Nadeem Moghal, PhD

In humans, dysregulation of growth factor signaling is linked to developmental syndromes and many forms of cancer. We study regulation of signaling by the epidermal growth factor receptor (EGFR), an evolutionarily conserved receptor that is implicated in a wide number of human cancers. With many key components of the EGFR pathway defined, the greatest challenges lie in understanding the extensive regulatory inputs and how they are coordinated to achieve specific outputs. For these studies, we focus on genetic approaches in the nematode C. elegans, which allows us to identify regulatory mechanisms that operate in the context of a whole animal. Precise patterning of the nematode vulva requires multiple levels of regulation of EGFR signaling and involves cross-talk with Wnt signaling, another growth factor signaling pathway involved in human cancer. Small deviations from this regulation result in quantifiable changes in vulval patterning.

By studying vulval development, we have identified a number of new regulatory mechanisms. Current work is aimed at studying how neuromuscular activity controls the response of vulval progenitor cells to growth factors and determining how a specific receptor protein tyrosine phosphatase regulates EGFR signaling. In addition, we have isolated a number of mutations that cause excessive responses to growth factor signaling, whose molecular identities we are trying to determine.