The Brown Respiratory Research Training Program (T32 HL134625 01) has as its overall objective the training of physicians and scientists to become independent investigators in the pathobiology of respiratory diseases and in the health services, outcomes, and epidemiology of these diseases. The Program aims to bridge gaps between biomedical, behavioral and public health disciplines to advance knowledge regarding how best to reduce disease burden among patients with diseases that affect the respiratory system. Interested fellows would apply toward the end of their 3 year training program and if accepted, would receive funding support for further years of training as junior faculty in the division.

Brown Respiratory Research Training Program

Our division has a long history of research into the causes and treatment of sepsis. Dr. Mitchell Levy has been a leader in the creation of international professional organization-based sepsis guidelines for over 20 years and the co-director of the Ocean State Clinical Coordinating Center, which manages large, multi-center international RCTs in sepsis. There is significant expertise in the division around developing protocols for large sepsis RCTs. We have also been involved in national and State-wide initiatives in sepsis performance improvement programs and are major contributors to the national SEP-1 mandated reporting with sepsis measures.

Mitchell Levy MD is conducting work on performance improvement techniques and has been working with The Surviving Sepsis Campaign to improve the survival of sepsis. He has conducted several trials, testing the impact of these “sepsis bundles” and a multiple-faceted intervention in facilitating knowledge transfer. He was recently awarded a grant from the National Heart Lung and Blood Institute (NHLBI) from the National Institutes of Health (NIH) for a type 2 Hybrid effectiveness-implementation trial, involving a cluster randomized controlled trial of 18 hospitals, to test the efficacy of the Hour-1 bundle vs the 3-hour bundle for the treat of sepsis and septic shock. This grant and study is entitled, Assessment of Implementation Methods in Sepsis (AIMS study). The grant is for 5 years. His work with the New York State Sepsis Initiative was published (2017 and 2018) in the New England Journal of Medicine and the American Journal of Respiratory and Critical Care Medicine. A study on racial disparities from the New York State database was published (2019) in Health Affairs. He continues to access the 150,000 patient NYS DOH database to work with fellows and other collaborators on further manuscripts. This includes: 1) Impact of sepsis bundles on patients with chronic kidney disease and congestive heart failure, 2) Development of sepsis phenotypes from clinical data, and 3) Readmission rates and unintended consequences of sepsis performance measures.

Rhode Island Hospital is an Extracorporeal Life Support Organization (ELSO) Center of Excellence. Corey Ventetuolo, MD, MS is the Medical Director of the Adult Extracorporeal Life Support Program and Adeel Abbasi, MD, ScM is the Associate Medical Director. The research mission of the ECLS service includes participation in registries (ELSO, International Research Database For Extracorporeal Support (INDEX)), and biorepositories, collaboration with the Artificial Intelligence Laboratory at the Brown Center for Biomedical Informatics to apply machine learning algorithms to predict outcomes in ECLS (Adeel Abbasi, MD, ScM/T32 graduate), translational studies of novel biomarkers, and work in best practice for anticoagulation monitoring modalities.

The Pulmonary Hypertension Center (PHC) was established in 1991 and has been under the leadership of Dr. James Klinger since 2001 also includes Drs. Corey Ventetuolo (Associate Chief), Christopher Mullin, MD, MHS (Associate Director), Mary Whittenhall, MSN, APRN, AGACNP (Center Coordinator) and Navneet Singh, MD (T32 graduate). The PHC was the first center in New England to be accredited as a Center of Comprehensive Care by the Pulmonary Hypertension Association. The Center participates in numerous clinical trials of new and approved therapies for the treatment of pulmonary arterial hypertension (PAH) and is currently enrolling patients in several NIH- and industry-funded clinical trials. The PHC also regularly enrolls patients in several registries.

Dr. Klinger’s research is concentrated on the pathobiology of pulmonary vascular remodeling in pulmonary hypertension and pulmonary vascular endothelial barrier function. In collaboration with Drs. Peter Quesenberry and Olin Liang at the Rhode Island Center for Stem Cell Biology, Dr. Klinger has been investigating the role of mesenchymal stem cell extracellular vesicles and bone marrow-derived progenitor cells in the pathogenesis and treatment of pulmonary hypertension. Dr. Klinger’s interests also include several newly identified transcription factors that have recently been implicated in pulmonary vascular disease. Dr. Klinger’s other research interests include the natriuretic peptides, nitric oxide and downstream signaling mechanisms that are regulated by cGMP and cGMP-dependent protein kinase. His interest in these pathways is related to their role in modulating pulmonary hypertensive and right ventricular hypertrophic responses, as well as pulmonary endothelial barrier function.

