Category: Site Parnassus


Stanton A Glantz, Ph.D.

Glantz

Research Interests:
Mechanics of cardiac function (experimental and theoretical); environmental tobacco smoke and tobacco control policy

Summary:
Dr Glantz studies the effectiveness of different tobacco control strategies, particularly in the context of large state-run tobacco control programs, how the tobacco industry works to systematically distort the scientific process and animal and human studies of the effects of passive smoking on the heart.

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David G Gardner, M.D.

Gardner

Research Interests:
Cardiovascular endocrinology, natriuretic peptides, natriuretic peptide receptors, vitamin D, nuclear hormone receptors, growth and hypertrophy in cardiovascular system and kidney, obesity-related cardiomyopathy.

Summary:
Our laboratory is interested in understanding the role that hormones play in the control of growth and function in the cardiovascular system (heart and blood vessels). We are particularly interested in vitamin D and the natriuretic peptide hormones, two classes of hormones that have beneficial effects on cardiovascular function.

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Jeffrey R Fineman, M.D.

Fineman

Research Interests:
Endothelial regulation of the pulmonary circulation during normal development and during the development of pediatric pulmonary hypertension disorders. Endothelial dysfunction in pediatric pulmonary hypertension

Summary:
Pulmonary hypertension, high blood pressure in the lungs, is a serious disorder in subsets of neonates, infants, and children. These include newborns with persistent pulmonary hypertension of the newborn (PPHN), children with congenital heart defects, and teenagers and young adults with primary pulmonary hypertension. The vascular endothelium (the cells that line the blood vessels in the lungs), via the production of vasoactive factors such as nitric oxide and endothelin-1, are important regulators of the tone and growth of pulmonary blood vessels. We utilize an integrated physiologic, biochemical, molecular, and anatomic approach, to study the potential role of aberrant endothelial function in the pathophysiology of pulmonary hypertensive disorders. To this end, we utilize fetal surgical techniques to create animal models of congenital heart disease, and investigate the early role of endothelial alterations in the pathophysiology of pulmonary hypertension secondary to congenital heart disease with increased pulmonary blood flow. Our clinical research interests include the use of pulmonary vasodilator therapy for pediatric pulmonary hypertension, and the use of peri-operative BNP levels as marker of outcome following repair of congenital heart disease.

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John Vincent Fahy, M.D.

Fahy

Research Interests:
Mechanism oriented studies of airway disease in human subjects

Summary:
Our research involves studies in people with airway diseases such as asthma, cystic fibrosis, and chronic bronchitis. We are involved in clinical trials of new and established treatments on the one hand and in clinical studies designed to improve understanding of mechanism of disease on the other. For clinical trials, we often collaborate with other CVRI investigators or investigators at other institutions to compare the efficacy of new and established drugs. In conducting clinical trials, we are usually interested in exploring the effects of drugs not just on measures of lung function but also on measures of airway inflammation and remodeling. For this purpose, our laboratory has developed expertise in measuring markers of inflammation and remodeling in samples of sputum or in samples of airway fluids and tissue collected during bronchoscopy. Our lab is particularly experienced in measuring gene expression using gene chips and PCR and in quantifying pathology using a rigorous method of quantitative morphology called stereology.

For our research on mechanisms of airway disease, we are particularly interested in abnormalities of airway epithelial cells (the lining cells of the airway) and in abnormalities in airway mucus. Mucus abnormalities are common in lung diseases, and we are interested in finding out the specific mucus abnormalities that are characteristic of different lung diseases such as asthma and cystic fibrosis. Recently, we have begun to explore the physical properties of airway mucus – thickness, stickiness, and adhesiveness – using an instrument called a rheometer. The rheology of airway mucus has not been investigated in detail, but the research resources of the CVRI are well suited to making progress in this area. For example, in our clinical laboratories in the CVRI, we can collect induced sputum from volunteers in a carefully controlled way, and in our bench laboratories we can make careful rheological measures. These rheologic measures are allowing personnel in our lab to explore new strategies for breaking up the mucus that normally clogs airways.

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Joanne N Engel, M.D., Ph.D.

Engel

Research Interests:
Bacterial Pathogen-Host Cell Interactions

Summary:
My laboratory is interested understanding and exploiting the complex interplay of microbial pathogens with eukaryotic cells. To that end, we have investigated the key processes of microbial attachment and entry, intracellular survival, and host cell injury in the context of two important human pathogens, Pseudomonas aeruginosa (PA) and Chlamydia trachomatis (CT). Each of these microorganisms has developed a unique strategy for successful survival that involves subverting and exploiting host cell pathways. Dissecting these processes will allow the development of new diagnostics, therapeutics, and vaccines and will provide a unique window into eukaryotic cell biology.

