Department: Developmental Biology

Our laboratory investigates how complex, elaborately patterned tissues form during vertebrate embryonic development. In particular we aim to add a new dimension to our understanding of how cells “know” where to go, when to move, and differentiate. We combine classical embryology with state-of-the-art biochemistry, imaging, and genomics. Major research areas include delineating the translational regulatory code of the mammalian genome and cutting-edge imaging of tissue patterning.

Our lab is interested in the neuronal-glial interactions that underlie the development and function of the mammlian central nervous system.

Function of Hedgehog proteins and other extracellular signals in morphogenesis (pattern formation), in injury repair and regeneration (pattern maintenance). We study how the distribution of such signals is regulated in tissues, how cells perceive and respond to distinct concentrations of signals, and how such signaling pathways arose in evolution. We also study the normal roles of such signals in stem-cell physiology and their abnormal roles in the formation and expansion of cancer stem cells.

Dr. Bejerano, co-discoverer of ultraconserved elements, studies the Human Genome. Through computation and experimentation we investigate the Systems Biology parts-list of many thousands genomic regions involved in gene transcription regulation during embryonic development. Major interests include (1) the origins and evolution of these regions, (2) how they encode their individual as well as combined roles, (3) their contribute to human disease, and (4) their contribute to species adaptation.

Mammalian Evolution, Transcriptional Regulation, Placenta Morphology, Microbiota

The discovery that insulin-producing β-cells can be generated from cell sources within and outside the pancreas is of fundamental importance in terms of developing novel treatment strategies for diabetes. A major caveat to this is our relatively poor understanding of the players involved in this process and the lack of molecular characterization of the ‘converted’ β-cells. This knowledge is key to our success in enhancing this process to its maximum therapeutic potential and efficiency. In this..

Our laboratory combines synthetic chemistry and developmental biology to investigate the molecular events that regulate embryonic patterning, tissue regeneration, and tumorigenesis. We are currently using genetic and small-molecule approaches to study the molecular mechanisms of Hedgehog signaling, and we are developing chemical technologies to perturb and observe the genetic programs that underlie vertebrate development.

Chromatin regulation and its roles in human cancer and the development of the nervous system. Engineering new methods for studying and controlling chromatin in living cells.

Regulation of stem cell division and self-renewal Cell type specific transcription machinery and regulation of cell differentiation Developmental regulation of cell cycle progression during male meiosis Molecular dissection of the mechanism of cytokinesis.

I am interested in how the Hedgehog signaling transduction is regulated, and how the mis-regulation of Hedgehog pathway leads to human diseases such as Medulloblastoma.

Survival in changing environments requires the acquisition of new heritable traits. However, mechanisms that safeguard the fidelity of DNA replication often limit the source of such novelty to relatively modest changes in the genetic code. Thus, the acquisition of new forms and functions is thought to be driven by rare variants that occur at random, and are enriched during times of stress. We have begun to study an intriguing alternative hypothesis: that intrinsic links between protein folding ..

Mechanisms of Aging in C. elegans and humans.

We study the genetics of pancreatic islet cell differentiation using molecular, embryologic and genetic methods in several model systems, including mice, embryonic stem cells, and Drosophila. Our work suggests that critical factors required for islet development are also needed to maintain essential functions of the mature islet. Our knowledge of genetic and cellular pathways governing islet formation has allowed us to use stem cell lines to produce islet replacements in vitro.

My laboratory uses mice, stickleback fish, and humans to study the molecular basis of vertebrate evolution. Using genetics and genomics, we have tracked down key genes and mutations that control skeletal development, limb patterning, brain size evolution, skin color, salt handling, and susceptibility to arthritis and skin cancer. Many of these genetic mechanisms are used repeatedly, providing new insights into the molecular basis of evolution in many different species, including ourselves.

My research aims to understand how chromosomes interact to maintain genomic integrity and promote proper chromosome segregation. Recombination between chromosomes is required to generate genetic variation, maintain genome integrity through the repair of DNA breaks, and ensure proper chromosome segregation during meiosis, the specialized cell division program by which diploid organisms generate haploid gametes. Perturbations in recombination events can compromise these basic cellular functions..

Studying design principles of Caulobacter crescentus cell-cycle circuit by introducing genetic modifications into the circuit and applying live-cell time-lapse microscopy to track dynamics of fluorescently-labeled master cell-cycle regulators

Experimental and theoretical analysis and modeling of genetic regulatory circuits, particularly bacterial regulation and with emphasis on global regulation of Caulobacter crescentus. Bioinformatic analysis of bacterial genomes, of microarray expression patterns, and cross-species genomic analysis. Techniques: gene expression microarrays, fluorescent microscopy, electron microscopy, genetics, molecular biology

Our laboratory studies Wnt signaling in development and disease. We found recently that Wnt proteins are unusual growth factors, because they are lipid-modified. We discovered that Wnt proteins promote the proliferation of stem cells of various origins. Current work is directed at understanding the function of the lipid on the Wnt, using Wnt proteins as factors the expand stem cells and on understanding Wnt signaling during repair and regeneration after tissue injury.

Stem cells are unique in that can renew themselves through cell division or differentiate into a diverse range of specialized cell types. I will study genes that functions to prevent the growth of tumors and regulates stem cell decisions. Understanding the molecular mechanisms that mediate the choice between self-renewal and differentiation in stem cells has important implications for many areas of biology, including ancer treatment, regenerative medicine and new cell-based therapies.

Early Human Developmental Biology: From Egg to Embryo Organogenesis: Pattern formation Sex Determination in Embryogenesis

Our research is focused on the genetic regulation of animal development and its relation to birth defects, cancer, and neurodegeneration. We study mechanisms and functions of Hedgehog (Hh) signaling, which controls cell fates and growth, in the context of normal development and brain cancer. We study a neurodegenerative disease, Niemann-Pick C syndrome, that affects intracellular organelle movements and sterol homeostasis.

A basic question in developmental biology involves the mechanisms used to generate the three-dimensional organization of a cell from a one-dimensional genetic code. Our goal is to define these mechanisms using both molecular genetics and biochemistry.

We use genetic and cellular approaches to investigate the molecular basis of glial development and myelination in the zebrafish.

Mechanisms underlying homologous chromosome pairing, DNA recombination and chromosome remodeling during meiosis, using the nematode Caenorhabditis elegans as an experimental system. High-resolution 3-D imaging of dynamic reorganization of chromosome architecture. Role of protease inhibitors in regulating sperm activation.

Stem cell and cancer stem cell biology; development of T and B lymphocytes; cell-surface receptors for oncornaviruses in leukemia. Hematopoietic stem cells; Lymphocyte homing, lymphoma invasiveness and metastasis.

Research in our lab focuses on mechanisms of epigenetic regulation in differentiation and development. In particular, we are studying the function of histone modifying enzymes in embryonic stem cell self-renewal and in early cell fate decisions. We are interested in the role of chromatin modifications in establishment and maintenance of gene expression patterns during normal and pathological development, and in nuclear reprogramming.