Regulatory protein
YAP
A protein involved in tissue repair and the activation of apoptosis through interaction with p73
Hypotheses on this target 5
Inhibition3
Activation2
Lower level
Higher level
Protection from degradation
Function restoration
Function preservation
Inhibition3
Late Yes-associated protein activity may limit skin scarring by killing damaged repair cells
Where this hypothesis actsPhotodamaged skin undergoing dermal repair after repeated injury
What is proposedSuppress activity temporarily, then restore a short late pulse
With whatNot stated in the record
HowControl YAP activity over time while preserving its Tyr357 phosphorylation and interaction with p73 during the late pulse
Possible resultPossible reduction in residual contracture and scarring while preserving tensile strength
2026-09-26
The link between resolving inflammation and fibrosis is an artefact of culture plastic
Where this hypothesis actsHuman macrophages cultured on substrates with different stiffnesses
What is proposedPrevent nuclear localization and the associated co-activation of TGFB1 transcription
With whatPhysical or surgical intervention
HowCulture macrophages on physiologically compliant substrates, using 2 kPa polyacrylamide gels in the proposed test
Possible resultExpected absence of M2-associated TGF-β1 upregulation on compliant substrates
2026-09-14
Less variable Yes-associated protein gene activation timing may widen safe suppression windows
Where this hypothesis actsSkin after repeated injury, when repair and profibrotic programs overlap across cells
What is proposedSuppress YAP with an experimentally varied start time
With whatNot stated in the record
HowIndependently vary the onset of YAP suppression and transcriptional response variability; the suppression technique is not stated
Possible resultPossible prevention of scarring while preserving tissue strength and barrier repair
2026-09-25
Activation2
Surviving skin fibroblasts must briefly dismantle their contractile machinery to stop pulling
Where this hypothesis actsSurviving fibroblasts in aged skin after wound closure, under matrix tension
What is proposedBriefly activate YAP to permit contractile disassembly while maintaining survival
With whatNot stated in the record
HowAppropriately timed activation followed by withdrawal; the activation method is not stated in the record
Possible resultPossible termination of contraction and recovery of mobility without cell loss, senescence, or continued proliferation
2026-09-21
Regulatory partners determine whether a signal sustains or ends fibroblast contraction
Where this hypothesis actsFibroblasts after closure, with controlled tension and partner-specific enhancer occupancy
What is proposedIncrease YAP activity when the repair/disassembly program is selected
With whatControlled genetic model
HowInducible fibroblast-specific YAP perturbation combined with independently controlled loading and targeted enhancer perturbation
Possible resultPossible termination of contraction when YAP amplifies the repair/disassembly program
2026-09-21