Category: Research Area

Daniel L Minor, Ph.D.

Research Interests:
Membrane proteins; potassium channels, calcium channels

Summary:
Hearts, brains, muscles, and senses require electrical signals to function. We aim to understand the basic cellular components responsible for generating electrical activity. We focus on understanding the structure, function, and regulation of ion channels from a high-resolution viewpoint, understanding how channel mutations cause disease, and on developing new tools for controlling channel function.

Video A Universal CaM Switch Changes the Kv7 Channel

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Takashi Mikawa, M.S., Ph.D.

Research Interests:
Morphogenesis, development, body axis, patterning, cell-to-cell communication, cell architecture, cell fate diversification, cardiovascular system, cardiac conduction system, central nervous system, haemodynamics, growth factor signaling.

Summary:
The establishment of extremely complicated structures and functions of our organ systems depends upon orchestrated differentiation and integration of multiple cell types. Our group focuses to explore a common developmental plan for successful organogenesis, by investigating the mechanisms involved in the differentiation and patterning of the cardiovascular and central nervous systems.

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Michael A Matthay, M.D.

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.

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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Wendell A Lim, Ph.D.

Research Interests:
Signal transduction, synthetic biology, systems biology, structural biology, protein-protein interactions, cell motility, MAP kinase cascades, GTPase pathways

Summary:
Wendell Lim’s Lab is working on creating a detailed instruction manual – a sort of user’s guide – that explains how biochemical circuits control a cell’s function and ultimately its fate. The long-term goal is to use the instruction manual to help scientists design cells to deliver therapeutic payloads, repair cancerous lesions, or attack microscopic pathogens. Cells are complex mechanical and sensing devices that can carry out highly complex tasks, such as secreting antibodies or forming repair structures like blood clots and bone. Cells contain signaling pathways that take in and integrate vast amounts of information about the cells’ environment, and they process and use this information to make complex decisions about how to respond to changing environmental conditions. If more is understood about how these processes work, there is the potential to change cells and help solve problems in biotechnology or health, and to treat disease more rationally.

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Randall J Lee, M.D., Ph.D.

Research Interests:
Arrhythmias, radiofrequency catheter ablation, implantable cardioverter/defibrillators, genetics, gene therapy, tissue engineering, stem cells, cell transplantation, biopolymers, antibodies, myocardial reconstruction/regeneration

Summary:
The research program integrates the disciplines of cell biology, bioengineering and cardiology. A tissue engineering approach is being used to investigate the potential application of cardiovascular reconstruction/regeneration. The use of stem cells and engineered polymer scaffolds are being investigated in heart attach models to determine their usefulness and safety in repairing damaged heart tissue.

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Stephen C Lazarus, M.D.

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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Pui-Yan Kwok, M.D., Ph.D.

Research Interests:
Genetic analysis of complex traits, DNA technology development

Summary:
We are developing efficient methods to analyze single DNA molecules and applying molecular genetic tools to identify genetic factors associated with complex human traits such as longevity, sudden cardiac arrest, stroke, psoriasis, lupus, and kidney transplantation outcome. We are also conducting studies to identify genetic factors associated with drug response. The overall goal of our research is to develop the tools for genetic analysis of whole genomes and apply these tools to elucidate the genetic factors associated with common human diseases and phenotypes. The sequencing of the human genome and the mapping of common genetic variation by the International HapMap Consortium, in which our lab participated, have inspired an explosion of new technologies, accelerating identification of genetic susceptibility loci. Our phenotypes of interest include kidney transplantation outcomes, longevity, pharmacogenetics of membrane transporters, sudden cardiac death, psoriasis, skin cancer and brian vascular malformations and hemorrhage.

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Theodore W Kurtz, M.D.

Research Interests:
Molecular Genetics of Complex Disease, Genetic Models of Hypertension and the Metabolic Syndrome, Transcription Modulating Drugs

Summary:
Hypertension affects 30% of the population and is a major cause of stroke, kidney failure, and heart disease. Patients with hypertension are also at increased risk for diabetes. Our laboratory is studying genetic mechanisms that promote increased blood pressure with the goal of identifying new opportunities for the prevention and treatment of hypertension, diabetes, and cardiovascular disease.

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Ronald M Krauss, M.D.

Research Interests:
Summary:
Lipoprotein metabolism and risk of cardiovascular disease

Despite recent advances in treatment, cardiovascular disease (CVD) remains the leading cause of death in the US and will soon achieve this status globally. Our group’s research is aimed at addressing three major challenges for reducing this enormous disease burden. First, standard diagnostic procedures do not identify a high proportion of children and adults who are at risk for CVD. We have developed and implemented a sophisticated new procedure that, by analyzing individual lipoprotein particles, provides more specific information than that afforded by ordinary cholesterol testing, and hence is capable of improving both the assessment and management of CVD risk. Second, dietary and lifestyle guidance has failed to substantially impact CVD risk factors, particularly those related to overweight and obesity. We have demonstrated that carbohydrate restriction can reverse the high risk lipid profile found in a high proportion of overweight and obese individuals even without weight loss, and that this effect is independent of saturated fat intake. These findings have helped support dietary guidelines that place a greater emphasis on limiting refined carbohydrates than fats. Third, despite the awareness of wide interindividual variability in response to treatments aimed at reducing CVD risk, the potential benefits of applying genomic tools for developing personalized approaches for maximizing CVD risk reduction have not been realized. A major component of our research program has been the application and development of genomic methodology for dissecting genetic influences on the therapeutic responses to statins, the most widely prescribed class of drugs for reducing CVD risk.

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Laura L Koth, M.D.

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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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.

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