Category: Pulmonary Development and Lung Disease

Pulmonary biology and disease


Jeffrey O. Bush, Ph.D.

Research Interests:

Signaling control of mammalian morphogenesis and congenital disease

Summary:

Our lab studies basic mechanisms by which signaling between cells coordinates mammalian morphogenesis. Understanding this control has significance beyond its fundamental importance in development since birth defects are the leading cause of death for infants during the first year of life. We utilize multiple approaches based in mouse genetics to understand fundamental signaling processes as they relate to development and disease with particular foci in the craniofacial and respiratory systems. In addition to mouse genetics approaches, we utilize human ES/IPSCs, biophysical approaches, multiomics, and live imaging to understand the cellular and molecular control of morphogenesis.

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Brian B. Graham, M.D.

Research Interests:

Pulmonary hypertension and pulmonary vascular inflammation, and cardiac angiogenesis.

 

Summary:

Our research group investigates pulmonary hypertension, a disease of the lung blood vessels. The major focus of our research is how the immune system contributes to the disease. The goal of our work is to discover new treatment approaches to help prevent or reverse this disease.

 

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Mark Looney, M.D.

 

Research Interests:

Pulmonary and Critical Care Medicine, acute lung injury, acute respiratory distress syndrome, blood transfusions, transfusion-related acute lung injury, neutrophils, neutrophil extracellular traps, platelets, lung transplantation

Summary:

My laboratory is broadly interesting in study innate immune biology in the normal and injured lung.  Using pre-clinical models of acute lung injury, we have focused on neutrophils and platelets, the latter being a bon a fide immune cell with powerful inflammatory potential.  One consequence of platelet-neutrophil interactions is the formation of neutrophil extracellular traps (NETs), which we study in both sterile and pathogen-induced lung injury models.  We are determining the mechanisms by which platelets trigger NETs and novel pathways to target NETs—which we have discovered are overall barrier disruptive in the lung.   

We also use two-photon intravital lung microscopy as a tool for discovery.  Using this technique, we have determined that the lung is a major source of mature platelet production in mice.  Furthermore, megakaryocytes reside in the extravascular lung and may have potent local immune effects.  The lung also contains a wide-range of hematopoietic progenitors, which have the capacity to leave the lung and engraft in the bone marrow for multi-lineage blood production.  We are determining the niche-promoting factors responsible for hematopoietic progenitor residence in the lung and the contributions of these cells to the local immune repertoire.

We have an expanding interest in lung transplantation studies, including ischemia-reperfusion injury (primary graft dysfunction) and modeling chronic lung allograft dysfunction (bronchiolitis obliterans).  We use the mouse single lung transplantation technique for these studies and to create lung chimeras for investigation.

UCSF Profiles Page: http://profiles.ucsf.edu/mark.looney


Tien Peng, M.D.

tienpeng2

Developmental pathways in the maintenance of adult tissue homeostasis

Our laboratory is interested in studying how key developmental pathways continue to persist in adulthood to maintain normal homeostatic organ function. We are particularly focused on the mesenchymal cell types (e.g. fibroblasts, pericytes, and etc.) that are poorly understood and lack precise anatomical definition, but are integral to the structural integrity and function of adult organs such as the lung.

 

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Ian Bass Seiple, Ph.D.

 

Seiple

Research Interests:

Synthesis of biologically active small molecules

Summary:

Despite centuries of innovation, chemistry is often still the limiting factor in the development of small molecule drug candidates, molecular probes, or novel chemical libraries. Many molecules that have tremendous biological potential are challenging to modify with known chemical methodologies. The overarching goal of our program is to develop practical methods for the synthesis of molecules that have previously been inaccessible. Many of our current projects are focused on the synthesis of novel antibiotics that can be used to treat life-threatening infections of the heart, lungs, and upper respiratory tract.

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David F Teitel, M.D.

Teitel

Research Interests:
Pediatric cardiology, developmental cardiovascular physiology, cardiac mechanics, pediatric interventional cardiac catheterization, computer technology in cardiology, heart center administration, medical education, digital technology in learning, bioinformatics.

Summary:
Congenital heart disease is extremely common, occurring in about 1% of all births. My goals are to advance our knowledge of heart function in such infants and children, and to develop new methods to treat them, using medicines and catheter based techniques rather than surgery.

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Anthony K Shum, M.D.

Shum

Research Interests:
Autoimmune lung disease, interstitial lung disease, ER stress, lung injury, lung fibrosis, lung autoantigens

Summary:
The Shum lab is interested in understanding the immune mechanisms that lead to lung inflammation and fibrosis in patients with autoimmune disorders. Through human and mouse studies, we seek to define the critical factors that lead to autoimmune lung disease in order to speed the development of diagnostic tests and treatments for patients.

