Kavita Arora, Ph.D.
Drosophila development - We are interested in understanding the role of two TGF-ß related genes, screw (scw) and decapentaplegic (dpp), in specifying cell fate during embryonic development in the fruitfly Drosoila. Since the TGF-ß signaling pathway is evolutionarily conserved, findings from a genetically tractable organisms like Drosophila can provide insights into the mechanism of action of TGF-ß proteins in other organisms, including humans. We have cloned the scw gene and shown that although scw transcripts are ubiquitously expressed, the protein is only required in dorsal cells. It is likely that Scw may be activated in a subset of the cells where it is expressed because of its interaction with other genes involved in patterning the embryo. We are using molecular genetic ...

Lee Bardwell, Ph.D.
Cell Signaling - We use the techniques of molecular biology, biochemistry, genetics and cell biology to study fundamental questions of cell signaling and regulation: (1) Conserved signaling pathways controlling growth and development in yeast and mammalian cells. (2) Mechanisms of specificity in signal transduction, especially protein kinase signaling. (3) Regulation of mitogen-activated protein kinase (MAPK) cascades in yeast and mammalian cells. (4) Protein-protein interactions and their role in signaling. Signal transduction networks are a crucial part of the circuitry by which a cell regulates and coordinates its growth and developmental program, and its response to the external environment. Faulty or malfunctioning signaling pathways lie at the heart of the molecular pathology of many diseases, including cancer. The signaling components we study have been highly conserved through ...

Bruce Blumberg, Ph.D.
Hormonal signaling; Functional genomics - Researchers in the Blumberg laboratory study a family of ligand-modulated transcription factors, the nuclear hormone receptors, and their role in development, physiology and disease. Two receptors are particularly relevant to cancer – the retinoic acid receptors, RARs, and the steroid and xenobiotic receptor, SXR. One long-standing interest in the laboratory concerns the interactions between nuclear receptor and growth factor signaling in important developmental patterning processes. Retinoic acid (RA) and fibroblast growth factors (FGFs) are critical factors that interact to mediate a variety of developmental processes. RA and FGF pathways are mutually inhibitory and this inhibition is important for key developmental ...

Hans Bode, Ph.D.
Pattern formation in hydra and the evolution of developmental mechanisms - Evidence is rapidly accumulating that the same genes are used by different organisms to regulate similar developmental processes. This raises the issue of the evolution of developmental mechanisms. Which mechanisms arose early and were conserved through evolution, and which arose later? Since cnidarians, of which hydra is a member, arose very early in metazoan evolution, the organism is strategically placed to examine this issue. Further, the processes governing pattern formation and cell fate determination are well understood in hydra at a tissue and cellular level. Because the body plan is simple, the patterning processes are ...

Susan V. Bryant, Ph.D.
Limb development and regeneration - How to Regenerate a New Leg: What we can learn from salamanders - Alone among vertebrates, urodele amphibians are able to regenerate lost body parts as adults. The key to this ability is that limb cells are triggered to dedifferentiate and reinitiate growth and pattern formation. Our strategy is to use axolotls (Ambystoma mexicanum) to discover the signals that trigger the regeneration response, in the belief that these signals have enormous potential and consequences for human health. Our long term goals are to identify the regeneration-enabling signals in limbs, in order to support progress towards the eventual application of these molecules to the improvement of human repair mechanisms. In current research, we are using assays derived from ...

Anne Calof, Ph.D.
Neurogenesis and Neuronal Differentiation - My laboratory’s research efforts are concentrated on two main topics: (1) understanding the nature and the targets of the signals that regulate the production of neurons by neuronal stem and progenitor cells during development and regeneration of the nervous system; and (2) understanding the molecular etiology of human genetic diseases that affect growth and development, especially of the nervous system. To understand these questions, we study the basic biology of stem cells, but we also employ mouse genetics, molecular biology, tissue culture, and computational approaches. Our goal is to understand how key genes regulate organ system growth and patterning, and how key signaling molecules regulate stem and progenitor cell numbers in the stem cell niches ...

Ken Cho, Ph.D.
Developmental Regulation by TGF-b Member Growth Factors - Bone Morphogenetic Proteins (BMPs) are key players in a multitude of cell signaling events, from the subdivision of tissue types during early embryogenesis to the formation of limbs and internal organs. We have identified a conserved BMP responsive element (BRE) within the promoter of Xvent2 and Id3 in Xenopus and found that the BRE is conserved in fly, fish, mice and humans. A key molecule mediating the signaling is the evolutionally conserved, multi-zinc finger transcription factor Schnurri (Shn), which has the ability to function as a transcriptional activator or repressor depending on the biological context. Since Shn functions as an evolutionarily conserved transcriptional factor involved in BMP signaling ...

