Kent Lin

Program: Molecular Cell Biology

Current advisor: Marco Colonna, MD

Undergraduate university: Missouri University of Science and Technology, 2015

Enrollment year: 2018

Research summary
Studying microglia receptor modulating pathways in the context of CNS diseases.

Genome-wide association studies (GWAS) and whole exon sequencing studies have demonstrated that several AD-risk polymorphisms affect molecules expressed in microglia, suggesting that microglial responses to AD pathology play a crucial role in the onset and/or progression of AD. In this regard, polymorphic variants of Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRα) are associated with AD risk. PILRα is a cell surface receptor expressed on myeloid cells such as monocytes, neutrophils, and microglia in the central nervous system (CNS). PILRα contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) that transmits intracellular inhibitory signals by recruiting the protein tyrosine phosphates SHP-1. The impact of PILRα-dependent signals in microglia and on AD pathology has not been studied. Based on these premises, we speculate that PILRα is expressed in microglia during AD and that PILRα polymorphisms associated with AD promote the onset and/or progression of AD by impairing microglia response to brain pathology.

Graduate publications
Wang S, Sudan R, Peng V, Zhou Y, Du S, Yuede CM, Lei T, Hou J, Cai Z, Cella M, Nguyen K, Poliani PL, Beatty WL, Chen Y, Cao S, Lin K, Rodrigues C, Ellebedy AH, Gilfillan S, Brown GD, Holtzman DM, Brioschi S, Colonna M. 2022 TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell, 185(22):4153-4169.e19. PMCID: PMC9625082

Gallardo G, Wong CH, Ricardez SM, Mann CN, Lin KH, Leyns CEG, Jiang H, Holtzman DM. 2019 Targeting tauopathy with engineered tau-degrading intrabodies. Mol Neurodegener, 14(1):38. PMCID: PMC6805661