Iva  Greenwald
Iva Greenwald
Professor, Department of Biochemistry and Molecular Biophysics
Professor, Department of Genetics

Address: 701 West 168th Street Room 720A New York NY 10032
Phone: 212-305-6928
Fax: 212-1721


Education and Training:
Ph.D. 1982, M.I.T.
Postdoctoral Fellow 1983-1986, MRC Lab of Molecular Biology
bullet  Department of Biochemistry and Molecular Biophysics
bullet  Department of Genetics and Development
bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
bullet  Howard Hughes Medical Institute
Training Activities:
bullet  Department of Genetics and Development
bullet  Department of Biochemistry and Molecular Biophysics
bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
Research Summary:
(800 words, max)
Cell-cell interactions, signal transduction, and cell fate choice; genetic and molecular studies of C. elegans development.
Current Research:
One of the fundamental problems in developmental biology is how so many different cell types are generated from a one-cell zygote. It is known that cell-cell interactions play important roles in cell type specification during development. We study this process in the nematode C. elegans, which is extremely tractable to genetic and molecular manipulation. However, since the mechanisms and molecules involved in cell fate specification appear to be conserved in mammals, studies in simpler organisms such as C. elegans have direct application to higher animals.

Many projects in my laboratory involve the study of lin-12 gene. LIN-12 is the archetype of the LIN-12/Notch family of putative transmembrane proteins that is found throught the animal kingdom. In C. elegans, LIN-12 appears to function as a receptor during cell-cell interactions that specify cell fate. In mammals, genes related to lin-12 are important for normal development; furthermore, mutations in genes related to lin-12 have been associated with cancer in mice and people. Ultimately, we want to understand the molecular mechanism by which lin-12 and its relatives in higher organisms specify cell fates. We have adopted a number of stategies to achieve this goal. One strategy is a "genetics in reverse" approach. This strategy has included performing structure/function analyses of lin-12 and its ligands by using homologous and heterologous regulatory sequences to direct expression of mutant proteins in C. elegans. Another strategy is to identify other genes that influence lin-12 activity. We have identified a number of sel genes, which may interact directly or indirectly with lin-12, by mutations that suppress and/or enhance lin-12 mutations. In addition, we have screened directly for proteins that interact with defined regions of LIN-12 protein. A combination of genetic and molecular characterization of candidate genes is elucidating their role in lin-12-mediated cell signaling.

Our interest in one sel gene, sel-12, extends beyond its involvement in lin-12-mediated signaling. The SEL-12 protein is highly similar to human presenilins, which have been implicated in the development of Alzheimer's disease. The ability to bring the powerful tools of classical and molecular genetic studies in C.elegans can now be brought to bear on fundamental issues of the structure and function of the presenilins, using the same strategies as we have used for studying lin-12.

(6 max)
1. Yoo, A. S., and Greenwald, I. : (2005) LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans..  Science  310: 1330-1333

2. Shaye, D. D., and Greenwald, I.: (2005) LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans..  Development  132: 5081-5092

3. Myers, T. R., and Greenwald, I.: (2005) lin-35 Rb acts in the major hypodermis to oppose ras-mediated vulval induction in C. elegans. .  Developmental Cell  8: 117-123

4. Katic, I., Vallier, L. G., and Greenwald, I. : (2005) New positive regulators of lin-12 activity in Caenorhabditis elegans include the BRE-5/Brainiac glycosphingolipid biosynthesis enzyme. .  Genetics  171: 1605-1615

5. Jarriault, S., and Greenwald, I.: (2005) Evidence for functional redundancy between C. elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE..  Dev. Bio.  287: 1-10

6. Yu, H., Yoo, A. S., and Greenwald, I. : (2004) Cluster Analyzer for Transcription Sites (CATS): a C++-based program for identifying clustered transcription factor binding sites..  Bioinformatics   20: 1198-1200

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