CVRI Scientists

Ion channels and arrhythmias

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

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.

Andy Chang, Ph.D.
Assistant Professor

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.

William F Degrado, Ph.D.
Professor

Research Interests:
De novo protein design, drug design, protein structure/function, membrane protein structure, integrins, antivirals, antibiotics.

Summary:
DeGrado's group works on the design of molecules that inform our understanding of biological processes. They also have developed small molecules drugs for various as potential pharmaceuticals, including antithrombotics, heparin reversal agents, antibacterials, and antiviral agents.

Michael D Grabe, Ph.D.
Associate Professor

Research Interests:
Membrane channels and transporters, molecular simulation, continuum electrostatics and elasticity theory

Summary:
Our lab uses computational methods to understand biological phenomena. We are primarily interested in the mechanical operation of ion channels and transporters, which move ions and small molecules across membranes. Additionally, we use theoretical approaches to explore how these membrane proteins work together to regulate ion homeostasis in organelles such as the lysosome and Golgi. Lastly, we are developing methodologies for predicting the stability of membrane proteins to understand how mutations give rise to a loss of function, improper trafficking or degradation.

Guo Huang, Ph.D.
Assistant Prof in Residence

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.

Lily Y Jan, B.Sc., M.Sc., Ph.D.
Professor

Research Interests:
Studies of potassium channels

Summary:
Ion channels such as potassium channels and calcium-activated chloride channels are important for the function of the heart, lung, and vasculature. Starting with molecular characterizations of the channel proteins, we try to understand how these channels work and how their activities are regulated under various physiological conditions

David J Julius, S.B., Ph.D.
Chair and Professor

Research Interests:

Summary:

Randall J Lee, M.D., Ph.D.
Prof of Clin Med

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.

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

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.

Daniel L Minor, Ph.D.
Professor

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.

Jeffrey E Olgin, M.D.
Professor and Chief

Research Interests:
Cardiac Electrophysiology, Arrhythmias, Mechanisms, Remodeling, Cardiac Fibrosis, Atrial Fibrillation, Cardiac Ablation, Mouse models, animal models, mouse electrophysiology, optical mapping, atrial fibrillation ablation, clinical trials.

Summary:

Jason R. Rock, PhD
Assistant Professor

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.

Ian Bass Seiple, Ph.D.
Assistant Prof in Residence

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. 

Lei Wang, Ph.D.
Associate Professor

Research Interests:
Design and encode novel amino acids to study biological processes and to develop new biotherapeutics.

Summary:
We build proteins in living cells using new amino acids. By harnessing the novel properties of these new building blocks, we probe biological processes in their natural settings and engineer unique biomolecules to understand mechanisms of cellular function and to develop new treatments of diseases.

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