Category: Pulmonary Development and Lung Disease

Pulmonary biology and disease


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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Andy Chang, Ph.D.

ChangA

Research Interests:

Acute oxygen and metabolic sensing in cardiopulmonary regulation and disease

Summary:

To maintain optimal oxygen delivery to tissues, there is constant regulation of respiratory and cardiovascular systems by mechanisms that act on different time scales. On a fast time scale, a small chemosensory organ called the carotid body senses decreases in blood oxygen to increase breathing within seconds. The carotid body can also regulate cardiovascular function acutely, and carotid body hyperactivity contributes to disease progression in hypertension, heart failure, and metabolic syndrome. Using the mouse as our primary model, we aim to identify the molecular mechanisms that mediate the carotid body’s ability to detect changes in blood oxygen as well as other metabolic signals, such as carbon dioxide and acid. One long term goal is to apply this knowledge to manipulating carotid body activity in the treatment of cardiovascular disease and metabolic syndrome.

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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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Jason R. Rock, PhD

Rock

Research Interests:
Stem cells in lung development, maintenance, and disease

Summary:
We investigate how the many epithelial and stromal cell types of our lungs are generated during development, maintained for a lifetime and regenerated following injury. To do this, we use in vivo and in vitro models to identify and test the progenitor capacity of putative stem cell populations. We posit that aberrant stem cell behaviors explain many features of common lung diseases such as mucous cell hyperplasia and pulmonary fibrosis. For this reason, we study the molecular mechanisms and environmental influences (i.e., niche) that regulate the division and differentiation of stem cells along various lineages. Our ultimate goal is to identify genetic, molecular and cellular therapies for the treatment of lung disease.

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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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Michael J Mann, M.D.

Mann

Research Interests:
1. Molecular/cellular biology and molecular genetics of atherosclerosis and heart failure. 2. Development of hybrid surgical and molecular/cellular therapies for heart disease. 3. Stem and progenitor cell transplantation for cardiovascular regeneration. 4. Cardiovascular tissue engineering. 5. Reduction to clinical practice of current methods in genetic, molecular and cellular disease intervention. 6. Novel targeted molecular therapies for lung cancer. 7. Molecular profiling of cancers for personalized medicine. 8. Development of novel methods of in vivo/ex vivo gene therapy and gene transfer. 9. Novel approaches to therapeutic neovascularization for coronary and peripheral ischemic disease. 10. Cardiovascular cell cycle biology. 11. Myocardial gene therapy.

Summary:
Dr. Mann’s research focuses on the molecular and cellular biology of heart disease with an emphasis on practical ways to develop new treatments for heart failure. These involve potential gene and molecular therapies, combinations of molecular and cell-based treatments with surgical reconstruction, and evaluation of novel materials for the development of bioartificial replacements of lost or damaged heart tissue.

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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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