Kelsey J. Roberts

TL;DR: The crystal structure of active mouse SMO in complex with the SAG21k agonist and a stabilizing intracellular binding nanobody reveals the structural basis of SMO regulation by PTCH1, and suggests a strategy for overcoming clinical resistance to SMO inhibitors.

TL;DR: Understanding and therapeutic harnessing of the role of stroma in cancer restraint may hinge on knowledge of the signaling programs elaborated by the stromal niche.

TL;DR: An agonist is developed, a conformation-specific nanobody that potentially targets the conformational changes of the Hedgehog receptor Patched1 and potently activates the pathway in vivo, facilitating mechanistic studies of Hedgehog pathway activation and the engineering of pathway activating agents for therapeutic use.

TL;DR: Patched expression indeed reduces cholesterol activity in the inner leaflet of the plasma membrane, in a manner antagonized by Hedgehog stimulation and with implications for regulation of Smoothened.