Daniel C. Link, M.D.

Alan and Edith Wolff Professor of Medicine
Internal Medicine
Oncology
Professor
Pathology and Immunology

Immunology Program
Molecular Cell Biology Program

  • 314-362-8771

  • 314-362-8872

  • 314-362-9333

  • 8007

  • 613 Southwest Tower

  • dlink@wustl.edu

  • genomics, hematopoiesis, microenvironment, MicroRNA, neutrophil, stem cells

  • Molecular regulation of normal and malignant hematopoiesis

Research Abstract:

Hematopoiesis, the process by which all blood cells are formed, is a tightly regulated process that is disrupted in a number of blood diseases, including leukemias. The main interest of our laboratory is to define the mechanisms that regulate normal and leukemic hematopoiesis. Current projects include the following:
1. Regulation of normal and malignant hematopoietic stem cells by the bone marrow microenvironment (stem cell niche). Studies are underway to characterize how normal (and leukemic) stem cells interact with stromal cells in the bone marrow to regulate their function. In particular, we are characterizing the mechanisms by which G-CSF alters the bone marrow microenvironment and leads to the mobilization of stem cells from the bone marrow to blood.
2. Molecular pathogenesis of therapy-related AML. Leukemia that arises following chemotherapy for a primary cancer is termed, therapy-related AML. We are using genomic approaches to identify genetic and epigenetic changes that contribute to this type of leukemia.
3. Characterization of the role of small non-coding RNAs in leukemia. Small non-coding RNAs include microRNAs, snoRNAs, piwiRNAs and others. There is emerging data suggesting that small non-coding RNAs may play an important role in the pathogenesis of human cancer. We are using genomic approaches and animal models to explore the role of certain dysregulated or mutated small non-coding RNAs in leukemia.

Selected Publications:

Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht T, Shen D, Hundai J, Fulton RS, Heath S, Baty JD, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley T, Link DC (corresponding author), and Wilson RK. The role of TP53 mutations in the origin and evolution of therapy-related AML. Nature, in press.

Schuettpelz LG, Borgerding J, Christopher M, Gopalan P, Romine MP, Herman AC, Woloszynek, Greenbaum AM and Link DC. G-CSF regulates hematopoietic stem cell activity, in part, through activation of toll-like receptor signaling. Leukemia, 28:1851, 2014.

Greenbaum A, Hsu MS, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, Nagasawa T, Link DC. CXCL12 production by early mesenchymal progenitors is required for hematopoietic stem cell maintenance. Nature, 495:227-30, 2013.

Greenbaum AM, Revollo LD, Woloszynek JR, Civitelli R, and Link DC. N-cadherin in osteolineage cell is not required for maintenance of hematopoietic stem cells. Blood, 120:295-302, 2012.

Schuettpelz L, Gopalan PK, Romine M, Fiuste F, and Link DC. Kruppel like factor 7 suppresses hematopoietic stem and progenitor cell function. Blood, 120:2981-9, 2012.

Welch, J.S., Ley, T.J., Link, D.C. (co-first author), Miller, C.A., Larson, D.E., Koboldt, D.C., Wartman, L.D., Lamprecht, T.L., Liu, F., Xia, J., et al. The origin and evolution of mutations in acute myeloid leukemia. Cell, 150:264-78, 2012

Link DC, Schuettpelz LG, Shen D, Wang J, Walter MJ, Kulkarni S, Ivanovich J, LeBeau M, Koboldt DC, Dooling DJ, Fulton RS, Schmidt H, Maupin R, O’Laughin M, Chen K, McLellan MD, Varghese N, Nagarajan R, Graubert T, Ding L, Ley TJ, Zambetti GP, Wilson RK, and Mardis ER. The identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA, 305:1568-76, 2011.

Christopher JM, Rao M, Liu F, Woloszynek JR, and Link DC. Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice. JEM, 208:251-60, 2011.

Last Updated: 9/19/2014 8:07:16 AM

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