Assistant Professor of Genetics

* B.S. University of Illinois, 1990
* Ph.D. University of Texas (Houston), 1996

Research Interests:

* Functional genomic analysis of global gene expression mechanisms
* C. elegans germline development

My laboratory uses whole-genome functional genomics approaches to study how underlying gene expression programs regulate the development of an animal.

Current Research:

We focus on the development of a single tissue, the germline, in the model organism C. elegans. This small nematode provides two key advantages: an excellent genetic system for understanding how cell fate is specified, and a completely sequenced and well-annotated genome. We use functional genomics tools to dissect the molecular mechanisms governing germ cell maintenance and differentiation in the model organism C. elegans.  Conserved regulatory pathways, such as the Notch, Ras, and Retinoblastoma pathways, act to control proliferation and differentiation in these cells.  The developing C. elegans germline requires tight spatial and temporal control of gene activity for proper formation. Epigenetic control of gene expression plays an important role in governing germ cell fate through the post-translational modification of histones and by RNAi-mediated post-transcriptional control.  Projects in the lab investigate the mechanisms controlling germ cell specification in the early embryo, as well as the regulatory hierarchy controlling germline stem cells before and after differentiation into functional gametes.

Current Projects:

Germline stem cells.  Virtually all cells in C. elegans are born within a determinate lineage.  The single exception is a pair of primordial germ cells, which divide an unspecified number of times to populate the gonad.   These proliferative germ cells bear several hallmarks of stem cells:  they require a niche in the distal end of the gonad for maintenance, they self-renew, and they retain totipotency, since they can generate every cell type of the subsequent generation.  Their maintenance also requires Notch signaling.  We have used a functional genomics approach to investigate the properties of germline stem cells in C. elegans, and identified a large set of genes expressed primarily in germline stem cells. Many of these genes encode proteins predicted to function in chromatin-binding and transcriptional regulation, in RNA binding and RNA regulation, and as stress-activated chaperones. Efforts are underway in the lab to analyze the function of these genes in germline stem cell proliferation.

Germ cell-specific organelles.  In C. elegans, the germ line is set aside within the first few embryonic divisions.  As each cell in the embryonic P lineage divides, it produces another P cell that retains germ cell characteristics, and a somatic cell that does not.  Within four divisions, the P lineage is completely segregated from all somatic lineages.  One feature that distinguishes germ cells from somatic cells is the presence of unique cytoplasmic, RNA-rich, granular organelles, whose exact function remains mysterious.  In C. elegans, these organelles, called P granules, are provided maternally and segregate with the P lineage during the initial embryonic divisions.  All germ cells born from the P lineage contain P granules (except mature sperm).  Several protein components of P granules have been identified, but their contribution to P granule function and germline viability remains unclear.  We have identified two novel, related proteins that localize exclusively to embyonic P granules.  They are not found in other cell compartments or on P granules in larvae or adults.  These genes are called meg-1 and meg-2 (maternal-effect germ cell-defective), and they are required for larval germ cell proliferation and normal P granule morphology.  meg-1 has genetic interactions with core components of P granules that suggests that meg-1 and meg-2 are required to regulate certain aspects of P granule function in the early P blastomeres during the time that somatic and germ fates are intermingled. Current efforts in the lab are directed toward defining the exact function of MEG-1 and MEG-2 and dissecting how P granules affect transcript stability in the early embryo.