Linheng Li, PhD

Investigator, Stowers Institute for Medical Research
Co-leader, Cancer Biology, The University of Kansas Cancer Center
Professor of Pathology and Laboratory Medicine, The University of Kansas School of Medicine

Stem cells are the key subset of cells in the body functioning as ancestor cells to produce various functionally specialized mature cells (differentiation) in a given tissue, while simultaneously maintaining the capacity to continuously divide and reproduce themselves (self-renewal). This self-renewal process is controlled by intrinsic genetic pathways that are subject to regulation by extrinsic signals from the microenvironment in which stem cells reside. Stem cells play essential roles ranging from embryonic development and organogenesis (fetal stem cells including embryonic stem cells) to tissue homeostasis and regeneration (adult stem cells). Stem cell development is a complex process, and a precise balance is maintained among different cell events including self-renewal, differentiation, apoptosis (cell death), and migration. Loss of this balance tends to lead to uncontrolled cell growth or cell death, thereby developing into a variety of diseases including cancer or tissue defects.

Dr. Li focuses on two systems to study stem cell development: hematopoietic and intestinal stem cell compartments. The hematopoietic system facilitates functional characterization of stem cells as bone marrow transplantation experiments can be readily performed. The intestinal system has a well-organized developmental architecture in which stem cell marking and lineage tracing can be used to investigate how stem cells are maintained by their microenvironment (niche), how stem cells undergo asymmetric division to keep the balance between self-renewal and lineage commitment, and what molecular signals are involved in this regulation. To investigate the molecular mechanisms that control stem cell properties, he uses the combined approaches described as follows:

  • To take a global view of changes in the gene expression patterns during hematopoietic stem cell development to reveal important pathways regulating self-renewal and lineage commitment. The Notch, Wnt, BMP, and PTEN signal pathways have been well documented to be involved in developmental regulation and tumorigenesis. We mainly focus on studying Wnt, BMP, and PTEN for their roles in the regulation of hematopoietic and intestinal stem cell proliferation and differentiation.
  • To understand the epigenetic regulation including histone modification and DAN methylation modification such as at the imprinting gene loci during the state change and fate determination of hematopoietic and intestinal stem cells.
  • To further characterize the functions of these pathways with genetic approaches such as transgenic or gene targeting animal models to examine their influence on stem cell development. Our goal is to understand how these signal pathways or mechanisms regulate normal development in the hematopoietic and intestinal systems. This information should reveal how they may malfunction or be altered in association with human diseases such as leukemia and colon cancer.

Dr. Li received a Master of Science degree in Genetics from Fudan University in Shanghai, P.R. China, and Master of Science and Doctorate degrees in Molecular and Cellular Biology from New York University Medical School.

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