Dr. Ventetuolo’s research includes both clinical and translational studies focused on the genetic and molecular mechanisms of sex hormone signaling and metabolism as a means for understanding sexual dimorphism in PAH and right ventricular function in health and disease. She has served as study co-chair for an NIH-funded clinical trial of anastrozole in PAH and is the Principal Investigator of the EDIPHY Study, the first NIH-funded clinical trial of a naturally occurring hormone, dehydroepiandrosterone, in PAH. She has developed a novel method to endotype patients with pulmonary vascular disease using “liquid biopsies” from pulmonary artery endothelial cells during routine right heart catheterizations and along with collaborator Elizabeth Harrington is developing this method for therapeutic screening and to identify novel mechanistic paradigms in pulmonary arterial hypertension. Active collaborations also include quality of life research with Kate Guthrie, PhD in the Center for Behavioral and Preventative Medicine at Brown.
Dr. Mullin’s research is focused on PAH related to systemic sclerosis (SSc) and other forms of connective tissue disease (CTD) as well as chronic thromboembolic pulmonary hypertension (CTEPH). He has ongoing clinical research projects examining and predicting outcomes and hospitalizations in SSc-PAH and CTD-PAH. He has interest and expertise in the use of pulmonary vascular responses to exercise (measurement of cardiopulmonary hemodynamics with exercise during right heart catheterization) to identify early pulmonary vascular disease in SSc and other patient populations at-risk for PAH.
Dr. Navneet Singh is studying the role of the liver as an inflammatory and metabolic mediator in pulmonary vascular disease. His work includes experimental models of pulmonary hypertension as well as translational studies in patients with PAH.

The Vascular Research Laboratory (VRL) is a multidisciplinary group of investigators studying the pulmonary circulation and cardiopulmonary interactions using cells, animal models, clinical studies, and epidemiology studies using database approaches. Faculty include MD’s, PhD’s, pulmonary/critical care and cardiology specialists. Research is multidisciplinary with a focus on diseases resulting in pulmonary edema, pulmonary hypertension, and cardiac complications of pulmonary hypertension. The VRL faculty cumulatively have over $2.3 million in direct costs per year of funding to support their research. In addition, the VRL is the site of the Cardio Pulmonary Vascular Biology Center for Biomedical Research Excellence (CPVB COBRE) with has $1.5 million in direct costs per year.
Websites: www.brown.edu/Research/Vascular_Research_Laboratory; www.cpvb.org

Gaurav Choudhary, MD, is Chief of Staff for Research at the PVAMC. The focus of research in his laboratory is to evaluate the mechanisms underlying exercise intolerance, vascular dysfunction and cardiac dysfunction seen in pulmonary vascular diseases. The laboratory uses a variety of in vitro, ex vivo and in vivo approaches utilizing the preclinical models of pulmonary hypertension and emphysema. His NIH-funded research is focused on mechanisms of right ventricular fibrosis in pulmonary hypertension. He also performs epidemiological (using VA and non-VA data) and clinical studies in area of pulmonary hypertension and right heart function. He is site PI with Jankowich on a VA-funded Merit Review grant to study the effects of tadalafil on pulmonary hypertension associated with COPD, lung vascular remodeling, and RV dysfunction. Dr. Choudhary is funded by an RO1 and collaborates with Drs. Clements, Jankowich, Harrington, Lu, Rounds, and Wu.

Richard Clements, PhD, is expert in microvascular injury in diabetes and in mitochondrial function and collaborates with Choudhary.

Elizabeth Harrington, PhD, is PI on the Brown Respiratory Research T32 Training Program. Dr. Harrington is PI or co-PI on three training grants that support undergraduate, medical student, and graduate student research. The focus of her research is characterization of intracellular signaling mechanisms regulating endothelial cell functions and/or responses to environmental cues. Current investigations include elucidation of the molecular mechanism by which NRP and Rab GTPases regulate endothelial monolayer permeability and apoptosis and elucidation of signaling pathways which are differentially activated in pulmonary and systemic microvascular endothelial cells in response to oxidative stress.

Matthew Jankowich, MD, studies conditions predisposing to pulmonary hypertension and RV failure with a focus on non-PAH PH, and also studies the interactions between systemic vascular disease and pulmonary vascular disease. He has been conducting epidemiologic research with cardiologists Gaurav Choudhary, M.D. and Wen-Chih Wu, M.D. using data from the Jackson Heart Study (JHS), the largest prospective observational study of cardiovascular disease in African-Americans. Brown University is a Vanguard data center for the JHS. Dr. Jankowich is a site investigator for the Tadalafil for Pulmonary Hypertension Associated with Chronic Lung Disease (TADA-PHiLD) multicenter randomized double-blind placebo-controlled clinical trial (co-PI Dr. Sharon Rounds). He is also a site investigator for the OPTIMAL-HF study (PI: Dan Gottlieb, M.D., Boston VAMC), a randomized parallel group study comparing CPAP, oxygen, or optimized medical therapy for patients with sleep apnea and chronic heart failure with a reduced ejection fraction.

