PH Research at a Glance
Elena Goncharova, PhD
Proliferative/metabolic signaling in PH; smooth muscle pathobiology
Patrick Pagano, PhD
NADPH oxidase signaling and oxidative stress in PAH
Adam Straub, PhD
NO, redox signaling, vessel myography in PAH
Imad al Ghouleh, PhD
Molecular biology of RV failure
Cindy St. Hilaire, PhD
Human genetics and pulmonary vascular calcification
Sruti Shiva, PhD
Platelet mitochondria in PAH
Ana Mora, MD
Mitochondria and aging in PAH
Prithu Sundd, PhD
In vivo imaging and role of platelet activation in PAH
Partha Dutta, DVM, PhD
Myeloid and stem cell control of inflammation in PAH
Mark Gladwin, MD
NO, nitrite, PH, metabolic syndrome and HFpEF
Stephen Chan, MD, PhD
Systems biology, non-coding RNAs in PH
Marc Simon, MD, MS
RV mechanics, nitrite in PH
Alison Morris, MD, MS
HIV-associated PAH
Michael Mathier, MD
Multi-center PH trials
Belinda Rivera-Lebron, MD
Acute PE and CTEPH, portopulmonary PH
Michael Risbano, MD
PAH biomarkers, pulmonary vasodilation, exercise in PH
Mauricio Rojas, MD
Ex vivo human lung physiology in PAH
PH Laboratories
Chan Lab
Dr. Chan’s lab studies the molecular mechanisms of pulmonary vascular disease and pulmonary hypertension (PH). Ongoing projects include: 1) Defining the network biology of non-coding RNAs in pulmonary hypertension, 2) Studying the molecular regulation of mitochondrial metabolism by microRNAs, and 3) Defining the regulation of circulating microRNAs in hypoxia and exercise. Dr. Chan’s Lab
Goncharova Lab
Dr. Goncharova’s research interests have focused on the signaling mechanisms regulating cellular energy metabolism, proliferation, motility and survival as it relates to the pathogenesis of pulmonary arterial hypertension (PAH) . Her current work specifically focuses on the roles of HIPPO and mTOR signaling networks in pulmonary vascular remodeling and in identifying novel molecular targets and therapeutic options to reverse established PAH.
Pagano Lab
The overall goal of our laboratory is to investigate the role of NADPH oxidase in normal cellular function as well as under a variety of pathophysiological conditions. We are currently developing isoform-specific inhibitors to delineate the contribution of specific NADPH oxidase isoforms in elevated reactive oxygen species (ROS) production in various cardiovascular diseases (CVDs). We are also employing conventional and cutting-edge technologies such as immuno-spin trapping, mass spectroscopy and proteomics to investigate the mechanisms mediating the effect of adventitia-derived hydrogen peroxide (H2O2) as a paracrine mediator of vascular dysfunction in CVD. Dr. Pagano’s Lab
St Hilaire Lab
Dr. St. Hilaire’s research aims to characterize novel mechanisms regulating vascular calcification and vessel remodeling, and incorporates cell biology, signal transduction, and in vivo models. Particular research angles include the role of mechanical stress, extracellular matrix remodeling, and cellular stress response, in a variety of vascular disease contexts. Dr. St. Hilaire’s Lab
Sundd Lab
The Sundd lab aspires to elucidate the molecular and biophysical mechanism of leukocyte-platelet-endothelium interaction during inflammation and how these events contribute to Vaso-Occlusive Crisis (VOC) and ACS in SCD. To achieve this we are using a multi-scale integrative physiologic approach, which involves in vivo Multi-Photon Excitation (MPE) fluorescence microscopy in transgenic and knock-in mice, microfluidic assays with patient blood, total internal reflection fluorescence (TIRF) microscopy, structured illumination microscopy (SIM), laser confocal microscopy, electron microscopy and various biochemical approaches. This multi-scale approach enables us to address the link between the pathophysiology of ACS affecting the lung (macro-level response) to the aberrant cellular events (micro-level response) driving the vaso-occlusion and the molecular interactions (nano-level response) enabling those cellular events. Identifying the molecular mechanism of vaso-occlusion in the lung will inspire therapeutics to prevent ACS in SCD patients. Dr. Sundd’s Lab
Simon Lab
Dr. Simon’s current research interests include the study of right ventricular structural and functional adaptation to pressure overload in pulmonary hypertension and heart failure. Dr. Simon’s labs focus on 1) advanced analysis of clinical hemodynamics and 2) right ventricular myocardial biaxial biomechanics. He is also interested in outcomes research in end-stage heart failure patients treated with implantable devices. His recent projects include assessment of right ventricular-pulmonary arterial coupling in pulmonary hypertension patients and its relation to outcomes, and right ventricular strain analysis by echocardiographic speckle tracking to screen HIV patients for right ventricular dysfunction.
