Daniel C. Link, M.D.

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

Cancer Biology Program
Immunology Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program

  • 314-362-8771

  • 314-362-8872

  • 314-362-9333

  • 613 Southwest Tower

  • dlink@wustl.edu

  • https://sites.wustl.edu/linklab/

  • Leukemia, clonal hematopoiesis, stem cells, niche, ribosome, cancer metabolism, neutrophils, genomics

  • Regulation of normal and malignant hematopoiesis

Research Abstract:

Our current research is focused on two general areas: characterizing the regulation of hematopoietic niches in the bone marrow under homeostatic and stress conditions and defining the molecular pathogenesis and treatment of leukemias. Cutting edge genomic, transgenic, and imaging approaches are being used in this research. The Link laboratory emphasizes a collaborative research environment and places a priority on the career development of its trainees. Highlights of current research include the following.
1. How do hematopoietic stem cells carrying mutations of TP53 transform to leukemia
2. How does transforming growth factor beta signaling in bone marrow stromal cells contribute to early B lineage specification and the development of myelofibrosis
3. What role do bone marrow resident dendritic cells play in the regulation of normal and malignant hematopoiesis
4. What are metabolic changes associated with T cell leukemia and can they be exploited to develop novel targeted therapies.
5. What role does ribosome (nucleolar) stress play in the pathogenesis of T cell leukemia.

Selected Publications:

1. Zhang J, Supakorndej T, Rao M, Krambs JR, Abou-Ezzi G, Ye RY, and Link DC. Bone marrow dendritic cells regulated hematopoietic stem/progenitor trafficking, JCI. in press.
2. Xia J, Miller CA, Baty J, Ramesh A, Jotte MRM, Fulton RS, Vogel TP, Cooper MA, Walkovich KJ, Makaryan V, Bolyard AA, Dinauer MC, Wilson DB, Vlachos A, Myers KC, Rothbaum RJ, Bertuch AA, Dale DC, Shimamura A, Boxer LA, Link DC. Somatic mutations and clonal hematopoiesis in congenital neutropenia. Blood. 2018;131(4):408-16. PMID: PMC5790127.
3. Wong TN, Miller CA, Jotte MRM, Bagegni N, Baty JD, Schmidt AP, Cashen AF, Duncavage EJ, Helton NM, Fiala M, Fulton RS, Heath SE, Janke M, Luber K, Westervelt P, Vij R, DiPersio JF, Welch JS, Graubert TA, Walter MJ, Ley TJ, Link DC. Cellular stressors contribute to the expansion of hematopoietic clones of varying leukemic potential. Nat Commun. 2018;9(1):455. PMID: PMC5792556.
4. Warner WA, Spencer DH, Trissal M, White BS, Helton N, Ley TJ, Link DC. Expression profiling of snoRNAs in normal hematopoiesis and AML. Blood Adv. 2018;2(2):151-63. PMID: PMC5787869.
5. Zhang J, Link DC. Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells. J Bone Miner Res. 2016;31(11):2001-7. PMID: PMC5523961.
6. Wong TN, Miller CA, Klco JM, Petti A, Demeter R, Helton NM, Li T, Fulton RS, Heath SE, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Welch JS, Graubert TA, Wilson RK, Ley TJ, Link DC. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood. 2016;127(7):893-7. PMID: PMC4760092.
7. Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, Heath S, Baty JD, Klco JM, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley T, Link DC (corresponding author), Wilson RK. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 2015;518(7540):552-5. PMID: PMC4403236.
8. Day RB, Bhattacharya D, Nagasawa T, Link DC. Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice. Blood. 2015;125(20):3114-7. PMID: PMC4432005.
9. Schuettpelz LG, Borgerding JN, Christopher MJ, Gopalan PK, Romine MP, Herman AC, Woloszynek JR, Greenbaum AM, Link DC. G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling. Leukemia. 2014;28(9):1851-60. PMID: PMC4130805.
10. Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, Nagasawa T, Link DC. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 2013;495(7440):227-30. PMID: PMC3600148.

Last Updated: 4/14/2021 8:22:43 AM

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