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Michael S Conte, M.D.

Conte

Research Interests:
Aortic reconstruction, carotid artery disease, lower extremity arterial occlusive disease, diabetic vascular disease

Summary:
Our laboratory studies the healing process in blood vessels which currently limits the long term success of procedures like angioplasty and bypass surgery. Our goals are to develop new drug and molecular therapies to prevent failures due to vessel re-narrowing, and to better identify patients at increased risk.

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Ronald I Clyman, M.D.

Clyman

Research Interests:
Cardiology, Cell Biology, Developmental Biology, Neonatology, Neonatal Cardiology

Summary:
The ductus arteriosus is a vital fetal blood vessel that diverts blood away from the fetus’s lungs and towards the placenta during life inside the uterus. After birth it is essential that the ductus arteriosus constricts and obliterates itself so that the normal postnatal pattern of blood flow can be established. Essentially all full term infants will have closed their ductus by the third day after birth. Preterm infants of less than 30 weeks gestation have a high chance of having a persistently open or patent ductus arteriosus (PDA). If the ductus arteriosus remains open it contributes to the development of several neonatal morbidities: prolonged ventilator dependency, pulmonary hemorrhage, pulmonary edema, chronic lung disease and necrotizing enterocolitis. Our laboratory has been studying the factors that regulate normal closure of the ductus arteriosus in full term infants and abnormal persistent ductal patency in preterm infants. Approaches used to study this problem are: controlled clinical trials, integrated whole animal physiology, in vitro organ culture, and cell biology.

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Israel F Charo, M.D. , Ph.D.

Charo

Research Interests:
Structure and Function of Chemokine Receptors

Summary:
The goal of our research is to use gene targeting and creation of transgenic mice to study the in vivo functions of chemokines and chemokine receptors. Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and block HIV�1 infection of target cells through interactions with chemokine receptors. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis, glomerulonephritis, and inflammatory lung disease. The chemokine family is growing rapidly. Our laboratory focuses primarily on two chemokines: monocyte chemoattractant protein 1 (MCP-1) and fractalkine, a recently described and structurally unique chemokine.

 

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Harold A Chapman, M.D.

Chapman

Research Interests:
Antigen presentation by MHC class II molecules important to immunity and autoimmunity and extracellular matrix remodeling important to cell migration and tissue repair

Summary:
The Chapman lab is focused on basic and biomedical aspects of lung injury and tissue remodeling. Currently the lab is exploring the process of epithelial to mesenchymal transition (EMT) in the lung, a process whereby epithelial lining cells of the lung become reprogrammed to migrate and activate a fibrotic program. The process is also implicated in progression of lung cancer and the lab is exploring the mechanisms by which EMT contributes to lung fibrosis and cancer metastasis.

 

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Carolyn S. Calfee, M.D., MAS

Calfee

Research Interests:
Acute lung injury, acute respiratory distress syndrome, cigarette smoking, molecular epidemiology, biomarkers

Summary:
Dr. Calfee’s primary academic focus is the prevention, diagnosis, prognosis, and treatment of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Current research projects include: (1) the role of biomarkers in investigating ALI/ARDS pathogenesis, early diagnosis, treatment, and prognosis; (2) the role of cigarette smoke exposure in susceptibility to lung injury; and (3) novel treatments for acute lung injury.

 

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James K Brown, M.D.

Brown

Research Interests:
Protease signaling

Summary:
In asthma, abnormal growth of airway smooth muscle cells contributes to difficult breathing. Mast cells are a prominent inflammatory cell in the airways of these patients, and during allergic reactions, mast cells release a substance called tryptase. Our work focuses on understanding how tryptase activates smooth muscle cells to grow.

 

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Homer A Boushey, M.D.

Boushey

Research Interests:
Bronchial hyperreactivity in asthma. Effects of viral infection on airway function. Regulation of airway mucous secretion and vascular permeability.

Summary:
Dr. Boushey’s goal is to develop ways of curing and preventing asthma. His research takes advantage of new methods for detecting viruses and bacteria to examine relationships among the allergens and bacteria found in the environment, bacteria in the gastrointestinal tract, the function of the immune system, and the development of asthma.

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