Linheng Li

Stowers Institute for Medical Research

Investigator, Stowers Institute for Medical Research.Adjunct Professor, University of Kansas Medical Center

Leadership council of NCI-designated Kansas University Cancer Center

Linheng is an international renown scientist in studying stem cells and their associated niches in hematopoietic and intestinal tissues. He was among the first to identify the endosteal niche in supporting hematopoietic stem cell (HSC), the first cellular component of niche identified in a mammalian system. He was also among the first to propose a model of co-existing reserve (a quiescent pool) and active adult stem cells in the same tissue in mammals. This concept not only provides an explanation for controversial observations of both quiescent and cycling stem cells in several tissues including bone marrow, intestine, and hair follicle in mammals, but also accounts for some aspects of drug resistance in cancer.

Linheng has contributed to the field by characterizing and demonstrating the roles of several developmental signaling pathways in regulation of stem cells. These include: FGF, IGF, and Notch, BMP, and Wnt signaling pertaining to self-renewal; the PTEN controlled PI3K-Akt signaling, in coordination with Wnt-b-catenin to promote HSC self-renewal; and the role of non-canonical Wnt signaling in maintaining quiescent stem cells. He shows a critical role of epigenetic (via DNA methylation and non-coding RNA) regulation of H19-Igf2 and Gtl2 maintains primitive stem cells via suppression of mitochondrial biogenesis and metabolism; as well as the Hoxb cluster that maintains normal stem cells but also contribute to leukemogenesis.

His recent works open possibilities of translational medicine including

1) Robust expanding human umbilical cord blood (UBC) HSCs by targeting Ythdf2,

2) Identification of mesenchymal stem cell (MSC) that facilitates cartilage regeneration,

3) Identification of cancer stem cell’s immune escaping mechanism mediated by b-catenin,

4) Tumor-initiating stem cell shape its microenvironment into an immunosuppressive barrier.

5) Development of drugs that target immune escape and immunosuppression. 

He has filed 6 patterns with 2 pending and 4 granted.