Category: Pulmonary Development and Lung Disease

Pulmonary biology and disease

Thomas B Kornberg, B.A., Ph.D.

Research Interests:
Developmental regulation

Summary:
My laboratory investigates the mechanisms that pattern developing organs. We carry out our studies on the fruit fly, as it offers many advantages with its ready accessibility to histological analysis and the ease with which genetic manipulations can be made. We focus on two systems the fly wing and the fly lung. Both are model systems that offer opportunities to identify and characterize basic genetic and molecular mechanisms that are relevant to human development and disease.

UCSF Profiles Page

Akiko Hata, Ph.D.

Research Interests:
Mechanisms of growth factor signaling in the control of cell growth and differentiation of vascular cells

Summary:
Research in the Hata lab focuses on the role of the BMP/TGF signaling pathway in the maintenance of vascular homeostasis, control of vascular injury repair, and pathogenesis of vascular diseases, including idiopathic pulmonary arterial hypertension (IPAH), hereditary hemorrhagic telangiectasia (HHT), restenosis, and atherosclerosis. Our approach is to study gene mutations identified among patients with IPAH or HHT and elucidate how these gene products affect the signaling pathway as well as vascular physiology using both cell culture and animal models.

UCSF Profiles Page

Michael Gropper, M.D., Ph.D.

Research Interests:
Transfusion related acute lung injury, acute respiratory failure, acute respiratory distress syndrome, sepsis, ventilator associated pneumonia, resuscitation, mechanical ventilation, critical care outcomes

Summary:
My research interests are all focused on improving outcomes in critically ill patients in the ICU. These interests range from basic scientific questions regarding the mechanisms of harm from blood transfusions to asking about whether we efficiently utilize our precious resources, particularly at the end of life.

UCSF Profiles Page

Warren M Gold, B.A., M.D.

Research Interests:
Pulmonary physiology, exercise physiology, pulmonary vascular obstruction, early diagnosis, dyspnea, asthma, COPD, diffusing capacity.

Summary:

UCSF Profiles Page

Jeffrey R Fineman, M.D.

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.

UCSF Profiles Page

John Vincent Fahy, M.D.

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.

UCSF Profiles Page

David J Erle, M.D.

Research Interests:
Asthma, allergy and inflammation; functional genomics

Summary:
Asthma is an increasingly common disease that affects about 20 million American children and adults. We are working to understand how proteins made by the immune system act within the lungs to cause some of the most important problems experienced by people with asthma. We also work on understanding newly discovered ways in which genes are turned on and off during health and disease.

UCSF Profiles Page

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

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.

UCSF Profiles Page

Ronald I Clyman, M.D.

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.

UCSF Profiles Page

Pao-Tien Chuang, M.D. , Ph.D.

Research Interests:
Cell-cell signaling during mammalian development and in postnatal physiology

Summary:
We use mouse as a model system to understand how embryos develop. This knowledge is critical for understanding the basis of human congenital defects. Moreover, many adult diseases have their origin in development. Thus, our studies have important implications for developing stem cell therapy and identifying the cause of cancers.

UCSF Profiles Page

Harold A Chapman, M.D.

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.

UCSF Profiles Page

Carolyn S. Calfee, M.D., MAS

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.

UCSF Profiles Page