Patrick Belvitch, MD (Vascular Diseases, ALI/ARDS)
Dr. Belvitch focuses his research on the cellular mechanisms responsible for endothelial barrier function under physiological and pathophysiological conditions, particularly acute lung injury. Specifically, he is interested in the regulation of the actin cytoskeleton and its contribution to endothelial barrier integrity through changes in cell shape and cell membrane dynamics. His lab employs a variety of biochemical assays, cell culture techniques and animal models of lung injury to better understand the pathophysiology of this syndrome with the hope of identifying new therapeutic targets.
Steven Dudek, MD (Vascular Diseases, ALI/ARDS)
Research in Dr. Dudek’s lab focuses on EC barrier regulation in ALI/ARDS. He has published extensively in this area and has identified essential roles for multiple cytoskeletal proteins and signaling pathways in the regulation of vascular permeability by multiple agonists and compounds. In particular, his group has characterized extensively the barrier enhancing properties of agonists such as sphingosine 1-phosphate (S1P) as well as the regulation and function of key EC cytoskeletal proteins in this process, including cortactin, nonmuscle myosin light chain kinase, and c-Abl. They have utilized novel imaging techniques to investigate the hypothesis that key EC cytoskeletal proteins (e.g., cortactin) regulate dynamic EC structural rearrangements that result in altered barrier function during ALI syndromes. This approach correlates biomechanical properties with ultrastructural information to provide unique insights into the regulation of this essential process. In addition, Dr Dudek has employed multiple cell culture and animal models of sepsis and ALI as well as translational studies of genomic associations with multiple pulmonary diseases (e.g., ALI, asthma, etc), including functional SNP analyses, to provide further pathophysiologic insights. They have synthesized the knowledge gained from all of these approaches to actively screen barrier-promoting agents for development of optimal therapeutic compounds to reverse pathologic vascular leak and to explore the therapeutic potential of S1P-related FTY720 analogs both in vitro and in preclinical animal models of ALI/ARDS.
Dustin Fraidenburg, MD (Vascular Diseases, ALI/ARDS, Pulmonary Hypertension)
Dr. Fraidenburg’s research focuses on understanding the pathobiologic mechanisms of pulmonary vascular dysfunction in both acute and chronic lung disease with a specific focus on lung inflammation and hypoxemia. Lung inflammation and hypoxemia are major risk factors for mortality in acute respiratory distress syndrome (ARDS) and play important roles in the development and progression of pulmonary hypertension (PH). Adequate blood oxygenation is dependent on effective matching of ventilation and perfusion in the lung microenvironment and, as an evolutionary mechanism, hypoxic pulmonary vasoconstriction is aimed at maintaining sufficient blood supply to the most effectively ventilated areas of the lung. This process has been shown to be dysfunctional in numerous acute and chronic respiratory disorders with important implications for morbidity and mortality. The work in Dr. Fraidenburg’s lab is focused on determining the mechanisms by which NFAT, an important inflammatory signaling pathway, leads to impaired hypoxic pulmonary vasoconstriction during acute lung inflammation and injury as well as its potential role in pulmonary arterial hypertension.
Patricia Finn, MD (Lung Immunology, Transplantation, Lung injury, Asthma)
Dr. Finn’s research is primarily focused on the investigation of immune mediated pulmonary diseases. Specifically, her laboratory analyzes mechanisms of T lymphocyte activation and in the development of pulmonary inflammatory disorders (e.g. transplantation, lung injury and asthma), as well as the interface between the innate and adaptive immune systems. She focuses on translational investigations and molecular biological studies in murine models (in vitro and in vivo) as well as human clinical studies. As additional methods to identify key regulatory immune pathways, Dr. Finn’s laboratory is also furthering the analysis of inflammatory models (transplantation, acute lung injury), incorporating bioinformatics approaches. In collaboration with Dr. David Perkins in the Department of Surgery, Dr. Finn has expanded her interests to include the effect of the microbiome in pulmonary disorders.
Jeffrey Jacobson, MD (Vascular Diseases, ALI/ARDS, Pulmonary Fibrosis)
As a pulmonary and critical care physician-scientist, Dr Jacobson has specific research interests in cell and animal models of acute lung injury (ALI) and ventilator-induced lung injury. Most recently, his research has focused on mechanisms of the role of integrin β4 (ITGB4) vascular inflammatory responses. His lab was the first to characterize ITGB4 as an inflammatory mediator in both cell and pre-clinical models of inflammatory lung injury. Additionally, they have identified a novel ITGB4-mediated signaling pathway that regulates lung EC barrier enhancement induced by sphingosine 1-phosphate and hepatocyte growth factor, agonists that also confer protection in pre-clinical models of ALI. His ongoing research is aimed at understanding mechanisms responsible for ITGB4 regulation of EC signaling and inflammatory responses in an MRSA sepsis model.
