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Li Lab

We seek to understand the regulation of stem cells within blood stem cells and intestinal systems and how this relates to cancer in humans.

Research Summary

What mechanisms regulate stem cells that result in cancer?

Research Areas

Development and Regeneration, Genetics and Genomics, Molecular and Cell Biology

Organisms

Human cell lines, Mice

The Li Lab focuses on the hematopoietic (blood-forming) and intestinal systems to study stem cell development. Hematopoietic stem cells (HSCs) and intestinal stem cells (ISCs) are essential for health. In addition to renewing themselves, HSCs differentiate into red and white blood cells and platelets, and ISCs give rise to all types of intestinal epithelial cells for nutrient absorption, pathogen defense, and communication with the brain.

The Li Lab is working to understand how microenvironmental (niche) signals or intrinsic genetic and /epigenetic mechanisms regulate stem cell proliferation and differentiation in the hematopoietic and intestinal systems. The lab is also looking at how glitches or changes in these systems are associated with human diseases such as leukemia and colon cancer.

The lab discovered two sub-populations of blood forming cells, one active and one quiescent or waiting to become active – a kind of reserve population. The finding has implications for cancer treatment because tumors also contain active stem cells and a reservoir of backup cells, which may help explain why some tumors become resistant to treatment. The lab discovered that abnormal activation of Wnt and PI3K-Akt empowers leukemia stem cell drug-resistance and immune escape, in which beta-catenin, a downstream effector of Wnt signaling, can directly regulate multiple immune-checkpoint genes.

The Li Lab reported identification of therapy refractory tumor-initiating stem cells (TrTSC) in intestinal adenoma and uncovered that TrTSC shapes its microenvironment into an immunosuppressive barrier and a pro-tumorigenic niche.

Principal Investigator

Linheng Li

Investigator

Stowers Institute for Medical Research

Get to know the lab

Science

"Stem cell biology is the base for regenerative medicine as well as a key to understanding cancer. I think in my life, the next five or ten years, we will help translate what we discovered into clinical settings, including the ability to expand 'good' or healthy blood-forming stem cells and target 'bad' or cancer stem cells, both of which involve the niche concept."

Our Team


Visit the Lab

Featured Publications

Tumor-initiating stem cell shapes its microenvironment into an immunosuppressive barrier and pro-tumorigenic niche

He X, Smith SE, Chen S, Li H, Wu D, Meneses-Giles PI, Wang Y, Hembree M, Yi K, Zhao X, Guo F, Unruh JR, Maddera LE, Yu Z, Scott A, Perera A, Wang Y, Zhao C, Bae K, Box A, Haug JS, Tao F, Hu D, Hansen DM, Qian P, Saha S, Dixon D, Anant S, Zhang D, Lin EH, Sun W, Wiedemann LM, Li L. Cell Rep. 2021;36:109674.doi: 10.1016/j.celrep.2021.109674.

Overcoming Wnt-beta-catenin dependent anticancer therapy resistance in leukaemia stem cells

Perry JM, Tao F, Roy A, Lin T, He XC, Chen S, Lu X, Nemechek J, Ruan L, Yu X, Dukes D, Moran A, Pace J, Schroeder K, Zhao M, Venkatraman A, Qian P, Li Z, Hembree M, Paulson A, He Z, Xu D, Tran TH, Deshmukh P, Nguyen CT, Kasi RM, Ryan R, Broward M, Ding S, Guest E, August K, Gamis AS, Godwin A, Sittampalam GS, Weir SJ, Li L. Nat Cell Biol. 2020;22:689-700

N-Cadherin-Expressing Bone and Marrow Stromal Progenitor Cells Maintain Reserve Hematopoietic Stem Cells

Zhao M, Tao F, Venkatraman A, Li Z, Smith SE, Unruh J, Chen S, Ward C, Qian P, Perry JM, Marshall H, Wang J, He XC, Li L. Cell Rep. 2019;26:652-669 e656.

Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis

Qian P, De Kumar B, He XC, Nolte C, Gogol M, Ahn Y, Chen S, Li Z, Xu H, Perry JM, Hu D, Tao F, Zhao M, Han Y, Hall K, Peak A, Paulson A, Zhao C, Venkatraman A, Box A, Perera A, Haug JS, Parmely T, Li H, Krumlauf R, Li L. Cell Stem Cell. 2018;22:740-754 e747.

Suppression of m(6)A reader Ythdf2 promotes hematopoietic stem cell expansion

Li Z, Qian P, Shao W, Shi H, He XC, Gogol M, Yu Z, Wang Y, Qi M, Zhu Y, Perry JM, Zhang K, Tao F, Zhou K, Hu D, Han Y, Zhao C, Alexander R, Xu H, Chen S, Peak A, Hall K, Peterson M, Perera A, Haug JS, Parmely T, Li H, Shen B, Zeitlinger J, He C, Li L. Cell Res. 2018. Author Correction: Cell Res 2018:1-14. https://doi.org/10.1038/s41422-018-0072-0. Published online July 2018.;28:904-917.

The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism.

Qian P, He XC, Paulson A, Li Z, Tao F, Perry JM, Guo F, Zhao M, Zhi L, Venkatraman A, Haug JS, Parmely T, Li H, Dobrowsky RT, Ding WX, Kono T, Ferguson-Smith AC, Li L. Cell Stem Cell. 2016;18:214-228.

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