Peter Donovan, Ph.D.
Molecular Genetics of Germ Cell and Stem Cell Development - Our laboratory is interested in four critical aspects germ cell and stem cell biology. One aspect is the regulation of developmental potency within the mammalian germline and within pluripotent stem cells derived from germ cells (embryonic germ cells, or EG cells) and from early embryos (embryonic stem cells, or ES cells). Learning how to control stem cell potency may point to new methods of maintaining EG or ES cells in an undifferentiated state for a prolonged period of time, or avoid the tumorigenic potential of these cells when transplanted into animals. A second major area of research is aimed at understanding the factors ...

Aimee Edinger, VMD, Ph.D.
Apoptosis, cancer, intracellular trafficking - The Edinger Lab studies how cell growth and survival is regulated by growth factors at the level of nutrient transporter expression. This research has important implications for cancer biology and treatment. What are growth factors and why should we study them? Unicellular organisms such as yeast grow and divide in response the level of extracellular nutrients available: a yeast cell placed in the midst of abundant nutrients will rapidly proliferate (see right). When these nutrients are exhausted, the yeast cells will sporulate or die. Following the evolutionary transition from unicellular to multicellular organisms, this nutrient-limited style of cell growth could no longer be sustained. The cells of multicellular organisms are constantly bathed in nutrients ...

Steven Gross, Ph.D.
Laser tweezers; Regulation of molecular motors - My research is quite cross-disciplinary. The majority of biological studies have focused on biochemical or genetic understanding of biological processes, however understanding the relevant physical processes is also important. Proteins physically do things, and to understand the biology, we must start to think about proteins as machines, as well as considering their biochemical properties and genetic regulation. We will soon know the Human Genome, we already know the Drosophila and the C. Elegans Genomes, and yet are very far from understanding how proteins work, and how the exquisitely ordered structures we observe in cells, embryos, and developed organisms come about. ...

Taosheng Huang, M.D., Ph.D.
Molecular basis of genetic diseases in human - The primary interest of my lab is to study the molecular basis of genetic syndromes and to apply the discoveries from rare diseases to common conditions. Currently, we are focusing on the following areas:

The role of TBX3 in breast cancer TBX3 is a T-box transcription factor. Mutation of TBX3 causes Ulnar-Mammary syndrome, which is characterized by hypoplasia and absence of the mammary gland. We were one of the first groups to show that overexpression of TBX3 plays an important role in breast cancer. We have analyzed TBX3 expression in human breast cancer tissue. The TBX3 expression levels were compared with those ...

Arthur D. Lander, M.D., Ph.D.
Signaling & morphogenesis - The Lander lab is interested in the molecular mechanisms by which cells communicate. We focus on two kinds of pathways–those involving growth factors and their receptors, and those involving molecules of the extracellular matrix and their receptors. We study these pathways in the context of both mammalian (mouse) development and cancer biology, since growth control and cell-matrix interactions are critical to both processes. We also focus on cells of the nervous system, to understand why the growth that occurs during developing often fails to recur after injury (e.g. spinal cord injury). We are able to work in such a wide range of areas by (1) emphasizing fundamental aspects of cellular communication that have broad applications, and (2) utilizing approaches such as transgenic ...

Eva Lee, Ph.D.
Cell cycle and molecular genetics studies of breast cancer - Eva Lee and her laboratory continue to conduct investigations on tissue-specific functions of breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, and interactions between tumor suppressors and endocrines. Dr. Lee's group demonstrated that inhibition of the stabilized progesterone receptor in BRCA1 and p53-mutated mammary epithelial cells prevented or delayed mammary tumors. Her team has continued to focus on the mechanisms of progesterone receptor stabilization as well as the usage of anti-progesterone in breast cancer prevention and progesterone receptor positive breast cancer treatment. How mutations of BRCA genes affect mammary epithelial cell fates ...

Ulrike Luderer, M.D., Ph.D.
Reproductive toxicology, developmental toxicology - Research in my laboratory centers on the mechanisms by which chemical toxicants damage the ovary, potentially causing infertility and ovarian cancer, and in understanding differences in ovarian susceptibility to toxicants. We are particularly interested in oxidative stress as a mechanism of ovarian injury and in the modulation of susceptibility to ovarian injury by biotransformation enzymes and antioxidants. Many known ovarian toxicants are conjugated by the tripeptide glutathione (GSH), and GSH is also a critical detoxification mechanism for reactive oxygen species. Work in my laboratory has demonstrated roles for oxidative stress in mediating both spontaneous and toxicant-induced apoptosis in granulosa cells of ovarian follicles ...

