Laura G. Schuettpelz, M.D., Ph.D.

Associate Professor
Pediatrics
Hematology/Oncology

Developmental, Regenerative and Stem Cell Biology Program
Immunology Program
Molecular Genetics and Genomics Program

  • 314-286-1813

  • schuettpelz_l@kids.wustl.edu

  • Regulation of hematopoietic stem cells (HSCs) by inflammation

Research Abstract:

The Schuettpelz Lab is interested in understanding how inflammatory signals regulate hematopoietic stem cells (HSCs). These signals (e.g., inflammatory cytokines, toll like receptor agonists) are important for normal immune system development and for shaping the response to acute infection or injury, however sustained inflammation causes a loss of normal HSC function leading to bone marrow suppression. Furthermore, inflammatory signals can promote the development of hematopoietic malignancies. Therefore, an understanding of how HSCs respond to such signals is important for the maintenance of healthy hematopoiesis, as well as for the prevention of blood cancers.

Current Projects:
-Role of toll like receptor (TLR) signaling in myelodysplastic syndromes. TLRs are pattern recognition receptors that are important for the normal immune system response to pathogens. Enhanced expression of TLRs and increased TLR signaling is associated with myelodysplastic syndromes (MDS), which are hematopoietic stem cell disorders characterized by ineffective hematopoiesis and a high risk of transformation to acute leukemia. Our lab is exploring the connection between enhanced TLR signaling and MDS through the use of primary patient samples and also various mouse models of this disease.

-Role of tetraspanins in hematopoiesis. Tetraspanins are a family of transmembrane proteins that are important for organizing the plasma membrane and regulating processes such as cellular migration, adhesion and activation. Loss of the tetraspanin family member CD53 is associated with recurrent infections in humans, however its role in hematopoiesis and the immune system is not well understood. We found that expression of CD53 is markedly upgregulated upon exposure of HSCs to inflammatory and mobilizing signals, and loss of CD53 leads to reduced HSC function in the face of inflammation. In addition, we have identified a critical role for CD53 in B cell development and trafficking. Ongoing experiments are aimed at further defining these roles for CD53 and elucidating the mechanisms by which it regulates these processes. Finally, malignant B cells have high CD53 expression, and we are therefore investigating CD53 as a potential therapeutic target in B-lineage malignancies

Mentorship and Commitment to Diversity Statement:
Our lab is small and collaborative, and all trainees are expected to contribute to the rich learning environment within the lab and among our larger group of collaborators. I tailor my mentorship style to the needs of each trainee, understanding that those needs evolve based on prior training, experience and goals. I am actively involved in the day-to-day workings of the lab, and have regular 1:1 meetings with each trainee (in addition to weekly group meetings and bi-weekly multi-lab meetings). Trainees are encouraged to develop new ideas, and are given ample freedom to work independently as their abilities dictate. I am always available to provide feedback and guidance, and place a very high priority on the career development of my trainees. I work with each of my trainees to define career goals, and to acquire the skills (e.g., technical skills, mentorship of students, paper and grant writing, presentations at local and national/international meetings) to achieve those goals. Trainees in my lab interact with collaborators throughout the campus, and are expected to present their work at local and national/international meetings to facilitate networking and collaboration.

Selected Publications:

Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, et al. Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain-of-function. Blood. 2020.

Monlish DA, Greenberg ZJ, Bhatt ST, Leonard KM, Romine MP, Dong Q, et al. TLR2/6 signaling promotes the expansion of premalignant hematopoietic stem and progenitor cells in the NUP98-HOXD13 mouse model of MDS. Experimental hematology. 2020;88:42-55.

Paracatu LC, Schuettpelz LG. Contribution of Aberrant Toll Like Receptor Signaling to the Pathogenesis of Myelodysplastic Syndromes. Frontiers in immunology. 2020;11:1236.

Greenberg ZJ, Monlish DA, Bartnett RL, Yang Y, Shen G, Li W, et al. The Tetraspanin CD53 Regulates Early B Cell Development by Promoting IL-7R Signaling. Journal of immunology. 2020;204(1):58-67.

Monlish DA, Bhatt ST, Duncavage EJ, Greenberg ZJ, Keller JL, Romine MP, et al. Loss of Toll-like receptor 2 results in accelerated leukemogenesis in the NUP98-HOXD13 mouse model of MDS. Blood. 2018;131(9):1032-5.

Herman AC, Monlish DA, Romine MP, Bhatt ST, Zippel S, Schuettpelz LG. Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms. Blood Cancer J. 2016;6:e437.

Monlish DA, Bhatt ST, Schuettpelz LG. The Role of Toll-Like Receptors in Hematopoietic Malignancies. Frontiers in immunology. 2016;7:390.

Schuettpelz LG, Borgerding JN, Christopher MJ, Gopalan PK, Romine MP, Herman AC, et al. G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling. Leukemia. 2014.

Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 2013;495(7440):227-30.

Schuettpelz LG, Link DC. Regulation of hematopoietic stem cell activity by inflammation. Frontiers in immunology. 2013;4:204.

Schuettpelz LG, Gopalan PK, Giuste FO, Romine MP, van Os R, Link DC. Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function. Blood. 2012;120(15):2981-9.

Last Updated: 3/31/2021 8:39:22 AM

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