Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded $174,744.00 to The Regents of the University of California, San Francisco under the Cardiovascular Diseases Research program (CFDA 93.837) to fund a five-year research project spanning June 2, 2026 through May 31, 2031. The project investigates the immunoregulatory role of the phosphatase SHP1 (Src Homology region 2 Domain-containing Phosphatase-1) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The research utilizes novel SHP1 allelic series mice containing patient-identified mutations to characterize the phospho-proteomic profiles associated with reduced phosphatase activity and hyperinflammation, employing mass spectrometry-based proteomics and preclinical models of ALI.

The primary deliverables include elucidation of SHP1's role in acute lung inflammation through comparative analysis of engineered mouse models and determination of whether pharmacologic activation of SHP1 can reduce inflammation in ALI settings. The research aims to identify SHP1-dependent intracellular signaling mechanisms that limit hyperinflammation and pulmonary hemorrhage, ultimately guiding the development of SHP1-activating therapeutic compounds and establishing the foundation for precision pharmacotherapies targeting hyperinflammation-associated lung injury. This project supports the investigator's transition to independent physician-scientist status within translational immunology and pulmonary disease research.