Michael K. Wendt
Ph.D. - 2007 Medical College of Wisconsin (Molecular Genetics)
Postdoc - 2007-2010 University of Colorado (Pharmacology)
Postdoc - 2010-2013 Case Western Reserve University (General Medical Sciences (Oncology)).
Research in the Wendt lab focuses on pharmacological targeting of molecular players involved in the metastatic outgrowth of breast cancer. Systemic dissemination is an extremely early event in breast cancer progression, therefore we primarily focus on developing strategies that are specifically designed to target secondary tumors. We take two major approaches to this challenge:
1.Through metastatic progression breast cancer cells under epithelial-mesenchymal transition (EMT) and reverse process of mesenchymal-epithelial transition (MET). An overriding hypothesis in the lab is that through the processes of EMT:MET the secondary epithelial state that characterizes the metastatic tumor is fundamentally unique from the epithelial status of the primary tumors. We believe these differences hold the keys to developing therapeutics capable of pharmacologically treating metastatic lesions.
2.Subsequent to dissemination, a large fraction of tumor cells enter into an asymptomatic state of dormancy. The ability of normal organs to resist tumor secondary tumor formation is the body’s last defense against metastatic disease progression. The environmental factors (drugs, alcohol, diet, etc…) capable of “awaking” disseminated cells are poorly characterized. Understanding these factors is required if we hope to design therapeutics and other interventions capable of maintaining systemic tumor dormancy.
Approaches: Ongoing work in my lab utilizes bioinformatics, genetics and pharmacologic approaches to validate the role of molecules in eliciting EMT and drug resistance in cancer cells. To address these questions we utilize several in vitro imaging techniques in conjunction with three-dimensional cell culture and in vivo mouse models of tumor growth and metastasis. In particular our lab has a directed focus on utilizing in vivo bioluminescent imaging to track and quantify cell number, location and activation of particular signaling pathways. We are always looking for productive collaborations!
Coleman MF, Kuloylouoglu Cotul E, Pfeil AJ, Devericks EN, Chen H, Kiesel VA, Safdar MH, Teegarden, D, Hursting SD, Wendt MK. Hypoxia-mediated suppression of pyruvate carboxylase drives tumor microenvironment immunosuppression. 2023. BioRxiv. doi: https://doi.org/10.1101/2022.04.06.487050
Chen H, Cresswell G, Libring S, Ayers M, Miao J, Zhang ZY, Solorio L, Ratliff T, Wendt MK. Tumor-cell autonomous SHP2 contributes to immune suppression in metastatic breast cancer. Cancer Research Communications. (2022) 2 (10): 1104–1118
Shinde A, Kulkoyluoglu Cotul E, Chen H, Smith A, Libring S, Solorio L, Wendt MK. Transglutaminase-2 mediates acquisition of neratinib resistance in metastatic breast cancer. 2022. Mol Biomed, Jun 22; 3(1):19.
Akhand SA, Purdy SC, Liu Z, Anderson JC, Willey CD, Wendt MK. Fibroblast growth factor receptor facilitates recurrence of minimal residual disease following trastuzumab emtansine therapy. NPJ Breast Cancer, Jan 21st (2021).
Chen H, Libring S, Viswanatharaju Ruddraraju K, Miao K, Solorio L, Zhang ZY, Wendt MK. SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer. Oncogene. Oct 8, 2020
Akhand SA, Liu Z, Purdy SC, Abdullah A, Lin H, Cresswell G, Ratliff T, Wendt MK. Pharmacological inhibition of FGFR modulates the metastatic immune microenvironment and promotes response to checkpoint blockade. Cancer Research Immunology. Oct 22nd 2020.
Abdullah A, Akhand SA, Paez JS, Brown W, Pan L, Libring S, Badamy M, Dykhuizen E, Solorio L, Tao WA, Wendt MK. Epigenetic targeting of neuropilin-1 prevents bypass signaling in drug resistant breast cancer. Oncogene. Oct 30th (2020).
Shinde A, Hardy SD, Kim D, Salehin Akhand S, Jolly MK, Wang W, Anderson JC, Khodadadi RB, Brown WS, George JT , Liu S, Wan J, Levine H, Willey CD, Krusemark CJ, Geahlen RL, Wendt MK. Spleen tyrosine kinase-mediated autophagy is required for epithelial-mesenchymal plasticity and breast cancer metastasis. Cancer Research, 2019 Apr 15;79(8):1831-1843.
Ali R, Brown W, Purdy SC, Davisson VJ, Wendt MK. Biased signaling downstream of epidermal growth factor receptor regulates proliferative versus apoptotic response to ligand. Cell Death and Disease, 9:976 (2018)
Shinde A, Wilmanski T, Chen H, Teegarden D, Wendt MK. Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer. Breast Cancer Research. 2018. 20:76.
Shinde A, Alpsoy A, Abdullah A, Schaber J, Solorio L, Wendt MK. Autocrine fibronectin inhibits breast cancer metastasis. Molecular Cancer Research, doi: 10.1158/1541-7786.MCR-18-0151
Bartolowits MD, Brown W, Ali R, Pedley AM, Chen Q, Harvey KE, Wendt MK, Davisson VJ. Selective inhibition of STAT3 phosphorylation using a nuclear-targeted kinase inhibitor. ACS Chem Biol. Epub Aug 18 2017.
Brown WS, Akhand SS, Wendt MK. FGFR signaling maintains a drug persistent state following induction of epithelial-mesenchymal transition. Oncotarget. Epub Nov 4 2016.
Brown WS, Tan L, Smith A, Gray NS, Wendt MK. Covalent targeting of fibroblast growth factor receptor inhibits metastatic breast cancer. Molecular Cancer Therapeutics. Epub July 1 2016.
Wendt MK †, Williams WK, Pascuzzi PE, Balanis NG, Schiemann BJ, Carlin CR, Schiemann WP. The antitumorigenic function of EGFR in metastatic breast cancer is regulated by expression of Mig6. Neoplasia. 2015 Jan; 17(1): 124-133.
Wendt MK †, Molly A. Taylor, Schiemann BJ, Khalid Sossey-Alaoui, Schiemann WP. FGFR splice variants are stable markers of oncogenic TGF-beta signaling in metastatic breast cancer.Breast Cancer Research. 2014 Mar 11;16(2):R24.
Kiesel VA, Sheeley MP, Coleman MF, Cotul EK, Donkin SS, Hursting SD, Wendt MK, Teegarden D. Pyruvate carboxylase and cancer progression. Cancer and Metabolism. 9:20 (2021).
Ali RA, Wendt MK. The paradoxical functions of EGFR during breast cancer progression. Signal transduction and targeted therapy. 2017. doi:10.1038/sigtrans.2016.42. Epub 2017 Jan 20.
Brown WS, Wendt MK. Integrin-mediated resistance to epidermal growth factor receptor-targeted therapy: an inflammatory situation. Breast Cancer Research. 2014. Sept. 16(5):448.
Ali RA, Akhand SS, Wendt MK. Targeting FGFR for the treatment of breast cancer. Resistance to Targeted Therapies in Breast cancer. 2017 Editor: Jenifer Prosperi. https://link.springer.com/chapter/10.1007/978-3-319-70142-4_5#enumeration