Wenqi Wang
University of California-Irvine, CA·Biochemistry
How do cells and tissues know when to grow and when to stop? A central answer is the Hippo pathway, a chain of signaling proteins that controls cell division, regeneration, tissue balance and organ size.
- Fields
Biochemistry
Biology
Pharmacology
- Topics
Hippo pathway
Hippo signaling
kinase signaling
- Grants
- 3 known grants, through Jul 2031
What they work on
- Characterize the molecular architecture of the Hippo kinase cascade, the chain of phosphate-adding enzymes MST and LATS and their partners, and map the regulatory networks around it.
- Determine how growth signals such as growth factors, energy status, cell-cell contact and mechanical cues converge on components of the Hippo pathway.
- Define how energy stress activates the Hippo pathway through the AMPK-STRIPAK-MAP4K axis, linking the cell's energy sensor to kinases that switch on LATS.
- Investigate a function of the Hippo pathway that is independent of the growth protein YAP and helps cells survive energy stress.
- Characterize the Hippo pathway-mediated response to heavy metals in vivo and determine how the pathway regulates MTF1, the transcription factor that activates metal-defense genes.
- Determine how heavy metals such as cadmium, zinc and copper in turn regulate the Hippo pathway, testing a two-way link between metal balance and growth signaling.
More about the research
The pathway gathers growth-related signals, such as growth factors, energy levels, contact with neighboring cells and mechanical forces, and uses them to turn growth genes on or off. When it goes wrong, it is linked to human diseases including cancer. In mammals, its core is a cascade of two kinases (enzymes that add phosphate tags to proteins), MST and LATS, with helper proteins SAV1 and MOB1. Active LATS tags the protein YAP, which keeps it out of the nucleus. Untagged YAP enters the nucleus and partners with the transcription factor TEAD to switch on growth genes. Three projects ask how this pathway is built, how outside signals reach it, and what new jobs it performs, including an unexpected role in handling toxic metals.
Why it matters
Because the Hippo pathway is often disrupted in human diseases such as cancer, learning how it is assembled and switched on by energy stress could point to new treatment strategies. The heavy-metal project may inform therapies for metal poisoning and for diseases caused by faulty metal balance, which affect organs such as the liver, kidney and nervous system, with children at particular risk.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kenneth Irvine
Rutgers University-New Brunswick, NJ·Biology
Determine how phase-separated condensates of Warts with Jub, and Jub-promoted phosphorylation of the Warts N-terminus, inhibit this Hippo pathway kinase in Drosophila tissues.
Jing Yang
University of California-San Diego, CA·Biochemistry
Determine how the Hippo pathway, through the LATS1/2 kinases, controls transcription of ESR1, the main estrogen receptor gene, in breast cells and what ESR1 contributes to Hippo biology in breast tissue.
Jyoti Misra
Stony Brook University, NY·Genetics
Test how the endocytic machinery that internalizes surface proteins, together with a competitive inhibitor, establishes and maintains the spatial organization of Dachsous–Fat signaling across Drosophila tissues.
The school
University of California-Irvine: 46 labs on PI Pages, $645M a year on research, 524 research doctorates a year.
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