Leah Wolfsberg

Background & Contact Information

Post-Baccalaureate Research Assistant (Aug 2023 – present)
Education: B.S in Biochemistry from Colorado State University
Email: leahwolf@ad.unc.edu

 

 

 

 

 

Research Information

Epithelial cells rely on dynamic cell shape changes to multiply, differentiate, and create a body’s architecture. This is achieved in part via connections between the actomyosin cytoskeleton with cell-cell adherens junctions (AJs). The AJ-cytoskeletal linkage involves a complex array of mechanosensitive proteins that change their affinities depending on force. The Peifer lab is interested in how this protein network allows for cell dynamics while maintaining epithelial integrity.

The protein Canoe (Cno), homologue of mammalian Afadin, plays a key role in the AJ-cytoskeletal linkage by interacting with junctional, cytoskeletal, and regulatory proteins. Cno has an upstream activator, the small GTPase Rap1, which is thought to binding to the two tandem RA domains on Cno.  Previous mutational analysis in our lab revealed that the RA domains are critical for all Cno functions.   The RA domains of Cno are dispensable for AJ localization but are critical for mechanosensitive Cno recruitment to AJs under elevated tension.  However, why Cno and Afadin both share TWO RA domains and what their individual functions are remained a mystery.  I am working with Dr. Kevin Slep, to take biochemical and structural biology approaches to this question. I aim to employ both binding assays and and atomic resolution protein crystallography to understand the molecular interactions taking place between the RA domains and Rap1, and investigate possible interactions with other small GTPases. In parallel, I am working with postdoc Dr. Corbin Jensen to generate and investigate RA domain and other Cno mutants that provide insight to the mechanisms that drive cell-cell adhesion under tension.

Publications

McParland, E.D,  Gurley, N.J., Wolfsberg, L.R., Butcher, T.A., Bhattarai, A., Jensen, C.C.,  Johnson, R.I.,  Slep, K.C.*, and  Peifer, M.* (2024) The dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis. *= co-corresponding authors. Journal of Cell Science, in press.  You can also view it on bioRxiv  [LINK]

 

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