H. Ari Jaffe, MD (COPD, Pulmonary Fibrosis)
Dr. Jaffe studies alpha-1 antitrypsin deficiency in homozygotes and symptomatic heterozygotes, COPD, interstitial lung disease including novel therapies for idiopathic pulmonary fibrosis and anti-TNF antibody strategies in sarcoidosis, alternate strategies for sedation in ventilated patients
Min Joo, MD, MPH(COPD, Asthma, Clinical Outcomes)
Dr. Joo is a health services researcher with a primary focus of improving quality of care through guideline implementation in the diagnosis and management of patients with COPD and/or asthma. As a health services researcher, she has experience in conducting qualitative research such as provider and patient focus groups involving spirometry use, communication between patients and providers, and patient experience during transitions in care. Dr. Joo also has experience conducting observational and comparative effectiveness research including clinical trials in patients with chronic pulmonary diseases. She currently has an RO1 funded by the Agency for Healthcare Research and Quality to study the impact of diagnostic error in COPD and asthma in the primary care setting
Jerry Krishnan, MD, PhD (COPD, Asthma, Clinical Outcomes)
Dr. Krishnan is an expert in delivery science, which seeks to identify care strategies that improve quality, outcomes, and value of healthcare. He is Principal Investigator in PCORI-funded clinical effectiveness trials to improve care transitions after hospital discharge (PArTNER), use of supplemental oxygen (PELICAN), care of children with uncontrolled asthma (CHICAGO Trial), and the NHLBI-sponsored AsthmaNet consortium. He is also an investigator in the American Lung Association Airways Clinical Research Centers (ALA-ACRC). The Breathe Chicago Center© (BCC), is a clinical research program within the division of Pulmonary, Critical Care, Sleep and Allergy at the University of Illinois at Chicago. Led by Dr Krishnan, the BCC conducts health services research and clinical trials that are aimed at improving health care delivery and testing new treatment options for patients with asthma and Chronic Obstructive Pulmonary Disease (COPD). The group includes investigators in the NHLBI AsthmaNet program (http://asthmanetresearch.org/), NHLBI Pulmonary Trials Collaborative (PTC; http://www.pulmonarytrials.org/ and the American Lung Association Airways Clinical Research Centers (ALA-ACRC; http://cctrials.org/alaacrc/). Our mission is to provide those with lung disease access to cutting edge research and education to better manage their condition. Along with the University of Illinois Health System, the BCC promotes healthier communities for a healthier city.
Irena Levitan, PhD (Vascular Diseases, Biophysics, Biomechanics)
Research in Dr. Levitan’s lab focuses on the impact of dyslipidemia and oxidized lipids on endothelial dysfunction. Their primary objective is to determine how lipid environment controls endothelial ion channels and cellular biomechanics. Her group provided multiple structural and mechanistic insights into the role of cholesterol in regulation of ion channels and demonstrated the critical role of endothelial K+ channels in endothelial responses to mechanical forces. Most recently, her group demonstrated that endothelial Kir channels are essential for flow-induced release of nitric oxide, a major vasoactive anti-inflammatory agent. She also studies the roles of bacterial toxins on K+ channel function and the role of these channels in inflammation. Dr Levitan has also discovered that plasma dyslipidemia induces endothelial stiffening and increase in endothelial force generation, an effect that is associated with disregulated angiogenesis. Currently, her group is investigating the mechanisms of oxLDL-induced endothelial stiffening and its implications for angiogenesis. They also investigate the cross-talk between oxidized lipids and matrix stiffness in the regulation of angiogenesis in lung fibrosis.
Viswanathan Natarajan, PhD (Vascular Diseases, ALI/ARDS, Pulmonary Fibrosis, Lung Inflammation, Lung Cancer)
Dr. Natarajan is a basic/translational research scientist and the overall goal of his research is to understand molecular mechanisms and signaling pathways that mediate lung inflammation and injury and develop novel therapeutic agents to ameliorate pulmonary leak, lung edema, and restore barrier integrity. Three major areas of focus are: (i) mechanisms of ROS production and role of ROS regulation of pro-inflammatory genes in lung disorders, (ii) Sphingolipids in lung pathologies and intracellular S1P as a co-epigenetic regulator of lung inflammation and injury, and (iii) Role of cardiolipin (CL) and CL remodeling enzyme, lysocardiolipin acyltransferase in development, progression and metastasis of non-small cell lung cancer. The underlying premise is that understanding basis of altered chromatin remodeling by ROS and S1P in different lung pathologies will help to identify signaling targets and develop new pharmacological approaches to restore lung function and integrity. Recently, his group has initiated new and exciting studies on S1P as a co-epigenetic regulator of chromatin remodeling and expression of pro-inflammatory genes in sepsis- and bacteria-mediated lung inflammation and injury. Their preliminary data show that in sepsis-induced lung injury, S1P generated by SphK1 regulated chromatin remodeling, while with infection of Pseudomonas aeruginosa in the mouse lung, nuclear SphK2 played an important role in H3 and H4 histone acetylation and chromatin remodeling. These data suggest an intriguing role for S1P as a co-epigenetic regulator of cell functions. Dr Natarajan has been continuously funded by NIH/HLBI since 1993 to work on mechanisms of lung vascular permeability.
