Han-Yu Shih, PhD

Stadtman Investigator
Neuro-Immune Regulome Unit

shihPrecise orchestration of gene regulation in lymphocytes is mediated by networks of signaling molecules, transcription factors, and genomic regulatory regions, which in sum is termed regulomes. Previously, we have identified lineage-specific regulomes in tissue-resident innate and adaptive lymphocytes in both homeostatic and activated states by integrating cutting-edge techniques and computational approaches (Shih et al., Cell, 2016; Sciume et al., 2020). We are currently focusing on two key biological questions: 1) How do distinct stimuli regulate cytokines in a context-specific manner? 2) How do cytokines contribute to the progression of neurodegeneration, such as Alzheimer’s disease and Glaucoma? By analyzing lymphocyte regulomes in engineered mice, we aim to further our understanding of molecular mechanisms that contribute to neuroinflammatory and neurodegenerative diseases.

Current Projects:

  1. Determining the roles of 3D chromatin architecture in differential cytokine regulation in innate and adaptive lymphocytes      
  2. Understanding how lymphocytes contribute to the progression of age-related neurodegeneration in Alzheimer’s disease
  3. Dissecting the role of lymphocytes in injury-induced neuropathy
  4. Identifying regulatory networks for cytokine production in Th1 and pathogenic Th17 cells

References:

  • Fernando N, Sciumè G, O’Shea JJ, Shih HY. Multi-dimensional gene regulation in innate and adaptive lymphocytes: A view from regulomes. Frontiers in Immunology. 2021
  • Sciumè G, Mikami Y, Jankovic D, Nagashima H, Villarino AV, Morrison T, Yao C, Signorella S, Sun HW, Brooks SR, Fang D, Sartorelli V, Nakayamada S, Hirahara K, Zitti B, Davis FP, Kanno Y, O’Shea JJ, Shih HY. Rapid enhancer landscape remodeling and transcription factor repurposing enable high magnitude gene induction upon acute activation of NK cells. Immunity. 2020

Suggested Penn mentors: Kelly Jordan Sciuto, Jorge Alvarez, Chris Hunter