Rajat Rohatgi
Stanford University, CA·Biochemistry
Cells constantly send and receive chemical messages that tell tissues how to grow, take shape and repair themselves. When this cell-to-cell communication is damaged, the consequences span a lifetime, from birth defects to cancer and degenerative disease.
- Fields
Biochemistry
Genetics
Pharmacology
- Topics
signal transduction
Hedgehog signaling
WNT signaling
- Grants
- 3 known grants, through Mar 2031
What they work on
- Map the components and signaling steps of the pathway connecting N-glycosylation in the endoplasmic reticulum to WNT reception at the cell surface, using genome-wide CRISPR screens and mass spectrometry.
- Test how this glycosylation-sensing pathway shapes osteoblast differentiation and bone matrix production, using gene editing in cell lines and primary cells from patients with osteogenesis imperfecta.
- Define the biochemical function and developmental role of MOSMO, an uncharacterized four-pass membrane protein identified as a third component of the MEGF8-MGRN1 (MMM) ubiquitination pathway.
- Test whether the heterotaxy and heart defects of MMM-mutant mouse embryos arise from excess Hedgehog signaling at critical developmental stages, and search for other receptors the pathway controls.
- Assay rare coding variants in MMM genes found in patients with severe congenital heart defects using the lab's biochemical and mouse developmental assays for MMM protein function.
- Dissect the beta-catenin destruction complex, damaged in most colorectal cancers, with tiled base-editing mutational scanning, reconstitution from purified proteins, cell lines and organoids, seeking mutations that selectively disable the oncogenic complex.
- Discover and characterize membrane-tethered ubiquitin ligases, poorly understood assemblies that control the abundance of signaling receptors at the cell surface.
- Apply tools developed for measuring and perturbing accessible cholesterol to study how plasma membrane cholesterol accessibility governs signaling, trafficking and degenerative disease.
More about the research
The research program asks how cells set the volume on key developmental signals, especially by controlling how many receptors sit on the cell surface, and how these control systems fail in human disease. Three projects share that theme: one on the WNT signal and birth defects, one on the Hedgehog signal in left-right body patterning and heart formation, and a broader program on receptor regulation, cholesterol in membranes and the complex that destroys the WNT messenger protein in colorectal cancer.
Why it matters
Developmental defects are the leading cause of fetal loss and infant death, and genetic knowledge has not yet translated into prevention or treatment. By defining how cells tune WNT and Hedgehog signals, this work could lay groundwork for diagnostic and therapeutic strategies for birth defect syndromes, including severe congenital heart disease affecting roughly 7,000 U.S. babies a year, brittle-bone disease and congenital disorders of glycosylation. Work on the beta-catenin destruction complex and on membrane cholesterol may also point to new targets in colorectal cancer and chronic degenerative conditions.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jennifer Kong
University of Washington, WA·Biochemistry
Define the principles by which membrane-tethered E3 ubiquitin ligases, enzymes that tag proteins for destruction, recognize and target cell-surface receptors, mapping their target networks with mass spectrometry and biochemistry.
Tom A Rapoport
Harvard University, MA·Biochemistry
Determine how misfolded glycoproteins, proteins carrying sugar chains, are delivered to the Hrd1 complex and moved from the ER interior across the membrane, building on cryo-electron microscopy structures.
Amjad Javed
University of Alabama at Birmingham, AL·Biology
Measure natural Runx2 protein levels and stability in skeletal tissues of mice lacking Sp7, a bone-specific transcription factor, to test whether Sp7 is needed to keep Runx2 protein stable.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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