Category: Research Area


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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Arthur Weiss, M.D., Ph.D.

Weiss

Research Interests:
Cell Surface Molecules and Molecular Events Involved in Lymphocyte Activation

Summary:
Dr. Weiss studies on how the functions of cells of the immune system are regulated. The immune system protects individuals from infections and malignancies. However, it is also involved in undesirable destructive responses, such as in autoimmune and allergic diseases as well as atherosclerosis and transplant rejection.

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Orion D Weiner, Ph.D.

Weiner

Research Interests:
Cell polarity, chemotaxis, actin cytoskeleton, cell signaling, cell migration, microscopy, biochemistry, neutrophils, systems biology, self-organization, inflammation, Rac, PI3Kinase, WAVE complex.

Summary:
Proper movement in response to cues from the outside world is as important for single cells as it is for drivers on a busy highway. If cues are misinterpreted or the movement goes awry, terrible accidents ensue, the delicate wiring of the nervous system fails, single-celled organisms can`t hunt or mate, the immune system ceases to function properly, and cancer cells spread from one part of the body to another. How do single cells, without the benefit of a brain, interpret the subtle micro-world of attractants and repellents to decide where to go? Our research focuses on dissecting the inner workings of the cellular “compass” used to guide cells on their journey. Because the core of the compass has been conserved over more than a billion years of evolution, we have been able to combine discoveries from yeast to humans to glimpse some rough outlines of the underlying machinery. However, many of the important connections are still missing. Our research focuses on identifying these key missing components and how they are wired together to process information with the hope that we can eventually make cells move when (and where) we want them to and stop them when we don’t.

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Lei Wang, Ph.D.

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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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Biao Wang, Ph.D.

WangB

Research Interests:
Obesity, diabetes, hormones, cAMP, kinase, signaling transduction, transcriptional regulation

Summary:
Type II diabetes mellitus accounts for 90-95% of all cases of diabetes, and this heterogeneous disorder afflicts an estimated 6% of the adult population in Western society. Energy imbalance by high calorie intake and/or lack of physical activity can lead to obesity, which is often associated with an increased risk of developing insulin resistance followed by type II diabetes. Our research is focused on understanding how circulating hormones modulate energy balance in multiple metabolic tissues, and how disruption of these hormonal actions contributes to pathophysiology of type II diabetes.

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Rong Wang, Ph.D.

Rong Wang photo copy

Research Interests:
Molecular Regulation of Mammalian Arterial Venous Specification

Summary:

Molecular Regulation of Arterial-Venous Programming in Development and Disease   

 

Research in my lab is focused on angiogenesis, or new blood vessel formation, which is a critical process in development and disease. My lab aims to advance the fundamental understanding of the cellular, molecular, and hemodynamic mechanisms underlying arterial-venous programming in normal and pathological angiogenesis. We use cutting-edge mouse genetics to delete or express genes in a cell lineage-specific and temporally controllable fashion in endothelial cells. This advance is crucial for the study of candidate genes in vascular function, especially when combined with sophisticated 5D two-photon imaging (3D + blood flow over time). These innovative approaches provide us with exceptional access to gene function in both healthy and pathological conditions in living animals. This basic approach is complemented by preclinical studies with patient samples in addition to our mouse models of disease. In particular, we investigate the molecular regulators governing arterial-venous programming – particularly the Notch, ephrin-B2, and TGF-beta signaling pathways – in both normal and pathological conditions.

 

 

Ongoing projects:

 

Vascular Development.  Our lab aims to identify molecular regulators of arterial and venous cell fate determination and morphogenesis in embryonic development. We primarily focus on the origin and morphogenesis of the dorsal aorta and cardinal vein, the first major artery-vein pair to form in the body.

 

Arteriovenous Malformation (AVM).  AVMs are severe vascular anomalies that shunt blood directly from arteries to veins, displace intervening capillaries, and bypass tissues. My lab studies the pathogenesis and regression of AVMs. We have a long history of investigation using animal models into Notch-mediated AVM pathogenesis as well as into potential treatments for the disease.

Arterial occlusive diseases and arteriogenesis.  The body responds to arterial occlusions by inducing arteriogenesis, or radial enlargement of arteries, to restore circulation to blood-deprived tissue. We are investigating pro-arteriogenic molecular regulators to uncover potential therapeutic targets, which may be used to enhance the body’s natural defense against arterial occlusive disease.

Cancer. Solid tumors induce arteriogenesis to support their growth. We investigate the molecular stimulators of arteriogenesis in tumor progression and regression, particularly in hepatocellular carcinoma (HCC), which is characterized by large and highly arterialized tumor masses in the liver. We study genes regulating tumor arterial growth and modify these genes to target tumor arterial supply and to inhibit HCC growth.

Ultimately, through these distinct but interconnected fields of study, we hope to identify novel drug targets and inform rational design of new therapeutics to treat human disease.

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Mark E Von Zastrow, Ph.D., M.D.

Von Zastrow

Research Interests:
Subcellular organization and dynamics of receptor-mediated signaling systems in eukaryotic cells.

Summary:
Our laboratory studies mechanisms by which receptors that control cardiovascular biology are regulated. These receptors are important therapeutic targets and their regulation is known to be disturbed in a number of important disease states.

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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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Deepak Srivastava, M.D.

Srivastava

Research Interests:
Developmental biology, pediatric cardiology, congenital heart defects, organogenesis, human genetics, stem cells, cardiac repair

Summary:
Dr. Srivastava’s work focuses on understanding cardiac development by elucidating the molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac cell fate and subsequently fashion a functioning heart. This foundation has been used to discover the genetic basis for some congenital heart malformations.

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Matthew L Springer, Ph.D.

 

Matt 2016

Research Interests:
Angiogenesis, VEGF, stem cells, progenitor cells, gene therapy, heart failure, myocardial infarction, coronary artery disease, cardiac regeneration, peripheral artery disease, vascular injury, nitric oxide, flavanols, skeletal muscle myoblasts, secondhand smoke

Summary:
Our research interests include cell therapy and gene therapy approaches to studying cardiovascular disease, with the goals of exploring potential treatments and understanding underlying mechanisms involved in angiogenesis, vascular function, and treatments for myocardial infarction. The laboratory is studying the effects of VEGF and pleiotrophin gene therapy on the heart and limb vasculature in mice. Further interests center in the therapeutic effects of ultrasound-guided bone marrow cell implantation into the heart after myocardial infarction, with a special emphasis on the therapeutic implications of the age and cardiac disease state of the cell donor. Similarly, the lab is studying the effects of age and disease on circulating angiogenic cells (sometimes called endothelial progenitor cells), with a focus on the roles of endothelial nitric oxide synthase and nitric oxide in the function of these cells. Lastly, they have developed a rat model of endothelium-dependent flow-mediated vasodilation, and are using it to examine mechanisms underlying vascular reactivity and how they are affected by cigarette smoke exposure.

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