Category: Developmental Biology and Congenital Anomalies


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.

UCSF Profiles Page: 


Christina Theodoris, M.D., Ph.D.

Research Interests:

Gene regulatory networks, machine learning, and cardiovascular disease

Summary:

Our lab studies how genes interact within networks to direct normal heart development and how those networks are disrupted in cardiovascular disease. Using a combination of computational and experimental approaches, we map the disrupted gene networks to enable the design of therapies that correct them back to the healthy state.

UCSF Profiles Page: 


Matthew L Kutys, Ph.D.

Research Interests:

Notch receptor signaling and chemo-mechanical regulation of vascular barrier, molecular regulation of endothelial cell morphodynamics during angiogenic sprouting and in cerebral small vessel disease, cardiac myocyte sarcomerogenesis, and angiocrine niche contribution to parenchymal tissue development, cancer, and infectious disease progression. 

Summary:

Research in the Kutys Lab is focused on achieving a molecular and physical understanding of biological mechanisms that interact across time and length scales to enable emergent, tissue morphogenic behaviors. Central to our efforts is the development and application of biomimetic microphysiological culture models,  organ-on-chip systems, that incorporate three-dimensional (3D) organotypic architectures and permit the study of human tissue development, regeneration, and pathogenesis with unprecedented resolution and biological control. Combining these models with innovative molecular technologies and high content microscopy, a major focus of my laboratory is understanding orchestration of tissue morphogenic behavior and cell fate specification by cell-cell and cell-extracellular matrix (ECM) adhesion complexes during cardiovascular development and disease.

Current projects in the lab focus on: Notch receptor signaling and chemo-mechanical regulation of vascular barrier, molecular regulation of endothelial cell morphodynamics during angiogenic sprouting and in cerebral small vessel disease, cardiac myocyte sarcomerogenesis, and angiocrine niche contribution to parenchymal tissue development, cancer, and infectious disease progression. 

UCSF Profiles Page:


Nevan J. Krogan, Ph.D.

Research Interests:
Systems biology, quantitative unbiased approaches, proteomics, genetic interactions, proteinprotein interactions, post-translational modifications, cancer, infectious diseases, cardiac development, psychiatric disorders.

Summary:

Our research focuses on fundamental biological mechanisms, because cures to many diseases have been revealed by unexpected discoveries in the basic sciences. We use and develop complementing technologies that allow the unbiased study of the cell. We create maps to study how proteins work together in cells, and how this changes during different diseases, including infectious diseases, cancer as well as neurological and psychiatric disorders. We strongly believe that impactful research is accomplished when diverse groups of scientists work together, and therefore we are working in close collaboration with national and international experts from different disciplines on all of our projects.

UCSF Profiles Page


Abigail Buchwalter Cool, Ph.D.

 

Research Interests:
We study the mechanisms that govern the specialization and maintenance of nuclear organization across cell types.

Summary:
We seek to understand how the organization of the cell nucleus is established, specialized across cell types, and maintained over time to influence cellular identity. “Nuclear organization” involves the non-random packaging of the genome within the nucleus, but also the assembly and interactions of other nuclear structures, such as the nuclear lamina and the nucleolus.

This work begins with a particular focus on the nuclear lamina, a nuclear structure that is essential for mammalian development and is mutated in ~15 “laminopathy” diseases that afflict the heart, muscle, bone, fat, and nervous system. We focus on three main thematic areas: (i) defining the essential roles that the nuclear lamina plays in nuclear organization, (ii) exploring disruption of nuclear organization as a possible cellular mechanism of aging, and (iii) determining how nuclear organization is maintained (or alternatively, remodeled) over time.

 

 

 


Vasanth Vedantham, M.D.

