Basic Research Activities
Alpha Fowler, MD
Dr. Fowler's research is focused on vascular inflammation
as it relates to the development and progression of various
disease conditions. Several different aspects of the inflammatory
process are currently under investigation. Dr. Fowler and
his colleagues are studying the role of nitric oxide (NO)
in the regulation of endothelial Interleukin-8 (IL-8) production.
Work from Dr. Fowler's laboratory showed that inhaled NO
gas dramatically attenuated acute pulmonary vascular inflammation
and subsequent injury resulting from bacterial sepsis in
an animal model of lung injury. More recently, his laboratory
has demonstrated that NO exerts a dual regulatory effect
on vascular endothelial IL-8 expression depending upon the
activation state of the endothelial cells. Furthermore,
this effect is mediated by the transcription factor NF-kB.
Currently the signaling pathways (e.g., c-jun NH2-terminal
kinase) involved in NO-mediated attenuation of IL-8 expression
are under investigation. Dr. Fowler's research is supported
by the National Institutes of Health. Dr. Fowler collaborates
with other university investigators interested in this area.
Marjolein de Wit, MD, MS
Dr. de Wit's area of research is focused on outcomes research of critically
ill patients undergoing invasive mechanical ventilation. Specifically, her
areas of research focus on (1) sedation strategies that aim to decrease the
duration of mechanical ventilation, (2) the impact of alcohol and other
drug use disorders on development and progression of critical illness, and
(3) relationship between patient-ventilator asynchrony and mechanical
ventilation duration.
Shobha Ghosh, PhD
Dr. Ghosh's research interest is in cholesteryl ester metabolism in atherosclerosis; regulation of cholesteryl ester hydrolase; role of HDL in regulating cholesterol efflux from lipid laden macrophage foam cells; role of inflammation and lipid mediators in cardiovascular disease.
Coronary heart disease is a leading cause of death in the United States. Atherosclerosis or deposition of cholesterol ester-rich macrophage foam cells in arterial walls is the underlying mechanism. Dr. Ghosh's lab has identified and cloned the rate limiting enzyme cholesteryl ester hydrolase (CEH) from human macrophage foam cells. CEH catalyzes the hydrolysis of intracellular cholesterol esters making free cholesterol available for HDL-mediated removal and thus plays a crucial role in preventing cholesteryl ester deposition in peripheral tissue including the artery wall associated macrophage foam cells that are central to the formation of atherosclerotic plaques. Dr. Ghosh's lab has demonstrated a rapid and significant mobilization of intracellular cholesterol ester by over-expression of CEH. Macrophage-specific transgenic expression of CEH leads to an attenuation of high-fat high-cholesterol diet-induced atherosclerosis and lesion necrosis in LDLR-/- mice. Pathways regulating this enzyme are under study and how these pathways can be modulated to enhance CEH activity is being explored. In summary, by delineating the pathways involved in CEH regulation, our research will provide new information that can eventually be helpful in development of strategies for prevention of coronary heart disease.
Norbert F Voelkel, MD
Dr. Voelkel is in charge of the Translational Research program of the Pulmonary Division with a focus on pulmonary hypertension and also on COPD/emphysema.
The pulmonary hypertension program will establish a mechanism for the detection of early pulmonary hypertension in adults and children--in particular in patients with collagen-vascular disorders, sickle cell disease and sarcoidosis. Animal models have been established to explore the immune regulation of lung vascular remodeling and right ventricular hypertrophy and failure and to test anti-angiogenic drugs' potential to reverse severe established pulmonary hypertension.Together with Dr. Lori Sweeney (Endocrinology) a program has been established which explores the role of estrogens in the development of pulmonary hypertension.
In the COPD area the interest is in molecular characterization of various COPD phenotypes and in the investigation of emphysema pathobiology in non-smokers.
The laboratory provides 3 different mofels of emphysema to explore whether an asthma-like reprograming of the immune system protects against emphysematous lung destruction and whether acrolein--(contained in cigarette smoke) causes emphysema. The auto-immune aspects of COPD/emphysema are also under investigation--both in the laboratory and in the clinic.
Clinical Research Activities
A diversity of clinical research is being
performed by members of the Division of Pulmonary and Critical
Care Medicine at both Virginia Commonwealth University and
the McGuire Veterans Affairs Medical Center. Active research
protocols intentionally involve collaborative efforts between
Division investigators and investigators from other VCU
Divisions and Departments as well as colleagues from other
institutions. Further, Division investigators participate
in multicenter pharmaceutical industry-sponsored clinical
trials. Current and recently completed clinical research
projects are described below.