Grant MacGregor, Ph.D.
Analysis of Mammalian Gametogenesis - Gametogenesis involves production of male and female germ cells required for maintenance of a species. In addition to its inherent interest, study of gametogenesis is also useful to investigate a wide range of important cell biology processes found in most organs including cell-cell communication, stem cell biology, meiosis, cellular differentiation and cellular adhesion. Gametogenesis is also important from an applied research perspective as approximately 15% of couples are infertile. New information about the gene products required for gametogenesis could be applied to diagnosis and treatment of infertility. In addition, such information may ...

Ronald Meyer, Ph.D.
Neural injury regeneration - Our primary interest is in CNS nerve injury and repair. We are exploring this issue using the visual system. When the optic nerve of a mouse or any other mammal is severed, the nerve fails to regenerate and the animals are permanently blind. However, in goldfish, the severed nerve will regrow back to the brain to restore orderly nerve connections and vision. Much of our current work is focused on understanding how the optic nerve responds to injury and how the neurons in the brain respond to the loss of their nerve connection in the goldfish. In vivo imaging technology using widefield and 2 photon microscopy is used to observe the injured and regenerating axons in the living brain so as to understand the dynamics of their behavior and response to treatments. Electrophysiological ...

Edwin Monuki, M.D., Ph.D.
Cerebral cortex development, disease and evolution - Neural Stem Cell Fate and Border Control in the Developing Forebrain - During mammalian forebrain development, neural stem cells (NSCs) adopt a number of unique cell fates. Two of these are the choroid plexus, the source of cerebrospinal fluid (CSF), and the cerebral cortex, the seat of our higher cognitive and neurologic functions. The mechanisms used to make cortical and choroid plexus cells and their borders remain fundamental questions in neuroscience. Moreover, when these structures form improperly, common disorders such as hydrocephalus, mental retardation, and epilepsy too often ensue. The goal of our lab is to understand how these forebrain cell types are formed and separated, then apply this ...

Diane O’Dowd, Ph.D.
Sypnatic plasticity; Excitability - For the past 20 years my research lab at UCI has studied the activity of living neurons from the brains of both flies and mice. Using molecular genetic manipulations and whole cell electrophysiology we are exploring the role of specific genes in regulating functional plasticity of developing and mature neural circuits. We are also examining how environmental factors such as exposure to specific drugs, including nicotine, can influence information transfer between neurons. A basic understanding of the genes and environmental factors that influence information processing between small groups of neurons is key to development of drugs and gene therapies aimed at restoring normal activity in the human brain ...

Maike Sander, M.D.
Pancreas organogenesis and regeneration in mice - Our laboratory studies the molecular mechanisms that underlie cell differentiation and cell regeneration in the developing and adult pancreas. Using mouse genetic approaches, we have investigated which molecules control the switch between maintaining pancreatic stem/progenitor cells and inducing their differentiation into insulin-producing beta-cells. The mouse is an excellent model to study these questions, as it allows us to selectively activate and inactivate genes in a temporally and spatially controlled manner. The goal of our research is to identify molecular pathways that could be targeted to induce beta-cell regeneration or to develop a cell-based therapy for treatment of diabetes. ...

Thomas Schilling, Ph.D.
Zebrafish developmental genetics - Our laboratory uses genetics and molecular biology to study pattern formation in the early zebrafish embryo. The rapid development and simple anatomy of this teleost embryo, together with recently developed techniques for reverse genetics and a nearly complete genome sequence, make zebrafish a powerful molecular genetic system for studying the mechanisms of development. We focus on two areas: (i) neural crest specification and formation of the skeleton in the early embryo and (ii) long-range signals, morphogens, that pattern the anterior-posterior (A-P) axis of the nervous system. In both cases, we are interested in how gene functions translate into cell behaviours and the formation of tissues and organs. A major focus of the work in ...

Rahul Warrior, Ph.D.
Molecular genetic analysis of nuclear migration and growth factor signaling in Drosophila - We use Drosophila genetics, molecular and cellular techniques to study three mechanisms critical for normal development: (1) How extracellular proteoglycans (HSPGs) affect growth factor (especially BMP) signaling (2) How cells respond transcriptionally to Bone Morphogenetic Protein (BMP) ligands and (3) How a genetic pathway regulates the position and movement of the nucleus within a cell. The genes and pathways involved in these processes are evolutionarily conserved, and when disrupted in humans, cause congenital defects and disease ...