• 1588 Citations
19992020

Research output per year

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Personal profile

Research interests

The Schuettpelz Lab is interested in understanding how inflammatory signals regulate hematopoietic stem cells (HSCs). In particular, we are studying the role of toll-like receptor (TLR) signaling in HSCs. TLRs are a family of pattern-recognition receptors that respond to pathogens and play a central role in the innate immune response. While much of the research on TLRs has focused on more committed effector cell types, recent studies suggest that TLRs may even influence the immune response from the level of the HSC. Both mouse and human HSCs express TLRs (Nagai, et al Immunity 2006; Sioud, et al J Mol Biol 2006), and in vitro exposure to TLR agonists has been shown to stimulate HSC cycling and skew HSC differentiation toward the myeloid lineage. Furthermore, chronic in vivo treatment of mice with the TLR4 agonist LPS leads to increased HSC cycling and expansion, but decreased repopulating activity with myeloid skewing in transplantation assays (Esplin, et al J Immunol 2011). Together, these studies suggest that TLR signaling may shape the immune response from the level of the HSC, regulating the proliferation, differentiation and activity of these cells. Finally, enhanced expression of TLRs and increased TLR signaling is associated with myelodysplastic syndrome (MDS), a stem cell disorder characterized by ineffective hematopoiesis and a high risk of transformation to acute leukemia (Maratheftis, et al Clin Cancer Res 2007; Hoffman, et al Blood 2002; Starczynowki, et al Nature Medicine 2010; Wei, et al Leukemia 2013). Our lab is currently using mouse models to better define the role of individual TLRs in regulating HSC function. In addition, we are exploring the connection between enhanced TLR signaling and MDS through the use of various mouse models of this disease. Ultimately we hope that a better understanding of how inflammation and TLRs regulate HSCs will lead to the clinical application of specific agonists or antagonists to improve HSC function in patients undergoing bone marrow transplantation or suffering from bone marrow failure or hematopoietic malignancies.

Areas of Clinical Interest

Pediatric cancer, blood disorders in children, genetic components of cancer in children

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Research Output

Contribution of Aberrant Toll Like Receptor Signaling to the Pathogenesis of Myelodysplastic Syndromes

Paracatu, L. C. & Schuettpelz, L. G., Jun 17 2020, In : Frontiers in immunology. 11, 1236.

Research output: Contribution to journalReview article

Open Access
  • Open conformation of tetraspanins shapes interaction partner networks on cell membranes

    Yang, Y., Liu, X. R., Greenberg, Z. J., Zhou, F., He, P., Fan, L., Liu, S., Shen, G., Egawa, T., Gross, M. L., Schuettpelz, L. G. & Li, W., Sep 15 2020, In : EMBO Journal. 39, 18, e105246.

    Research output: Contribution to journalArticle

  • Pediatric acute lymphoblastic leukemia, version 2.2020

    Brown, P., Inaba, H., Annesley, C., Beck, J., Colace, S., Dallas, M., DeSantes, K., Kelly, K., Kitko, C., Lacayo, N., Larrier, N., Maese, L., Mahadeo, K., Nanda, R., Nardi, V., Rodriguez, V., Rossoff, J., Schuettpelz, L., Silverman, L., Sun, J. & 6 others, Sun, W., Teachey, D., Wong, V., Yanik, G., Johnson-Chilla, A. & Ogba, N., Jan 1 2020, In : JNCCN Journal of the National Comprehensive Cancer Network. 18, 1, p. 81-112 32 p.

    Research output: Contribution to journalReview article

    Open Access
  • 4 Scopus citations

    The tetraspanin CD53 regulates early B cell development by promoting IL-7R signaling

    Greenberg, Z. J., Monlish, D. A., Bartnett, R. L., Yang, Y., Shen, G., Li, W., Bednarski, J. J. & Schuettpelz, L. G., Jan 1 2020, In : Journal of Immunology. 204, 1, p. 58-67 10 p.

    Research output: Contribution to journalArticle

    Open Access
  • 6 Scopus citations

    TLR2/6 signaling promotes the expansion of premalignant hematopoietic stem and progenitor cells in the NUP98–HOXD13 mouse model of MDS

    Monlish, D. A., Greenberg, Z. J., Bhatt, S., Leonard, K. M., Romine, M. P., Dong, Q., Bendesky, L., Duncavage, E., Magee, J. A. & Schuettpelz, L., 2020, (Accepted/In press) In : Experimental Hematology.

    Research output: Contribution to journalArticle

    Open Access