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Dean Sheppard, M.D.

Sheppard

Research Interests:
In vivo function of integrins and molecular basis of lung diseases

Summary:
Dean Sheppard’s laboratory studies how cells respond to and modify their surroundings using receptors called integrins. They have found important roles for integrins in lung and kidney fibrosis, septic shock, acute lung injury, asthma and stroke and are testing drugs targeting integrins in animal models and in people affected by these diseases.

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Michael A Matthay, M.D.

Matthay

Research Interests:
Alveolar epithelial transport under normal and pathologic conditions. Resolution of pulmonary edema Mechanisms of Acute Lung Injury

Summary:
My research program is focused on identifying mechanisms responsible for fluid transport across the alveolar epithelium using cell, molecular, and in vivo models. In addition, our group is focused on understanding the mechanisms responsible for the development and resolution of pulmonary edema and acute lung injury in critically ill patients with acute respiratory failure. The studies include experimental and human-based studies designed to understand the pathogenesis of acute respiratory failure and to test potential new therapies. The work is supported primarily by grants from the National Heart, Lung, and Blood Institute.

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Dengke Ma, Ph.D.

Ma

Research Interests:

Genetic approaches to understanding physiology and diseases, oxygen-modulated metabolism and behavior; brain-heart-lung interaction and interoception; ischemic disease and tolerance; novel genes and pathways evolutionarily conserved in C. elegans and humans.

Summary:
As humans, we drink when thirsty, eat when hungry, and increase our breathing and heart rates when short of oxygen. How do we (our bodies) know when and how to respond to changes in internal bodily states (e.g. loss of nutrient or oxygen)? Genes and traits that facilitate such underlying mechanisms confer great advantages for animal survival and are strongly selected for during evolution. Using both C. elegans and tractable mammalian model systems, we seek to understand the molecular, cellular and neural circuit basis of how animals sense and respond to changes in internal metabolic and energetic states to elicit behavior and maintain homeostasis. Dysfunction of these fundamental physiological processes leads to many disorders, including obesity, diabetes, neurological and cardiovascular diseases.

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Stephen C Lazarus, M.D.

Lazarus

Research Interests:
Role of inflammation in asthma and COPD, mucus hypersecretion.

Summary:
Asthma affects 5-10% of the US population, and deaths from asthma have increased for several decades. COPD is the 4th leading cause of death in the US. Understanding the mechanisms involved in these diseases and how best to treat them will contribute to better outcomes.

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Laura L Koth, M.D.

KOTH_image

Research Interests:
Sarcoidosis Granulomatous Lung Diseases T cells Monocytes chemokines

Summary:
Dr. Koth’s research program is structured around the study of samples from human research studies. With the breath of research techniques that can be applied to human samples to learn about disease, Dr. Koth is taking a direct approach in the study of lung diseases. Dr. Koth’s current focus involves understanding the inflammatory disease called sarcoidosis. This is not a disease as common as asthma, but it affects both young and middle aged people and causes significant morbidity and mortality. More awareness and funds are needed if we hope to understand the complicated biology of the disease. For example, many of the main immune subsets of the body are abnormally regulated in this disease. Most research has focused on the traditional T-cell. For example, it is thought that specific T cells are very activated and making inflammatory products which are contributing to and continuing the disease. However there are other immune cells that have not been studied adequately. Dr. Koth’s lab has taken an active interest in these other types of immune cells. One reason for this is that we have identified, using Genomics research, that specific transcripts in the blood actually predict whether a specific patient will have progressive disease or not. She and her lab are now pursuing a line of investigation to understand where this ‘biomarker message’ is coming from in order to be able to stop it.

Dr. Koth’s lab is also interested in using state-of-the-art technology to think about new therapies for this disease. We are looking into cutting-edge translational methods of expanding a type of immune cell responsible for down regulating the inflammatory process of the body. To perform these experiments in clinical trials will require significant financial support and we are seeking this input in order to move this very exciting potential treatment forward. The other aspect of my research program includes the development of a ‘center of excellence in sarcoidosis’. This program will be designed to include both excellence in clinical care and novel clinical studies. Developing clinical care standards is an important area in managing sarcoidosis patients since sarcoidosis is a chronic disease that may be active for 10-20 years or more. Thus, a full-service clinical care program would facilitate the creation of clinical management tools and treatment regimens (developed as products from clinical trials networks) to address three arms of care in sarcoidosis: 1) organ damage, 2) symptom control, and 3) psychosocial aspects of living with the disease.

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