Lisa Brath, MD
Dr. Brath is examining the role of outcomes
evaluation of an asthma specialty clinic in an indigent
population.
Paul Fairman, MD
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Dan Grinnan, MD |
Drs. Grinnan and Fairman collaborate on clinical research in pulmonary hypertension. A registry has been established to serve as a basis for a clinical research efforts. A primary goal for the Pulmonary Hypertension program is early detection of pulmonary hypertension in adults and children. Efforts are focused on patients at high risk for the disease including those with collagen-vascular disorders, sickle cell disease and sarcoidosis. Evaluations will build on current collaborations with Cardiology, Rheumatology, and the Sickle Cell Program.
A second effort seeks to determine the prevalence and severity of symptoms in Pulmonary Hypertension program patients near the end of death. It will also determine the prevalence of hospice care and palliative services in patients dying with pulmonary hypertension. The ultimate aim is to improve care for all Pulmonary Hypertension program patients. This is a collaborative effort with Palliative Care.
The Pulmonary Hypertension Service also participates in industry related trials.
Ram Rao, MD
Dr. Rao is developing programs and policies designed to
improve public health practice, particularly as it relates
to tuberculosis control. In collaboration with Dr. Betty
Ann Johnson, Associate Professor of Medicine and director
of the VCU Student Health Service, Dr. Rao is aiming to
develop and validate an effective risk assessment tool as
a predictor of tuberculosis infection. The results of this
multi-year project will provide data on prevalence of various
tuberculosis-related risk factors in the college health
population as well as provide a unique insight into the
correlation between these factors and tuberculosis infection.
In an additional collaboration with Dr. Daniel Henry, Professor
of Radiology, in the Department of Radiology, Dr. Rao is
developing and validating a computer-based, standardized
approach to chest radiographic interpretation for diagnosis
of pulmonary tuberculosis. The system, when perfected, will
ultimately allow comparison of multiple chest radiographic
interpretations to be handled electronically. The goal is
to reduce the ambiguity often associated with standard textual
interpretations.
Curtis Sessler, MD
Dr. Sessler participates in a wide variety of ICU-based
clinical research activities. He has served as VCU's Principle
Investigator for multicenter clinical trials addressing
novel treatments for ARDS, sepsis, and severe infections.
His current research interests focus on three primary areas:
Sepsis and multiple organ failure, prevention of nosocomial
infection, and agitation and sedation in the ICU. Current
and recently completed protocols address investigation of:
1) mechanisms of septic shock, including cannabinoid receptors,
2) the epidemiology of multiple organ failure, 3) the role
of circulating adhesion molecules in sepsis and critical
illness, 4) hand washing, backrest position, and central
venous catheter management in prevention of nosocomial infection,
5) development and validation of a new sedation-agitation
scale, 6) the epidemiology of agitation and delirium in
the ICU. Dr. Sessler collaborates closely with investigators
from the VCU Department of Nursing, Department of Pharmacology
and Toxicology, Department of Pharmacy, Divisions of Epidemiology,
and Quality Health Care in the Department of Medicine, and
other members of the Pulmonary and Critical Care Division.
He also collaborates with investigators from other leading
medical centers on several projects. He is an active mentor
for residents and fellows in ICU-based clinical research,
several of whom have received recognition at regional and
national meetings.
Wes Shepherd, MD
Dr. Shepherd's primary focus is in the area of interventional pulmonology. This includes advanced bronchoscopy techniques such as rigid bronchoscopy, YAG laser, electrocautery, photodynamic therapy and many others. It also includes pleural procedures and other diagnostic bronchoscopy tools such as endobronchial ultrasound and electromagnetic navigational bronchoscopy. Current research projects include the placement of fiducial markers into lung tumors to help study and improve the delivery of stereotactic radiotherapy in relation to tumor motion. Future research projects may also include bronchoscopic treatments for asthma and COPD.
Daniel Bechard, MD
Dr. Bechard is principal investigator on two industry-sponsored
trials. The Bio-Technology Oxandrolone Trial is a Phase
III study on the effect of anabolic steroids on respiratory
muscle strength in patients with severe chronic obstructive
lung disease and weight loss. Additionally, Dr. Bechard
is the principal investigator for the Organon pulmonary
embolism trial, an international open-label trail comparing
a once-daily pentasaccharide heparinoid versus unfractionated
heparin in the initial management of acute pulmonary embolism.
The endpoint is recurrence of thromboembolic events and
death.
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