Kathryn Schwertfeger

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Credentials

PhD

Research Summary

Dr. Schwertfeger is a member of the Division of Molecular Pathology and Genomics.  Her main research effort is focused on the breast cancer microenvironment and how breast cancers cells interact with cells in the stroma, particularly with immune cells. The cell of particular interest to her group is the macrophage, a specialized innate immune system cell. Macrophages circulate as monocytes in the blood and are recruited to different tissue sites as part of an immune response. Macrophages have long been known to be associated with tumors, initially it was thought to attack tumors. More recently scientists have found that macrophage populations at a tumor site is reflective of tumor size and aggressiveness, suggesting the possibility that macrophages may serve to promote tumor growth rather than attacking tumors. It is now understood that macrophages are recruited by tumors through signaling mechanisms and commandeered to assist in tumor expansion and metastasis.

Schwertfeger and her colleagues are interested in the mechanisms that drive macrophage-tumor cell interactions and the internal signaling in macrophages that causes them to respond the way they do in the tumor microenvironment. If signaling mechanisms can be identified, they could be targets for therapeutic intervention. Macrophages, literally "big eaters," are large cells that normally engulf and digest cellular debris and foreign material and could potentially be turned against the tumor. Researchers have tended to focus on the soluble growth factors macrophages produce as part of their normal functions rather than signaling pathways that could reveal how and why they produce these factors. Schwertfeger's team is currently exploring three macrophage signaling molecules involved in normal macrophage functioning and that of other cell types. They include two transcriptions factors, STAT3 and STAT5, and the cell-surface enzyme ADAM17, which is involved in a spectrum of regulatory activities that includes cleaving of cell-surface-bound growth factors, freeing them to carry out their cellular functions. Schwertfeger and her colleagues have found that activation of the fibroblast growth factor receptor (FGFR)-STAT3 pathway induces accumulation of the extracellular matrix carbohydrate hyaluronan, which promotes tumor proliferation and migration. Although drugs targeting STAT transcription factors or ADAM17 enzymes are plausible, how inhibiting these pathways would affect immune system function in healthy and tumor tissue is unknown and is a related research interest of Schwertfeger's laboratory.  

Schwertfeger's laboratory is also exploring how breast cancer cells interact with osteoclasts to promote bone metastasis using the FGFR signaling pathway. The research is aimed at determining whether the pathway is important in the ability of breast cancer cells to activate osteoclasts, initiate bone degradation and form osteolytic breast cancer lesions. The FGFR pathway can be targeted, with a number of inhibitors currently in clinical trials for treating primary tumors but not metastasis. Schwertfeger's goal is to see whether the FGFR pathway inhibitors can be used to inhibit breast cancer metastasis._ _Member, American Association for Cancer Research (AACR) NIH/NCI Grant Review Panel: Member of Tumor MicroEnvironment study sectionJournal of Mammary Gland Biology and Neoplasia - Editorial Board MemberBreast Cancer Research - Associate Editor

Publications

• Bapat AS, O'Connor CH, Schwertfeger KL. Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors. Sci Rep. 2023 Apr 1;13(1):5349. doi: 10.1038/s41598-023-32321-0
• Tarullo SE, He Y, Daughters C, Knutson TP, Henzler CM, Price MA, Shanley R, Witschen P, Tolg C, Kaspar RE, Hallstrom C, Gittsovich L, Sulciner ML, Zhang X, Forster CL, Lange CA, Shats O, Desler M, Cowan KH, Yee D, Schwertfeger KL, Turley EA, McCarthy JB, and Nelson AC.  Receptor for hyaluronan-mediated motility (RHAMM) defines an invasive niche associated with tumor progression and predicts poor outcomes in breast cancer patients. The Journal of Pathology. First published: 26 April 2023  https://doi.org/10.1002/path.6082.  Note: This research was supported in part by the LMP initiative in spatial 'omics. 
• Witschen PM, Chaffee TS, Brady NJ, Huggins DN, Knutson TP, LaRue RS, Munro SA, Tiegs L, McCarthy JB, Nelson AC, Schwertfeger KL. Tumor cell-associated hyaluronan-CD44 signaling promotes pro-tumor inflammation in breast cancer. Cancers 2020, 12, 1325. https://doi.org/10.3390/cancers12051325. 
• Irey EA, Lassiter CM, Brady NJ, Chuntova P, Wang Y, Knutson TP, Henzler C, Chaffee TS, Vogel RI, Nelson AC, Farrar MA, Schwertfeger KL. JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors. Proc Natl Acad Sci U S A. 2019 May 30. pii: 201816410. doi: 10.1073/pnas.1816410116. 
• Nelson AC, Machado HL, Schwertfeger KL. Breaking through to the other side: Microenvironment contributions to DCIS initiation and progression. J Mammary Gland Biol Neoplasia. 2018 Aug 31. doi: 10.1007/s10911-018-9409-z. 
• Farooqui, M., Bohrer, L.R., Brady, N.J., Chuntova, P., Kemp, S.E., Wardwell, C.T., Nelson, A.C. and Schwertfeger, K.L. Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival. Molecular Cancer. 14(138), 2015. PMID: 26215578.