Dr. Risbano's research
Dr. Risbano is interested in the hemodynamic evaluation of subjects with pulmonary hypertension and correlation of hemodynamic values with biomarkers for the early diagnosis of pulmonary hypertension. Dr. Risbano is directly involved in the clinical and research exercise right heart catheterization efforts in which we identify patients with various forms of exercise pulmonary hypertension.
He has worked closely with Dr. Mark Gladwin in the study of endothelial function in response to the infusion of aged red cells. Most recently he has published the study Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function in the American Journal of Respiratory and Critical Care Medicine. This study demonstrated that intra-arterially infused red blood cells at the upper limits of storage impaired endothelial function, as measured by the reduced forearm blood flow responses to acetylcholine, an endothelium NO synthase-dependent vasodilator.
Dr. Risbano is also the PI for a number of investigator initiated and Pharma related research clinical trials.
Morris Lab
Dr. Morris’ research interests include HIV-associated lung disease as well as the role of the microbiome in disease. Her group works with large cohort epidemiologic studies of HIV and other diseases as well as in translational studies in which physiologic and molecular techniques are applied to patient populations. As part of her role in the Center for Medicine and the Microbiome, she works with collaborators in diverse areas studying the microbiome.
Dr. Morris’ research interests focus in several overlapping areas:
1. Role of the microbiome in HIV-associated lung disease
2. Understanding and manipulating the respiratory and gut microbiota in the ICU
3. The role of nitrate-reducing bacteria in pulmonary hypertension
2. HIV-associated emphysema and pulmonary hypertension
3. Role of Pneumocystis and other fungi in COPD and HIV
Gladwin Lab
PI: Mark Gladwin, MD
Dr. Gladwin’s clinical research and expertise focuses on pulmonary hypertension and pulmonary complications of sickle cell disease. Since 1998, Dr. Gladwin’s research has led to four scientific discoveries: 1) the nitrite anion is a circulating storage pool for NO bioactivity that regulates hypoxic vasodilation and the cellular resilience to low oxygen and ischemia; 2) a novel physiological function for hemoglobin as an electronically- and allosterically-regulated nitrite reductase; 3) the characterization of a novel mechanism of disease, hemolysis-associated endothelial dysfunction; and 4) the mechanistic, clinical, and epidemiological description of a human disease syndrome, hemolysis-associated pulmonary hypertension.
Straub Lab
PI: Adam Straub, PhD
The Straub laboratory investigates redox-controlled cell signaling mechanisms that regulate endothelial and smooth muscle biology of the microcirculation in the setting of both physiology and cardiovascular disease. Dr. Straub’s Lab
Shiva Lab
PI: Sruti Shiva, PhD
Dr. Shiva’s research focuses broadly on understanding the mechanisms by which mitochondrial function is regulated, particularly by reactive oxygen and nitrogen species and the contribution of these mechanisms to cardiovascular health and disease pathogenesis. Using a wide spectrum of techniques ranging from the biochemical study of isolated mitochondria to whole animal models and measurement of bioenergetic function in human blood cells, the Shiva lab is currently engaged in a number of active projects along four major scientific themes:
- Utilization of platelets to measure human mitochondrial function in health and disease.
