Current Research Interest
Cells encode their long-term “self” in chromatin marks that are, paradoxically, erased and rewritten reversibly. Our central question is therefore not “what marks exist?” but “how do reversible reactions maintain a stable equilibrium and what pushes the system over the ridge into disease?”
To dissect these processes, we combine wet-lab innovation with computational modelling, and we focus on two complementary systems: (1) Neuronal transcription and epigenetic homeostasis: How do neurons maintain activity-dependent gene programs for years? What breaks first in Alzheimer’s disease or addiction? (2) T-cell fate decisions: How does a T cell decide a balance between proliferating, killing, or exhaustion? Can we return the set-point to boost cancer therapy or curb autoimmunity?
We develop technologies to tackle these questions, including: single-cell temporal and spatial multi-omics, genome and epigenomic editing, and integrated computational analyses.
Scientific Contributions
1. Transcriptional condensates in expression control and stability (Cell 2024)
2. Attention network and cortical-thalamic circuity regulation (Nature 2020)
3. Single nucleus omics for neuron and neural stem cell (Science 2016)
4. Genome and epigenetic editing systems
5. Systems biology and gene circuit
Honors and awards
2019 MIT Technology Review, 35 under 35, China
2016 Extraordinary Potential Prize of 2016 Chinese Government Award for Students Abroad
2016 Wenner-Gren Fellowship
2013 McGovern Institute Fellowship
Selected Publications
1.He J*, Huo X*, Pei G*, Jia Z*, Yan Y, Yu J, Qu H, Xie Y, Yuan J, Zheng Y, Hu Y, Shi M, You K, Li T, Ma T, Zha ng MQ, Ding S, Li P#, Li Y#. Dual-role transcription factors stabilize intermediate expression levels. Cell. 2024 Apr 10:S0092-8674(24)00314-3.
2.Li Y, Lopez-Huerta VG, Adiconis X, Levandowski K, Choi S, Simmons SK, Arias-Garcia MA, Guo B, Yao AY, Blosser TR, Wimmer RD, Aida T, Atamian A, Naik T, Sun X, Bi D, Malhotra D, Hession CC, Shema R, Gomes M, Li T, Hwang E, Krol A, Kowalczyk M, Peça J, Pan G, Halassa MM, Levin JZ#, Fu Z#, Feng G#. Distinct subnetworks of the thalamic reticular nucleus. Nature. 2020, 583(7818):819-824.
3.Habib N*, Li Y*, Heidenreich M, Swiech L, Avraham-Davidi I, Trombetta JJ, Hession C, Zhang F#, Regev A#. Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons. SCIENCE. 2016, 353(6302):925-8.
