Department of Microbiology & Immunology

Columbia University Medical Center
Lei Ding, Ph.D.
Assistant Professor of Microbiology & Immunology and Rehabilitation & Regenerative Medicine
Ph.D., University of Colorado at Boulder

Mechanisms, particularly cell-extrinsic mechanisms, that regulate hematopoietic stem cell function

Research
Hematopoietic stem cells (HSCs) play critical roles in the generation, repair and homeostasis of the blood and immune system via self-renewal and multilineage differentiation. They are maintained for life through self-renewing divisions where HSCs divide to produces HSC daughter cells. How self-renewal is regulated is a central question in stem cell biology. HSC self-renewal is regulated by both HSC intrinsic and extrinsic mechanisms. In vivo, HSCs reside in a complex microenvironment and are critically regulated by factors secreted by cells that comprise a specialized niche. The HSC niche represents a critical element responsible for the extrinsic regulation of HSC self-renewal. Alterations to the microenvironment can contribute to the development of leukemia, bone marrow failure syndromes and anemia. We are investigating extrinsic mechanisms that regulate HSC self-renewal, and how mis-regulation of niche/HSC interactions contributes to diseases such as cancer and anemia. Understanding the HSC niche is a key step in helping design better strategies for in vitro expansion of HSCs, and for treatment of niche related diseases such as leukemia and anemia.


Selected Publications

  1. Zhou, B., Ding, L. and Morrison, S.J. (2015) Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1. Elife 4: e05521.
  2. Hayakawa, Y., Ariyama, H., Stancikova, J., Sakitani, K., Asfaha, S., Renz, B.W., Dubeykovskaya, Z.A., Shibata, W., Wang, H., Westphalen, C.B., Chen, X., Takemoto, Y., Kim, W., Khurana, S.S., Tailor, Y., Nagar, K., Tomita, H., Hara, A., Sepulveda, A.R., Setlik, W., Gershon, M.D., Saha, S., Ding, L., Shen, Z., Fox, J.G., Friedman, R.A., Konieczny, S.F., Worthley, D.L., Korinek, V. and Wang, T.C. (2015) Mist1 expressing gastric stem cells maintain the normal and neoplastic gastric epithelium and are supported by a perivascular stem cell niche. Cancer Cell 28: 800-814.
  3. Burberry, A., Zeng, M.Y., Ding, L., Wicks, I., Inohara, N., Morrison, S.J. and Nunez, G. (2014) Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling. Cell Host Microbe 15: 779-791.
  4. Chaix, J., Nish, S.A., Lin, W.H., Rothman, N.J., Ding, L., Wherry, E.J. and Reiner, S.L. (2014) Cutting edge: CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal. J. Immunol. 193: 1013-1016.
  5. Oguro, H., Ding, L. and Morrison, S.J. (2013) SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell 13: 102-116.
  6. Ding, L. and Morrison, S. (2013) Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature dpi:10.1038. Published online Feb 24, 2013.
  7. Ding, L., Saunders, T., Enikolopov, G. and Morrison, S. (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481: 457-462
  8. Ding, L. and Han, M. (2007) GW182 family proteins are critical for miRNA-mediated gene silencing. Trends in Cell Biology 17: 411-416.
  9. Zhang, L.*, Ding, L.*, Cheung, T., Dong, M., Chen, J., Sewell, A., Liu, X., Yates, J. and Han, M. (2007) Systematic identification of miRISC proteins, miRNAs, and their mRNA targets in C. elegans by their interactions with GW182 family proteins AIN-1 and AIN-2. Molecular Cell 28: 598-613 (*equal contribution)
  10. Ding, L., Spencer, A., Morita, K. and Han, M. (2005). The developmental timing regulator AIN-1 interacts with argonaute protein ALG-1, miRISCs and may target ALG-1 to cytoplasmic P bodies in C. elegans. Molecular Cell 19: 437-447.

Assistant Professor Lei Ding
Phone: 212-305-7468
Lab Phone: 212-305-7468
Fax: 212-305-1468
Email:  ld2567@columbia.edu


Department of Microbiology & Immunology, Columbia University + 701 W. 168 St., HHSC 1208 New York, NY 10032 Tel. 212-305-3647