- The role of platelet mitochondria in hemolytic disease pathogenesis.
- The mitochondrion as a physiological target for nitrite.
- Myoglobin as a regulator of mitochondrial function.
Mora Lab
PI: Ana Mora, MD
Dr. Mora’s research is focused in the understanding of the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) and pulmonary arterial hypertension (PAH). Because aging a major risk factor for IPF, she studies the role of mitochondria dysfunction and altered proteostasis in the aging lung epithelial cell in the activation of pro-fibrotic responses. She has found that mitochondrial quality control has a critical role in the genesis of aging related susceptibility to lung fibrosis. Her research is aimed to identify novel diagnostic and therapeutic mitochondrial targets to control lung fibrosis. In parallel, her laboratory analyzes the role of mitochondrial homeostasis in vascular remodeling and the pathogenesis of PAH. Dr. Mora’s Lab
Dutta Lab
Cardiovascular disease is the leading cause of death in developed countries. Inflammation aggravates outcome of cardiovascular disease including atherosclerosis and infarct healing after myocardial infarction (MI). During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons.
Another area of my research interest is fate and differentiation of hematopoietic stem and progenitor cells in cardiovascular disease. Hematopoietic stem cells get activated after acute or chronic inflammation and give rise to exaggerated myelopoiesis. However, most hematopoietic stem cells (HSC) are quiescent, and it is currently unknown whether they respond to ischemic organ injury. We identified a CCR2+ HSC subset, which has fourfold higher proliferative rate than CCR2- HSC, as the most upstream contributor to myelopoiesis after myocardial infarction. CCR2+ HSC display bias towards the myeloid lineage and dominate the migratory HSC population after myocardial infarction and in steady-state. These data shed new light on the regulation of emergency hematopoiesis after ischemic injury and identify novel therapeutic targets to modulate leukocyte output after myocardial infarction.
Al Ghouleh Lab
Dr. Al Ghouleh’s lab is focused on the study of pulmonary hypertension, a devastating disease that currently has no treatment. An area of major focus is defining the mechanisms that underlie right ventricular phenotypic changes in this disease. As the disease progresses, extensive remodeling occurs in the blood vessels that compose the pulmonary circulation which leads to progressive increases in pulmonary vascular resistance. This in turn causes pressure overload on the right ventricle (RV) of the heart which undergoes remodeling as a result. Initially, RV remodeling is adaptive, but eventually becomes maladaptive and leads to RV failure. There is very little known about the pathways that drive this process. Dr. Al Ghouleh’s lab is focused on understanding these pathways. Their preliminary findings identified a signaling cascade involving the protein ERM binding phosphoprotein 50 (EBP50), also called NHE regulatory factor 1 (NHERF1), in this process. Current research is designed to test this pathway in the RV following pressure overload challenge and to delineate upstream and downstream molecules involved with a long-term focus on translating mechanistic insights into potential therapeutic strategies aimed at the RV.
Rojas Lab
Dr. Rojas’ basic research is on the biology of lung injury and repair, especially in models of pulmonary fibrosis, acute lung injury and radiation. Dr. Rojas’ laboratory has produced pioneer work on the development of pre-clinical models for the use of bone marrow derived-MSC on acute and chronic injury. His novel area of research is the human ex vivo perfusion program, using human normal lungs and diseased lungs, studying the effect of novel therapies like stem cells, non-coding RNAs, small molecules as pre-clinical models for the implementation of new therapies for lung diseases. This protocol in combination of the collection of tissues samples from explanted lungs, has allowed his laboratory to build a program of organ/tissue collection from normal and disease lungs including scleroderma.