Linheng Li, PhD

Investigator, Stowers Institute for Medical Research
Professor of Pathology and Laboratory Medicine

Ph.D.: New York University Medical Center
Postdoctoral: The Dr. Leroy Hood Lab, University of Washington


Li Lab web site (Stowers)

Ph.D. students are welcome. Contact me for more info.

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. We mainly focus 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, we use the combined approaches described as follows:

  • To identify the location (or niche) where hematopoietic and intestinal stem cells reside, and to further investigate the interaction between stem cell and its niche and dissect the key signals emanating from the niche, such as the Wnt, BMP, and PTEN signals.
  • To characterize the functions of the niche signals in stem cell regulation, we use 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 system. This information should reveal how they may malfunction or be altered in association with human diseases, such as leukemia and colon cancer.

Selected Publications

Haug, J.S., He, X.C., Grindley, J.C., Wunderlich, J.P., Gaudenz, K., Ross, J.T., Paulson, A., Wagner, K.P., Xie, Y., Zhu, R., Yin, T., Perry, J. M., Hembree, M. J., Redenbaugh, E. P., Radice, G. L., Seidel, C., and Li, L. (2008). N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells. Cell Stem Cell 2, 367-379. AbstractEditorial Note

He, X.C., Yin, T., Grindley, J.C., Tian, Q., Sato, T., Tao, W.A., Dirisina, R., Porter-Westpfahl, K.S., Hembree, M., Johnson, T., Wiedemann, L. M. Barrett, T. A. Hood, L. Wu, H. Li, L.. (2007). PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 39, 189-198. Abstract

Zhang, J., He, X.C., Tong, W.G., Johnson, T., Wiedemann, L.M., Mishina, Y., Feng, J.Q., and Li, L. (2006). Bone morphogenetic protein signaling inhibits hair follicle anagen induction by restricting epithelial stem/progenitor cell activation and expansion. Stem cells (Dayton, Ohio) 24, 2826-2839. Abstract

J. Zhang, J. C. Grindley, T. Yin, S. Jayasinghe, X. C. He, J. T. Ross, J. S. Haug, D. Rupp, K. S. Porter-Westpfahl, L. M. Wiedemann, H. Wu, & L. Li "PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 2006 441:518-522.CoverNews & Views.,  Abstract, and corrected Sup-Fig.4

Tian Q, Feetham MC, Tao WA, He XC, Li L, Aebersold R, Hood L. Proteomic analysis identifies that 14-3-3{zeta} interacts with {beta}-catenin and facilitates its activation by Akt. Proc Natl Acad Sci U S A.2004. Abstract

He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.Nat Genet.2004;36:1117-1121. Abstract. The comments regarding this paper News and Views.

Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harri S, Wiedemann LM, Mishina Y, Li L.. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836-841. Abstract, comments regarding this paper News and Views, and a featured article by Nature.

Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J and Li L.  Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood. 2003;101.2:383-389. Abstract, The comments regarding this paper Comments.

Park I, He Y, Lin F, Laerum O, Tian Q, Bumgarner R, Klug C, Li K, Kuhr C, Doyle M, Xie X, Schummer M, Sun Y, Goldsmith A, Clarke M, Weissman I, Hood L, Li L.  Differential Gene Expression Profiling of Adult Murine Hematopoietic Stem Cells. Blood. 2002;99:488-498. Abstract

Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL.  From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci USA. 2001;98:7934-7939.Abstract

Li L, Milner L, Deng Y, Iwata W, Banta A, Graf L, Marcovina S, Friedman C, Trask B, Hood L, Torok-Storb B.  The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity. 1998;8:43-55. Abstract

Li L, Krantz ID, Deng Y, Genin A, Banta A, Collins C, Qi M, Trask BJ, Kuo W, Cochran J, Costa T, Pierpont MEM, Rand EB, Piccoli D, Hood L, Spinner N.  Alagille syndrome is caused by mutations in hJagged1 (JAG1), which encodes a ligand for Notch1. Nature Genetics. 1997;16:243-251. Abstract. Comments regarding this paperNews and Views.

Invited Reviews and Previews

Perry, J.M., and Li, L. (2008). Self-renewal versus transformation: Fbxw7 deletion leads to stem cell activation and leukemogenesis. Genes & development 22, 1107-1109. Abstract

Scoville, D. H., Sato, T., He, X. C., and Li, L. (2008) Gastroenterology 134(3), 849-864. Abstract

Perry, J.M., and Li, L. (2007). Disrupting the stem cell niche: good seeds in bad soil. Cell 129, 1045-1047.Abstract

T. Yin and L. Li. The stem cell niche in bone. J Clin Invest. 2006 116(5):1195-201 Abstract

Li, L. Neaves WB. Stem Cells and Cancer Stem Cells: the Niche Matters. Cancer Res.2006;66:4553-4557.Abstract

Jason T. Ross, and Li. L. (2006). Recent advances in understanding extrinsic control of hematopoietic stem cell fate. Current opinion in hematology 13, 237-242. Abstract

Li, Z., and Li, L. (2006). Understanding hematopoietic stem-cell microenvironments. Trends in biochemical sciences 31, 589-595. Abstract

Li L. Find the Hematopoietic Stem Cell Niche in Placenta. Dev Cell.2005;8:297-304. Abstract

Li L, Xie T. Stem Cell Niche: Structure and Function. Annu Rev Cell Dev Biol.2005;17:605-631. Abstract

He XC, Zhang J, Li L. Cellular and molecular regulation of hematopoietic and intestinal stem cell behavior.Book Chapter for Ann Rev N.Y. ACAD; In: Stem Cell Biology: Development and Plasticity; 2005;1049:28-38.Abstract

Zhang J, Li L. BMP signaling and stem cell regulation. Dev Biol.2005. Abstract

Book chapters

Scoville, D. He, X., Lee, G., Sato, T., Barrett, TA., Li, L. Intestinal Stem Cells in Physiologic Regeneration and Disease. In: Moody, SA (ed.) Principles of Developmental Genetics. Washington, DC: Elsevier Academic Press. (2007) July 2007.

 

Last modified: Aug 26, 2014

Contact

Linheng Li, PhD
Investigator, Stowers Institute for Medical Research
Professor of Pathology and Laboratory Medicine

lil@stowers.org

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