Rajat Rohatgi

The paper uses base editing screens to identify second-site mutations that correct misfolded NPC1 proteins, enabling therapeutic applications for diseases like Niemann-Pick type C.

The paper systematically maps the sequence-function landscape of the WNT destruction complex using mutational scanning, identifying novel mutations and revealing substrate-assisted autoregulation mechanisms.

The paper describes the structure and function of a membrane-spanning E3 ubiquitin ligase complex, revealing its role in developmental processes and linking mutations to human birth defects.

This study shows that fatty acid metabolism regulates plasma membrane cholesterol accessibility through ATGL-dependent phospholipid remodeling, affecting membrane fluidity and cholesterol signaling.

The paper investigates cholesterol translocation mechanisms in the Smoothened receptor using simulations and experiments, showing that outer leaflet translocation has a lower energy barrier.

The paper identifies an ER pathway that regulates N-glycosylation by modulating OST-A activity, impacting cell-surface signaling and tissue development.

The paper shows that gene-teratogen interactions affect birth defect penetrance by altering Hedgehog signaling through the MMM complex and SMO degradation.

This study identifies a ubiquitin-based genetic mechanism linking Megf8 and Mgrn1 mutations to congenital heart defects and heterotaxy through altered Hedgehog signaling.

The paper identifies cis-regulatory elements by analyzing gene trap insertions in haploid human cells using WNT signaling screens.

The paper identifies a novel bile acid biosynthesis pathway in Smith-Lemli-Opitz syndrome that bypasses cholesterol, starting from 7-dehydrocholesterol, and links intermediates to Hedgehog signaling.

This study shows RSPO2 and RSPO3 can enhance WNT/β-catenin signaling without LGR receptors, while RSPO1 and RSPO4 cannot, revealing two distinct RSPO signaling mechanisms.

The paper shows cholesterol directly activates the GPCR Smoothened to drive Hedgehog signaling by binding its extracellular domain, independent of traditional GPCR mechanisms.