hPSCs as a model to probe the logic of human cell fate

We apply precision gene editing and large-scale CRISPR screening in human pluripotent stem cells (hPSCs) to explore mechanisms underlying human development. Specifically, we are interrogating the protein-coding regulators of pancreatic development and β cell function. The pathways that regulate these processes can be exploited for therapeutics to prevent and reverse diseases such as type 1 and type 2 diabetes. In a second, closely related area, we are developing approaches to discover developmental enhancers, and to understand the epigenetic regulation of noncoding regulatory elements with a focus on DNA methylation.

Huangfu Lab 2026

What we work on

Our lab combines genome-scale CRISPR screening, functional and computational genomics in hPSCs to dissect the regulatory logic of cell fate decisions in development and disease.

Pancreatic Development & β Cell Biology

We study the transcriptional and epigenetic programs that drive pancreatic lineage commitment and β cell maturation, using hPSC differentiation as a tractable human model.

Genome-Scale CRISPR Screening

We develop and apply large-scale CRISPRi and knockout screens to systematically identify genes and regulatory elements controlling cell identity across developmental transitions.

Epigenetic Regulation & DNA Methylation

We investigate how noncoding regulatory elements — particularly DNA methylation valleys and developmental enhancers — are established and maintained to control gene expression.

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Selected work

Recent publications from the lab.

Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation

Xian Zhang, Wilfred Wong, Hyein S. Cho, Dapeng Yang, Gary Dixon, Renhe Luo, Dingyu Liu, Denis Torre, Shigeaki Umeda, Federico González, Gokce Askan, Aslihan Yavas, Jeyaram Ravichandran Damodaran, Robert W. Rickert, Rajya Kappagantula, Fong Cheng Pan, Victoria G. Aveson, Adrien Grimont, William B. Fall, Xianming Wang, Julian Pulecio, Samuel J. Kaplan, Heng Pan, Xianlu Laura Peng, Jen Jen Yeh, Steven D. Leach, Christine A. Iacobuzio-Donahue, Rohit Chandwani, Christina S. Leslie, Danwei Huangfu

Developmental Cell

2026

Functional chromatin signatures premark future lineage-specific enhancers

Julian Pulecio, Zakieh Tayyebi, Dingyu Liu, Wilfred Wong, Renhe Luo, Jeyaram R. Damodaran, Samuel J. Kaplan, Nan Hu, Hyein S. Cho, Jielin Yan, Dylan Murphy, Robert W. Rickert, Abhijit Shukla, Aaron Zhong, Denis Torre, Qianzi Li, Federico González, Dexin Yang, Wenbo Li, Ting Zhou, Effie Apostolou, Christina S. Leslie, Danwei Huangfu

Cell Genomics

2026

Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells

Jielin Yan, Renhe Luo, Bess P. Rosen, Dingyu Liu, Wilfred Wong, Christina S. Leslie, Danwei Huangfu

Stem Cell Reports

2025

Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness

Bess P. Rosen, Qing V. Li, Hyein S. Cho, Dingyu Liu, Dapeng Yang, Sarah Graff, Jielin Yan, Renhe Luo, Nipun Verma, Jeyaram R. Damodaran, Hanuman T. Kale, Samuel J. Kaplan, Michael A. Beer, Simone Sidoli, Danwei Huangfu

Nature Communications

2024

CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant

Samuel Joseph Kaplan, Wilfred Wong, Jielin Yan, Julian Pulecio, Hyein S. Cho, Qianzi Li, Jiahui Zhao, Jayanti Leslie-Iyer, Jonathan Kazakov, Dylan Murphy, Renhe Luo, Kushal K. Dey, Effie Apostolou, Christina S. Leslie, Danwei Huangfu

Cell Reports

2024
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News & updates

Recent awards, fellowships, and milestones from the lab.

2025

Denis Torre awarded the Damon Runyon Cancer Research Foundation Fellowship. Fellowship

2025

Tamara Casteels receives the Emerald Foundation Postdoctoral Fellowship. Fellowship

2025

Pallavi Mohapatra receives the Kaufman Family Postdoctoral Fellowship in Pediatric Cancer. Fellowship

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