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Laboratory of Cellular and Developmental Biology

Photo of Jurrien Dean Jurrien Dean, M.D.

Chief

jurrien.dean@nih.gov
Investigating molecular mechanisms of cell differentiation and development to understand normal biology and provide insight into human disease.
About the Lab

Lab Sections & Chiefs

Developmental Genomics Section

Brian Oliver, Ph.D., Section Chief

The Developmental Genomics Section strives to understand how complex genotypes and environmental interactions result in disease. Researchers in the section use the fruit fly, Drosophila melanogaster, as a model system. The section’s long-term goal is to develop predictive models of gene function based on gene network analysis in fruit flies. In this work, it is important to identify all the genes, mRNA isoforms, and regulatory elements encoded in the genome. It is also important to determine genetic function across the genome and to develop connectivity maps. Our approach relies on a combination of high-throughput techniques to profile biological processes—such as expression, promoter occupancy, and chromatin status—in conjunction with computational analysis of genomic sequence. The section’s work also addresses a number of interesting questions highly amenable to genome-wide analysis. For example, we are studying lipid storage and the transcriptional response to altered gene copy number.

Gene Regulation and Development Section

Ann Dean, Ph.D., Section Chief

The Gene Regulation and Development Section studies how enhancers activate transcription. Research focuses on the mouse and human beta-globin gene families that are regulated in a tissue and developmental-stage-specific fashion by a complex enhancer, the locus control region (LCR). We use biochemical, genetic, genomic, and computational approaches in cell lines, embryonic stem cells, and mice to (1) identify proteins involved in chromatin looping between the LCR and globin genes, (2) investigate the role of long non-coding RNAs in LCR function, and (3) determine how chromosome folding influences enhancers. The studies contribute to gene therapy efforts by revealing the complex interplay between genes and their modulators in the nucleus.

Mammalian Developmental Biology Section

Jurrien Dean, M.D., Section Chief

The Mammalian Developmental Biology Section investigates female gonadogenesis and early embryogenesis. Research emphasizes events that define the maternal to embryonic transition in mammals by developing models and testing their predictions with mouse transgenesis. One investigative focus is on genetic hierarchies that control follicle formation and expression of maternal effect genes within the ovary. Another is on the molecular basis of sperm-egg recognition that results in fertilization and the intricately orchestrated events that effectively prevent polyspermy. Lastly, we investigate the role of maternal gene products in the activation of the embryonic genome progression through cleavage-stage development and establishment of initial embryonic cell lineages.

Molecular Mechanisms of Development Section

Alan R. Kimmel, Ph.D., Section Chief

The Molecular Mechanisms of Development Section investigates molecular processes required for establishing a terminally differentiated organism from a homogeneous population of totipotent cells. Work in the section focuses on receptor-mediated signal transduction pathways, as well as nuclear targets to identify mechanisms that specify multicellular differentiation, developmental cell fate, and pattern formation. Approaches include genetic screens, cell imaging, biochemical assay, and deep sequencing with computational analyses. Recent data have defined novel regulatory pathways for mTOR, tyrosine kinase, and presenilin signaling, and demonstrated an essential role for gene-specific chromatin remodeling for developmental induction.

Nuclear Organization and Gene Expression Section

Elissa Lei, Ph.D., Section Chief

The Lei laboratory seeks to understand how higher-order chromatin structure influences gene expression. Our main goal is to elucidate mechanisms and regulation of chromatin insulators, which are DNA-protein complexes situated throughout the genome that define distinct transcriptional domains. One area of particular interest is the contribution of RNA and RNA-related mechanisms to chromatin organization. Approaches used in the laboratory include genetics, biochemistry, cell biology, molecular biology, and computational analysis of genome-wide datasets. Our work promotes understanding of the intricately orchestrated transcriptional programs needed for proper development and differentiation.

Section of Regulatory RNAs

Katherine McJunkin, Ph.D., Stadtman Tenure-Track Investigator, Acting Section Chief

Research in the McJunkin lab has two major long-term goals: 1) to define the biological functions of miRNAs during embryogenesis and 2) to elucidate mechanisms of miRNA turnover. Using C. elegans as a model organism to address these questions, we combine the strengths of classical forward genetics with CRISPR-Cas-9-mediated genome editing, next-generation sequencing, cell biology, and biochemical techniques. Because embryonically-expressed miRNAs exhibit a sharp decrease in abundance at the end of embryogenesis, our efforts to simultaneously study the biology of these miRNAs and the mechanisms of miRNA decay has the potential to uncover regulatory modules that couple miRNA decay to developmental timing.