Sharon Rounds, MD, is interested in mechanisms of lung vascular injury in conditions causing pulmonary hypertension and acute lung injury. Her work focuses on mechanisms of cigarette smoke exposure on the pulmonary circulation. Dr. Rounds is Contact PI and lead investigator on a VA Merit Review for a multi-center trial to study the effects of PDE5 inhibitor, tadalafil, on shortness of breath in Veterans with COPD complicated by pulmonary hypertension. She is also PI of Advance RI-CTR, a $20 million, 5-year grant to develop research infrastructure in the state of Rhode Island. She collaborates with Drs. Choudhary, Harrington, and Jankowich.

Other Research areas through the VAMC include…

Wen-Chih (“Hank”) Wu, MD, MPH, is an Investigator in the Center of Innovation in Long-Term Services and Supports for Vulnerable Veterans (COIN) at the PVAMC. Dr. Wu studies the relationship between anemia, blood transfusion and death in elderly patients undergoing non-cardiac surgery and delivery of care to patients with CHF. In collaboration with Drs. Choudhary and Jankowich, he also studies factors predisposing to pulmonary hypertension and RV failure. He is funded by VA Merit Review grants. He mentors in the areas of epidemiology and outcomes of pulmonary hypertension and CHF.

Linda Nici, MD (Section Chief) is conducting work on interventions to improve patient- centered outcomes in COPD. Through the Pulmonary Rehabilitation Program as well as the Pulmonary Risk Reduction Initiative, COPD patients at risk for hospital admission or readmission are receiving additional health provider support through education initiatives, promotion of exercise, and identification of risk factors that can be modified to prevent hospitalizations. Studies have included: 1) Rates and predictors of hospital readmission among patients with COPD in the Department of Veterans Affairs using the national VINCI database; 2) The trajectory of physical activity following pulmonary rehabilitation; 3) Physician-led education interventions designed to prevent readmission after COPD exacerbation. In addition, the VA has a robust lung cancer screening program which includes a patient registry of all positive screens. This has allowed for evaluation of interventions for positive screens as well as survival data for veterans with lung cancer.

Eric Gartman, MD has research interests in airway disease, diaphragmatic dysfunction and exercise limitation. He is currently the principle investigator for a study evaluating the use of Cardiopulmonary Exercise Testing (CPET) in predicting outcomes after cancer diagnosis and treatment, as well as a collaborator in other clinical research studies using CPET as an outcome measure. He is a site co-investigator in the OPTIMAL-HF study above.

Lung Cancer Screening Program: The Providence VAMC implemented a clinical lung cancer screening program using LDCT starting in December 2013. We are currently evaluating the utility of lung cancer screening in the first years of implementation in terms of: rates of nodule detection and workup; prevalence of lung cancer at initial screening; sensitivity and specificity of lung cancer screening at the Providence VAMC; and outcomes of lung cancer diagnosis in the screened population compared to the pre-screening population.

Mitchell Levy MD and Corey Ventetuolo MD, MS are amassing a database for all patients admitted to the Medical Intensive Care Unit with sepsis, ARDS and those requiring extracorporeal life support. Blood is being collected for Proteomic and Genomic evaluation, and we have multiple research projects (collaborating with fellows and faculty from other departments) utilizing samples from this database.

Mitchell Levy MD is examining large data sets of severely septic patients (Centers for Medicare and Medicaid services) to determine the viability of a disease-specific risk-adjusted mortality model in patients with severe sepsis and septic shock. Using recursive partitioning and regression analysis, statistical correlations with these features are being identified. The aim is to generate a predictive model incorporating these factors to identify mortality risk. These efforts are in collaboration with Stan Lemeshow and Gary Phillips, from Ohio State University School of Biostatistics.

Nicholas Ward, MD is currently working two studies of ICU utilization and practice. The first focuses on informed consent in ICUs and is part of multi-center study looking at this issue based out of Brown, the University of Chicago, and Beth Israel Deaconess Hospital. The second project is a quantitative and qualitative analysis of ICU admissions for non-critically ill patients using a data base created at Rhode Island hospital. This project is being done in conjunction with Dr. Jason Aliotta.

Jason Aliotta, MD is involved in several quality improvement projects that focus on ICU utilization and physician workflow and staffing at Rhode Island Hospital Medical ICU. In addition, he is the principal investigator in a funded randomized control trial that evaluates the utilization and effectiveness of breath-actuated nebulizers compared with standard nebulizers in patients admitted with acute COPD exacerbations.

