Iva Greenwald

Greenwald Lab Website

National Academy of Sciences Member

American Academy of Arts & Sciences Member

Cell-cell interactions, signal transduction, and cell fate specification in C. elegans

We study cell-cell interactions, signal transduction, and cell fate specification during C. elegans development.  Much of our work is centered on LIN-12/Notch, the receptor component of a major signaling system for specifying cell fate during animal development.  In addition, mutations in core components and modulators of the LIN-12/Notch pathway have been implicated in cancer, Alzheimer's disease, and other diseases and syndromes. Using C. elegans, we study how LIN-12/Notch signaling is modulated during normal development and identify potential ways it may be modulated to combat disease.

In our developmental studies, we aim to understand the fundamental logic and molecular events that govern cell fate decision-making. We mainly study two simple cell fate decision paradigms in which LIN-12/Notch signaling is essential: the “AC/VU decision” and “VPC fate specification.” These simple paradigms offer the opportunity to apply powerful methods of genetic analysis to fundamental mechanisms of cell fate specification that operate in all animals.  During these events, different modulatory mechanisms regulate LIN-12/Notch activity and different signaling inputs are integrated so that correct cell fate decisions are made.   

We also use sensitive and specific suppressor and enhancer screens in C. elegans for “gene discovery”, with the aim of identifying new, conserved modulators of LIN-12/Notch and other signaling pathways. 

• de la Cova, C. and Greenwald, I. (2012) SEL-10/Fbw7-dependent negative feedback regulation of LIN-45/Braf signaling in C. elegans via a conserved phosphodegron   Genes Dev 26, 2524-2535. 
• Karp, X. and Greenwald, I.  (2013) Control of cell fate plasticity and maintenance of multipotency by DAF-16/FoxO in quiescent C. elegans.Proc Natl Acad Sci (USA) 110, 2181-2186.
• Sallee, M.D. and Greenwald, I. (2015) Dimerization-driven degradation of C. elegans and human E proteins.  Genes Dev 29, 1356-1361.