Category: Developmental Biology and Congenital Anomalies


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

Kornberg

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.

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Yuet W Kan, M.D. , D.Sc.

Kan

Research Interests:
The mechanisms of globin production and exploring novel ways of inserting genes into mammalian cells; investigating newer approaches for fetal diagnosis of genetic disorders

Summary:
Sickle cell anemia and thalassemia are the most common genetic diseases and affect people of African, Mediterranean, Middle Ease and Southeast Asian origins. Our laboratory has pioneered the diagnosis of these conditions by DNA tests and is currently investigating the use of patient specific stem cells for their treatment.

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Natalia Z Jura, PhD

Research Interests:
Receptor tyrosine kinases, kinase regulatory mechanisms, membrane proteins, feedback regulation of cell signaling

Summary:
We study basic mechanisms of cellular signaling by Receptor Tyrosine Kinases with a goal to understand how cells receive and process growth signals provided by the neighboring cells and the extracellular milieu. Receptor Tyrosine Kinases are single pass transmembrane receptors that catalyze tyrosine phosphorylation upon activation of their intracellular kinase domains. These receptors are principal regulators of growth and survival signals in cells and therefore frequently become deregulated in human diseases. We are interested in understanding how the kinase activity of these receptors is regulated by ligand binding and how the receptors associate with their regulatory components during the activation process. By combining biochemistry and cell biology we are studying these processes in the reconstituted membrane systems in vitro and in the plasma membrane of the living cells. We also use crystallography to gain an atomic resolution insight into Receptor Tyrosine Kinase regulation that will help us design new approaches for therapeutic intervention.

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Jura Lab Website

 


Holly A Ingraham, Ph.D.

Ingraham

Research Interests:
Summary:
Our research is focused on development of endocrine and brain regions that contribute to energy balance and reproduction. We concentrate on NR5A nuclear hormone receptors that specify cell fate in developing endocrine organs and the hypothalamus using structural biology, biochemistry and physiology.

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Guo Huang, Ph.D.

Huang

Research Interests:
Comparative study of heart development and regeneration, ischemic heart diseases, stem cell, cardiomyocyte proliferation, regenerative biology

Summary:
The ability to regenerate damaged or lost tissues varies dramatically across organisms and developmental stages. For example, heart regeneration is robust in adult zebrafish and newborn mouse while very limited in adult mouse and human. This presents a particular problem for patients with a heart attack who suffer from a significant loss of heart muscle cells and subsequent life-threatening functional deterioration of the heart.

By taking a comparative approach to study regenerative versus non-regenerative heart repair processes in zebrafish and mouse, we seek to uncover ancestrally conserved injury responses and more importantly, to identify the signals blocking regeneration in the mammalian heart and consequently new treatment strategies for heart diseases.

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Julien I Hoffman, M.D., F.R.C.P.

Research Interests:
Pathophysiology of myocardial ischemia

Summary:
My research investigates the way in which the complex muscular architecture of the human heart functions, and what role different components play in heart failure. Current hypotheses of ventricular architecture emphasize the interaction of spiral and circumferential muscle layers, but one major hypothesis that there is a single folded muscular band is much in dispute. We know that the adult pattern is already complete at 14 weeks gestation, but there is no information about how the primitive cardiac tube becomes this complex multilayered structure. My colleagues and I have shown that different components of this muscle band may be affected in diastolic heart failure, and are seeking further information about how components of the band arise and how each component may be affected by disease.

I have ongoing research into the epidemiology of congenital heart disease but no specific problems are being studied at the moment.
Most of my previous research involved the control of the regional coronary circulation, with particular reference to the mechanisms of subendocardial ischemia. Although I am not actively working in this field now, I am collaborating with some bioengineers who are studying these problems.

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Samuel Hawgood, M.B., B.S., M.D.

Hawgood

Research Interests:
Structure and function of surfactant apoproteins

Summary:
Our research activity is focused on the biology of the pulmonary alveolus with a particular emphasis on the structure and function of the pulmonary surfactant apoproteins. The human lung is made up of some 500 million alveoli each with a diameter of 200 microns and a septal wall thickness of only 5-8 microns. The large surface area provided by this foam-like architecture is ideal for rapid respiratory gas exchange but necessitates some unique biological answers to the threat to structural stability posed by the problem of high surface tension and the constant exposure to environmental pollutants, allergens and microbes. Pulmonary surfactant, a lipoprotein secretion of the alveolar epithelial type II cell, stabilizes alveolar structure at low transpulmonary pressures by reducing the retractile surface forces that would otherwise act to collapse the lung at end expiration. The surfactant apoproteins also act as components of the pulmonary innate defense system protecting the lung from inflammation and infection.

A derangement of alveolar stability, secondary to a developmental deficiency of surfactant, is the major factor in the pathogenesis of the respiratory distress syndrome of the newborn (RDS). My interest in the biology of surfactant grew from clinical experience in neonatology where RDS is a major cause of neonatal death. I moved to UCSF in 1982 as a research fellow with Dr. John Clements, the scientist who discovered surfactant in the late 1950’s. He started his own laboratory, focused on the proteins associated with surfactant, in 1984. By 1985 our laboratory had identified three novel surfactant-associated proteins, now known as SP-A, SP-B and SP-C, and had derived their primary structures from full-length cDNA and genomic clones. In 1993, Erica Crouch in St. Louis described a fourth protein, SP-D. The higher-order structure, genetic regulation, metabolism, and function of these proteins have been the focus of our research since that time.
We now know that the surfactant proteins have important roles in the activity of surfactant, particularly the ability to rapidly spread phospholipids at the alveolar surface. The proteins also regulate surfactant turnover and metabolism in the alveolus and play a part in non-antibody mediated response to infection and inflammation in the alveolus. The biology of these proteins is complex and they apparently function as interacting hetero-oligomers to mediate their multiple effects on surfactant biology. At least two of the surfactant proteins, SP-B and SP-C, are present in exogenous surfactants approved for clinical use and fatal human disease has been linked to inherited mutations in both these proteins. This clear link to human disease provides a strong rationale to obtain a detailed understanding of their structure and function.

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Rik M Derynck, Ph.D.

Derynck

Research Interests:
Transmembrane TGF-a and TGF-b receptor signaling in cell proliferation and differentiation.

Summary:
Dr. Derynck studies signaling mechanisms that regulate the generation of bone, muscle and fat cells and how these cells derive from mesenchymal stem cells. This knowledge is used to direct mesenchymal stem cells and pre-adipocytes toward the generation of bone and muscle tissues.

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Bruce R Conklin, M.D.

Conklin

Research Interests:
Engineering Hormone Signaling Pathways In Vivo

Summary:
Hormone receptors direct the development and function of complex tissues, including those found in the cardiovascular system. The focus of our research is on the largest known family of receptors for hormones and drugs, the G protein coupled receptors. We combine genetic engineering, stem cells and new computer programs to find new treatments of cardiovascular disease.

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

Chuang

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.

 

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Benoit G Bruneau, B.Sc., Ph.D.

Bruneau

Research Interests:
Heart development, congenital heart disease, chromatin, embryogenesis, transcription

Summary:
Our laboratory studies the genes that direct a cell to become a heart cell, focusing on the machinery within each cell that turns genes on or off. Many of these factors are implicated in human congenital heart disease, and our studies also focus on understanding the basis of these diseases.

 

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