E. Jane Albert Hubbard, PhD
Associate Professor of Pathology
Ph.D., 1993 Columbia University
Skirball Institute of Biomolecular Medicine
New York University School of Medicine
540 First Ave. 4th floor
New York, NY 10016
Office Tel: (212) 263-7154
Lab Tel: (212) 263-7533
[Preferred method of contact: e-mail]
Lab Website: http://saturn.med.nyu.edu/research/dg/jhubbardlab/
Research Theme(s):Meiosis, Morphogenesis, Pattern Formation, Signal Transduction, Stem Cell Biology, Growth Control
Keywords: C. elegans, Notch, Insulin, Cell Proliferation, Germ Line
My lab studies the developmental and physiological control of progenitor/stem cell proliferation and differentiation using the C. elegans germ line as a model system.
During the development and maintenance of tissues and organs, cells must decide whether, when, where and how much to proliferate. Improper control of cell proliferation can lead to stem cell failure, developmental defects and cancer. We focus on the relatively unexplored area of the control of pattern and extent of germline proliferation as a model for this process. In particular, we are interested in signaling between the soma and germ line that influences germline proliferation and differentiation during their co-development.
We began these studies with the analysis of C. elegans mutations that cause germline tumors and have uncovered the key anatomical and molecular events that underlie tumor formation in these mutants. These tumors result from a delay in the initial onset of differentiation during germline development. This delay causes an appropriate cell-cell contact between particular somatically derived gonad cells and undifferentiated (mitotically competent) germ cells. We use our detailed knowledge of proximal germline tumor formation to design and carry out large-scale genetic screens – both classical and RNAi-based screens – designed to identify genes that influence tumor formation. These approaches have identified candidate genes including genes involved in the insulin signaling pathway.
C. elegans germ cells are a powerful model for studying stem cells. The germ line contains a self-renewing or progenitor/stem cell population. A large body of work implicates a Notch receptorsignaling pathway to maintain germline mitotic fate in response to signals from the niche, the distal tip cell. The anatomy of this system is simple and accessible, and the genetic power of C. elegans offers great potential for furthering our understanding of niche-stem cell interactions in general. However, the spatial and temporal dynamics of germ cell division within the mitotic zone are not well defined. We are actively pursuing methods to better characterize these dynamics including ways to label putative germline stem cells, so as to follow their division patterns in live animals. We have pioneered a wet/dry statistical approach to investigate the dynamics of cell division in the proliferation zone. Our studies led to the unexpected result that cell division frequency is lower in cells that directly contact the distal tip cell, consistent with a model for a niche/stem cell/transit-amplifying cell system similar to mammalian stem cell systems such as the gut crypts.
Finally, in collaboration with computer science groups we are perusing computational modeling methods that can be applied to stem/developmental biology.
Research is supported by the National Institutes of Health, the New York State Stem Cell Foundation
Selected Publications (2006-2010):
- Soma-germline interactions that influence germline proliferation in C. elegans. D.Z. Korta, E.J.A. Hubbard, 2010 Developmental Dynamics 239:1449–1459 (peer-reviewed review article). PMID: 20225254
- Insulin signaling promotes germline proliferation in C. elegans. D. Michaelson, D.Z. Korta, Y. Capua, E.J.A. Hubbard, 2010. Development 137(4):671-80. PMID: 20110332
- A “latent niche” mechanism for tumor initiation. M. McGovern, R. Voutev, J. Maciejowski, A. Corsi, E.J.A. Hubbard (2009). Proc. Natl. Acad. Sci. USA 106:11617-22. PMID: 19564624
- MSP and GLP-1/Notch signaling coordinately regulate actomyosin-dependent cytoplasmic streaming and oocyte growth in C. elegans S. Nadarajan, J.A. Govindan, M. McGovern, E.J.A.Hubbard, D. Greenstein, 2009. Development 136:2223-2234. PMID: 19502484
- Characterization of the C. elegans Islet LIM-homeodomain ortholog, lim-7. R. Voutev, R. Keating, E.J.A. Hubbard, L.G. Vallier, 2009. FEBS Letters 583:456-464. PMID: 19116151
- A scenario-based approach to modeling development: A Prototype Model of C. elegans Vulval Cell Fate Specification. N. Kam, H. Kugler, R. Marelly, L. Appleby, J. Fisher, A. Pnueli, D. Harel, M.J. Stern, E.J.A Hubbard. Developmental Biology 323:1-5. PMID: 18706404
- A “FLP-out” system for controlled gene expression in C. elegans. R. Voutev, and E. J. A. Hubbard. Genetics 180:103-119. PMID: 18723890
- Towards Verified Biological Models. A. Sadot, J. Fisher, D. Barak, Y. Admanit, M.J. Stern, E.J.A. Hubbard, and D. Harel (2008) IEEE/ACM Trans Comput Biol BioinformApr-Jun;5(2):223-34 [featured cover article] PMID: 18451431
- The C. elegans germ line: a model for stem cell biology. E. J. A. Hubbard (2007) Developmental Dynamics 236:3343-3357. PMID:17948315
- Quantitative analysis of germline mitosis in adult C. elegans. J. Maciejowski, N. Ugel, B. Mishra, M. Isopi, E.J.A. Hubbard (2006) Developmental Biology 292:142-151. PMID: 16480707
- Alterations in ribosome biogenesis cause specific defects in C. elegans hermaphrodite gonadogenesis. R. Voutev, D.J. Killian, J.H. Ahn, and E.J.A. Hubbard (2006) Developmental Biology 298:45-58. PMID: 16876152