Rami Hannoush

Rami Hannoush

Principal Scientist and Group Leader
Genentech
South San Francisco, CA
USA
 650-467-3696
 hannoush.rami@gene.com

Abstract

Challenges and Emerging Approaches in Peptide Drug Discovery: Applications in Modulating Stem Cells

This talk will describe our group's efforts in discovering and optimizing peptide-based scaffolds, and will highlight some of the challenges and novel technologies for peptide lead identification and development. A case study on selectively targeting the Frizzled, FZD, receptor class will be discussed.

In particular, FZD7 receptor is enriched in LGR5+ intestinal stem cells and plays a critical role in their self-renewal. FZDs interact with Wnt signaling proteins via, in part, a lipid-binding groove on the extracellular cysteine-rich domain, CRD, of the FZD receptor.

The presentation will highlight our lab’s recent efforts in providing new biochemical and structural insights into the molecular arrangement of members of the FZD receptor family and their mode of regulation by cis-unsaturated fatty acids. We also describe the identification of a potent peptide that selectively binds to the FZD7 CRD at a previously uncharacterized site and alters the conformation of the CRD and the architecture of its lipid-binding groove, revealing a new approach for targeting specific FZD isoforms. Treatment with the FZD7-binding peptide impaired Wnt signaling in cultured cells and stem cell function in intestinal organoids.

Authors

Rami Hannoush

Affiliations

Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA

Lecture Images

Rami Hannoush presenting at APS2019 Rami Hannoush presenting at APS2019 Rami Hannoush presenting at APS2019