• Source: Scopus
19992021

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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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