Research Interests: Development and function of the cardiac conduction system; molecular regulation of cardiac pacemaker cells; mechanisms of cardiac arrhythmias

 

Our lab is focused on cardiac pacemaker cells, specialized cardiomyocytes whose autonomous electrical activity allows the sinoatrial node to serve as the heart’s natural pacemaker. Specific questions include: How are pacemaker cells different from regular heart cells at the level of gene expression and regulation? How does their unique gene expression signature confer their distinctive electrophysiological properties? How have selection pressures generated functional differences in pacemaker cells among different vertebrate species? What are the molecular mechanisms that guide pacemaker cells to integrate electrically with the rest of the heart to form a node? How do pacemaker cell biology and function change in response to physiological and pathological stress? What is the mechanistic link between sinus node dysfunction and atrial fibrillation? Our approaches include mouse genetics, whole-animal and ex-vivo electrophysiology, cellular and molecular electrophysiology, gene expression analysis, and bioinformatics. Ultimately, we hope to design novel treatments for patients suffering from heart rhythm disorders, including sinus node dysfunction and atrial fibrillation

UCSF Profiles Page: 


David R Raleigh, M.D.

Research Interests: Hedgehog signaling, developmental biology, brain tumors and molecular therapeutics

 

More children die from brain tumors than any other type of cancer, and the most common type of brain tumor in children is medulloblastoma. Like all cancers, medulloblastoma is caused by uncontrolled cell growth. Approximately one-third of medulloblastoma cancers arise when a particular signal that tells brain cells to grow, called Hedgehog, gets stuck in the “on” position. We are interested in uncovering exactly how Hedgehog signals tell cancer cells to grow. To do so, we are investigating how the Hedgehog pathway is activated, and how Hedgehog activation regulates the expression of other signals to influence cell growth. Understanding how Hedgehog signals cause cancer may show us how to turn off these signals, and potentially, lead to new therapies for medulloblastoma.

UCSF Profiles Page: 


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.

UCSF Profiles Page


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.

UCSF Profiles Page


Xiaokun Shu, Ph.D.

Shu

Research Interests:
Protein Rational Design and Directed Evolution for Biology and Medicine

Summary:
We are developing technologies to bridge the gap between clinical medicine and molecular biology. Their successful use in biomedicine will significantly improve treatment of disease.

UCSF Profiles Page


Nelson B Schiller, M.D.

Schiller

Research Interests:
Dr. Schiller specializes in the use of echocardiography in the diagnosis and treatment of heart disease. His research interests center around the quantitation of left ventricular function by quantitative two-dimensional echocardiography and Doppler.

Summary:
Measuring the heart has been a preoccupation of civilizations since ancient Egypt. Measuring the heart using noninvasive techniques that are free of ionizing radiation has riveted the attention of modern medicine because knowledge of the size of the heart’s anatomic parts provides powerful diagnostic and therapeutic information. Dr. Nelson B. Schiller a member of the Department of Medicine, Cardiology Division, CVRI and John J. Sampson-Lucie Stern Endowed Chair in Cardiology, has spent his career investigating the application of echocardiography to the precise measurement and clinical application of the volume, weight and hemodynamics of the chambers and valves of the heart. His work is currently centered on the Heart and Soul Study (Mary Whooley, MD PI), where echocardiography measurements are being related to outcomes of heart disease.

UCSF Profiles Page


Jeremy F Reiter, M.D., Ph.D.

Reiter

Research Interests:
Signaling, primary cilium, stem cell, Hedgehog, Wnt

Summary:
In the process of development, a single egg cell develops into a complex organism. Understanding how that first cell generates such astonishing complexity is one of biology’s great tasks. Not only is this task fundamental to our understanding of ourselves, but it is also critical to understanding the causes of birth defects and other diseases. Many of the mechanisms underlying development depend on intercellular communication, the ability of cells to send and receive information. Secreted signaling proteins can communicate many different types of information, from what type of cell a cell should become to whether a cell should live or die. We are studying the mechanisms by which a cellular organelle, the primary cilium, receives and interprets these signals during development. We are also studying how mistakes in these signals contribute to diseases such as cancer.

UCSF Profiles Page