Our division has been involved in multiple research projects for improving end of life care in the critically ill and improving communication for caregivers during end of life conversations. Dr. Nicholas Ward has a special interest in ethics and has also led several initiatives for physician/patient ratios in the ICU and well as decision-making during the COVID-19 pandemic. Mitchell Levy MD is continuing his work in end-of-life care. Over the past years, he has published numerous manuscripts in the field, including one on the visiting hours in the MICU, as well as several opinion pieces, describing the barriers to adequate end-of-life decision-making. Dr. Levy has completed a state-wide initiative on communication bundles in the ICU (with a research fellow as lead author) the results of which have been published in Critical Care Medicine.

Led by Dr. Christopher Mullin and in conjunction with interventional radiology, emergency medicine, cardiothoracic surgery and cardiology, the Pulmonary Division has developed and plays an integral role in the Pulmonary Embolism Response Team (PERT) that evaluates all cases of pulmonary embolism (PE) admitted to Lifespan hospitals. Dr. Mullin also oversees a Post-PE Clinic as part of the PHC which includes an active population of patients with CTEPH.

The Brown Medicine-Rhode Island Hospital Interstitial Lung Disease (ILD) Center was established in 2014 to provide comprehensive care to those afflicted by these complex and often life-threatening diseases and is now led by Dr. Doug Martin. The Brown-RIH ILD Center has grown steadily and includes active research, educational and community support programs to compliment a multidisciplinary approach to patient care. In 2018 it was selected as a member of the Pulmonary Fibrosis Foundation (PFF) Care Center Network.

E. Jane Carter, MD, has a primary interest in Tuberculosis- both domestically and internationally. Dr. Carter is the co-director of the HIV-TB Scientific Working Group of the Providence Boston Center for AIDS Research (CFAR). Dr. Carter has headed the Brown Kenya Program medical exchange program for 20 years which also contains a broad scope of research projects and opportunities. Her most recent research project has focused on pediatric TB diagnosis and treatment in high burden, resource poor countries, such as Kenya. She is also a co-founder of the Pulmonary Critical Care Training Program at Black Lion Hospital in Addis Abba, Ethiopia.

Richard P. Millman MD. The relationship between obstructive sleep apnea and chronic renal disease is being pursued with a large grant to Brown from an anonymous donor. This study is trying to determine the relationship between stage 4 chronic renal disease, sleep disordered breathing, 24-hour blood pressure measurements and markers of potential cardiac disease. This is being done in conjunction with the Division of Renal and Hypertension in the Department of Medicine

Katherine Sharkey MD, PhD studies the interplay between mood regulation, circadian rhythms, and sleep. Sharkey leads a multi-site randomized controlled trial funded by an R01 from NIMH that tests a chronotherapy intervention for treatment of perinatal depression with colleagues from Northwell Health and the University of North Carolina-Chapel Hill. In addition, she was recently awarded a Women’s Health Administrative Supplement from NIGMS to adapt and refine a video and app-based sleep intervention tailored to perinatal women to be delivered by direct care workers to their pregnant and postpartum clients. Her other projects include a study of maternal sleep patterns, perinatal weight gain and infant feeding in Latinx families in collaboration with colleagues from the School of Public Health. Sharkey’s lab examines multiple factors associated with circadian rhythms and mood regulation, including wrist actigraphy, ambulatory EEG monitoring, measures of hyperarousal, cognitive processing, hormone levels, biomarkers, and infant behaviors. Dr. Sharkey’s other scholarly interests include sleep disorders and women’s health and advancement and leadership among women in academic medicine.

Ghada Bourjeily, MD. Dr. Bourjeily’s research focuses on sleep in women, particularly in pregnancy. She has led multiple studies funded by the NIH examining sleep disordered breathing, and its impact on perinatal outcomes-mainly cardiovascular and metabolic outcomes and fetal growth-, as well as ways to predict the new onset development of sleep disordered breathing in this population, and examine factors impacting adherence to therapy in this population. She is currently funded to examine deep machine learning in sleep disordered breathing and will soon launch a new study aimed at examining the interplay between sleep, nutrition, and race in pregnancy. Dr. Bourjeily is a founding member of the Brown University Maternal and Perinatal Sleep Scientists (BUMPSS) team with expertise in sleep (Sharkey and Bourjeily), epidemiology, nutrition, mental health, and obstetrics and the team is collaborating on studies examining sleep and nutrition in pregnancy.

Dr. Bourjeily’s other interests include mindfulness training and its impact on lung health and perinatal outcomes. In collaboration with researchers at UMASS, she served as site PI on a two site NCCIH study that examined the impact of mindfulness training on asthma control and is currently a Co-I on an NHLBI trial investigating mechanistic pathways of mindfulness training on cardiovascular perinatal outcomes. Dr. Bourjeily serves as a senior faculty advisor with Dr. Rounds for the advance K-scholars program of the advance CTR.