Sharmilee Nyenhuis, MD (Asthma, Clinical Outcomes)
Dr. Nyenhuis’ previous and ongoing research is committed to addressing health disparities in asthma. Working with both basic and clinical scientists she has addressed health disparities across the research spectrum from evaluating mechanisms of poor asthma control in older adults and African American adults with asthma to community-based research in African Americans adults and children with asthma. She currently is funded by PCORI to evaluate home-based interventions to improve asthma morbidity in minority children with asthma and is the asthma co-chair for PCORI’s clinical data research network, CAPriCORN. She was recently awarded a K01 funded by the NHLBI to develop and test a community-based walking intervention specific for African American women with asthma. Her passion in asthma health disparities extends beyond her research as she is a past-president and an active member of the Chicago Asthma Consortium, a coalition of medical and public health professionals, business leaders, government agencies, community-based organizations, and individuals dedicated to improving the quality of life for people with asthma through advocacy, education and collaboration.
Gye Young Park, MD (Lung Inflammation, ARDS, Asthma)
Gye Young Park is interested in the role of macrophages in lung diseases, including ARDS and asthma. His approach uses a translational research strategy, beginning with cellular molecular research, extending to mouse animal models and eventually to patient based clinical studies. His research focuses on the regulation of expression of macrophage phenotype-specific genes at multiple levels, from nucleosomal and transcriptional to translational regulation. The tools used in his research are micro-RNAs, nucleosomal modifications and multiple transcriptional factors including NF-kB, PU.1 and CEBP-b. As a disease animal model, He uses a triple allergen-induced acute/chronic asthma model and LPS induced ARDS model. Dr Park has an IRB approved bronchoscopic sub-segmental allergen challenge program for patients with mild intermittent asthma.
Bharati Prasad, MD (Sleep disordered breathing, Health Disparities)
Dr. Prasad’s two major research interests are evaluating the heterogeneity in cardiovascular response to positive airway pressure treatment in sleep apnea and health disparities in sleep disorders. Her current research examines sleep related quantitative differences between hypertension responders and non-responders to positive airway pressure treatment in patients with sleep apnea. This program aims to identify factors that distinguish individuals or populations that are most likely to derive cardiovascular health benefits from positive airway pressure treatment. She is also interested in sleep health disparities in vulnerable populations. The goal of this program is develop and test tailored interventions through comparative effectiveness research to reduce sleep health disparities.
Israel Rubinstein, MD (Drug Delivery, Discovery and Entrepreneurial Activities)
Dr. Rubinstein’s research program unravels the mechanisms underlying successful resuscitation by an FDA-approved lipid emulsion (IntralipidR) of certain accidental and intentional drug- and xenobiotic-induced lethal overdoses/poisonings, such as cocaine, and by brodifacoum, a ‘superwarfarin’ used as a weapon of mass destruction. His research group has discovered that FDA-approved IntralipidR and cholestyramine (QuestranR)are safe and efficacious antidotes of local anesthetics and brodifacoum poisonings, respectively. As a result of these discoveries, Dr Rubinstein has co-founded two pharmaceutical start-up companies in Chicago to commercialize both products through the Animal Rule and Orphan Indication regulatory pathways. One company, ResQ Pharma, Inc., has already submitted an investigational new drug (IND) application to the FDA. Dr. Rubinstein is Board Member and Director of Advanced Life Sciences, a publicly-traded biopharmaceutical company in Woodridge, Illinois, USA. Dr. Rubinstein has authored more than 200 peer-reviewed scientific papers and has several issued and pending patents. He is Editor-in-Chief, Nanotechnology, Science and Applications, Clinical AND REVIEW Editor, Nanomedicine: Nanotechnology, Biology and Medicine and Associate Editor, International Journal of Nanomedicine.
Sunit Singla, MD (Vascular Biology, ALI/ARDS, Pulmonary Hypertension)
Dr. Singla’s long term goal is to lead a program of research that contributes towards maintaining a pipeline of novel therapeutic strategies targeting inflammation and vascular leak during lung diseases such as ARDS. The primary focus of his recent work is on the role of the tumor suppressor gene, WWOX, in mediating these features of ARDS. Utilizing a variety of experimental methods in both cellular and animal models, his work aims to elucidate precise molecular mechanisms of ARDS disease pathogenesis, and to conceptually establish therapeutic strategies based on this knowledge.