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Unraveling the Molecular Mechanisms of the MRAS-SHOC2-PP1C Complex

Award Number: R15GM163260
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Unraveling the Molecular Mechanisms of the MRAS-SHOC2-PP1C Complex - Abstract The SMP complex, composed of SHOC2, MRAS, and PP1C, plays a crucial role in regulating the RAS-MAPK signaling pathway by facilitating RAF dephosphorylation and activation. Despite its significance in oncogenic and developmental signaling, the molecular mechanisms governing SMP complex assembly and function remain poorly understood. This proposal aims to elucidate the structural and biochemical basis of SMP complex formation, develop novel chemical probes to selectively disrupt its function, and investigate the roles of MRAS and SHOC2 in SMP complex assembly. Using an integrative approach that combines structural biology, chemical biology, medicinal chemistry, computational simulations, biophysical approaches, and cellular assays, we will define the key molecular interactions driving SMP complex activity. Furthermore, our chemical probes will serve as powerful tools to dissect the functional consequences of SMP disruption and lay the foundation for therapeutic strategies targeting aberrant RAS signaling. Collectively, this work will advance our understanding of SMP-mediated signal regulation and uncover potential avenues for therapeutic intervention in RAS-/RAF-driven malignancies and RASopathies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $581,250 )
2026	2026	ROWAN UNIVERSITY	201 MULLICA HILL RD	GLASSBORO	NJ	08028	GLOUCESTER	USA	Biomedical Research and Research Training	000	1	4/28/2026	NEW	$581,250
														Subtotal = $581,250

Grand Total All Awards = $581,250

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Unraveling the Molecular Mechanisms of the MRAS-SHOC2-PP1C Complex

Award Number: R15GM163260

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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