival of donor T cells is associated with improved short-term outcomes. Additionally, they found that lung allograft-infiltrating, recipient-derived T cells which migrate to the lungs following transplantation take up residency within the lung. His lab is focusing on determining the function and specificity of these tissue-resident memory T cells and if they are contributing to chronic rejection.

In addition to lung transplantation, the Snyder lab is actively investigating the role of tissue resident memory T cells on pulmonary fibrosis and chronic airway inflammation in human lungs.

My research focuses on understanding the role of lysine acetylation, a reversible post-translational modification, in regulating cardiac mitochondrial protein functions. In particular, I seek to investigate the role played by a recently discovered mitochondrial acetyltransferase protein GCN5L1, which promotes lysine acetylation. The focus of my research revolves around understanding the role of GCN5L1 in regulating cardiac substrate utilization, redox homeostasis, mitochondrial bioenergetics, metabolism and autophagy in the aged heart. I hypothesize that GCN5L1 mediated acetylation of cardiac mitochondrial proteins regulates their function. Utilization of acetyl-proteomics coupled with LC-MS/MS will allow us to identify specific lysine sites that potentially regulate mitochondrial protein function and therefore overall cardiac function.

Dr. Zhang is currently studying the mechanism of GCN5L1, a mitochondrial acetyltransferase, in enhancing cardiac bioenergetics through retrograde activation of PGC-1α signaling in response to hemodynamic stress or exercise using cardiac specific GCN5L1 deficient mice.   As a cardiologist subspecializing in advanced heart failure and transplantation, and as a basic scientist studying cardiomyocyte biology, Dr. Zhang’s long-term career goal is to become a physician scientist,  focusing on reciprocal regulation of cardiac epigenetics and metabolism regulation in heart failure and exercise to discover a more effective treatment for heart failure.