Zhongqi “Jason” Lin

Stem cell differentiation follows a stereotyped gene-expression pattern, yet each gene is transcribed in stochastic bursts. Using intravital two-photon imaging of live mouse epidermis, I track transcription and protein dynamics to ask how bursting kinetics, neighbor communication, and where transcripts and proteins localize, within individual cells and across the tissue, are coordinated with cell behaviors to orchestrate differentiation within an intact tissue architecture.

In a living animal, transcription sites are small foci with low signal-to-noise that switch on and off inside nuclei that move and rise as cells delaminate. To follow these cells and their activity over time, I developed a pipeline that segments thousands of nuclei in 3D with a model trained on our custom dataset, places each along the differentiation continuum by its delaminated distance above the basement membrane, and tracks the transcriptional bursting over time. This system enables high-throughput interrogation of dynamic transcriptional activity during continuous stem cell turnover, over hours, days, and weeks.

Intravital imaging generates large 4D datasets across animals, conditions, and time points, and a single broken metadata link can render a result untraceable and irreproducible. I design data infrastructure (schemas, standardized file structures, raw-to-derived linkages, and per-experiment HTML QC reports) so that each new dataset becomes a queryable object with full provenance from raw image to final figure.

Rathkey JK, Choi SS, van Unen V, … Lin Z, … Kuo CJ

Grown from intact pieces of adult human lung at an air-liquid interface, these organoids keep the lung’s own resident immune cells. SARS-CoV-2 infects the organoid epithelium and sets off virus-specific, tissue-resident T cell responses, and priming those T cells with viral peptides curbs later infection: the lung can mount antiviral T cell memory without a lymph node.

Swaminathan A, Gonzalez DG, Matte-Martone C, Xu F, Simpson D, Moore JL, Lin Z, Rana U, Monedero-Alonso D, Mack JJ, Kam CY, Greco V

In live mouse skin, just over half of capillary endothelial cells show Ca²⁺ activity at any moment, and the same cells stay active for days to weeks. Without the gap junction protein Cx43, a subset of cells becomes persistently active, making vessels leaky and disrupting blood flow.

Santos AJM, van Unen V, Lin Z, Chirieleison SM, Ha N, Batish A, … Sollid LM, Fernandez-Becker NQ, Davis MM, Kuo CJ · 31 authors

Preserving the gut epithelium with its resident immune cells, this human organoid model of coeliac disease recreates gluten-dependent damage, shows that gluten-induced IL-7 is necessary and sufficient for epithelial destruction, and establishes a proof of principle for organoid models of autoimmunity.

Chen JK, Wiedemann J, Nguyen L, Lin Z, Tahir M, Hui CC, Plikus MV, Andersen B

IRX5 is required for DNA damage repair and cell-cycle progression in hair follicle stem cells at the telogen-to-anagen transition, and in their progeny in early anagen follicles.

Lin Z, Jin S, Chen J, Li Z, Lin Z, Tang L, Nie Q, Andersen B

Epidermal differentiation is continuous and gradual, with a single commitment point at which cells switch from a plastic state to irreversible differentiation. GRHL3 gates both ends: it restrains Wnt-driven stem cell expansion early and drives terminal differentiation late.