Interdisciplinary Life Science - PULSe Great research is a matter of choice

Michael Wendt

Michael Wendt Profile Picture

Assistant Professor
Ph.D. Medical College of Wisconsin 2007


Contact Info:

mwendt@purdue.edu


Training Group(s):
Immunology and Infectious Diseases
Molecular Signaling and Cancer Biology


Current Research Interests:

Research in my lab is focused on understanding and targeting the molecular mechanisms whereby cancer cells exit the primary tumor environment, metastasize and acquire resistance to targeted molecular therapies. Indeed, the future of personalized medicine lies in the successful application of therapeutics that target very specific aspects of cancer cell biology. Given their specificity is not surprising that while several targeted therapies are initially quite effective, metastatic tumor recurrence and therapeutic resistance remain major clinical problems. A critical aspect of metastasis and drug resistance is the process of epithelial-mesenchymal transition (EMT). EMT is a highly complex process whereby normal epithelial cells can temporarily take on characteristics of more motile and fibroblastoid like cells to facilitate developmental processes and wound repair. Cancer cells aberrantly utilize this process during the tumor invasion and metastasis, and more recently EMT has been linked to acquisition of a stem-cell phenotype and drug resistance. Recent work by our laboratory has depicted critical roles for EMT in primary tumor exit and initiation of outgrowth at the metastatic destination. Furthermore, we have established that EMT plays a critical role in altering signaling processes emanating from ErbB1 (EGFR) and ErbB2 (Her2), two key molecules in breast cancer development. Indeed, these EMT-mediated events coalesce to elicit resistance to breast cancer therapies that target ErbB receptors. Understanding and overcoming how EMT facilitates resistance to ErbB-directed therapeutics is a major focus of our research. To approach this question we have established a number of unique cell lines that have undergone EMT and acquired resistance to agents targeting ErbB receptors and downstream effector molecules. Microarray analyses of these resistant cells have revealed several potential targets that may be responsible for the EMT process and more importantly therapeutic resistance. Ongoing work in my lab utilizes genetic and pharmacologic manipulation of several potential resistance mediators to validate their role in eliciting the EMT and drug resistant status of cancer cells. To address these questions we utilize approaches that include three-dimensional cell culture and in vivo mouse models of tumor growth and metastasis. In particular my research has a directed focus on utilizing in vivo bioluminescent imaging to track and quantify cell number, location and specific activation of particular signaling pathways.



Selected Publications:

Peer Reviewed Publications: * indicates coauthorship; † indicates corresponding author

Wendt MK †, Taylor MA, Schiemann BJ, Sossey-Alaoui K, Schiemann WP. FGFR splice variants are stable markers of oncogenic TGF-b signaling. Breast Cancer Research. 2014 Mar 16(2):R24

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. 

Parvani JG, Davuluri G, Wendt MK, Espinosa C, Tian M, Danielpour D, Sossey-Alaoui K, Schiemann WP. Deptor enhances triple-negative breast metastasis and chemoresistance through coupling to survivin expression. Neoplasia. 2015 March; 17(3): 317-328.

Wendt MK, Schiemann WP. Longitudinal Bioluminescent Quantification of Three Dimensional Cell Growth. Bio-Protocol. Epub Dec 5 2013.

Wendt MK, Schiemann BJ, Parvani JG, Lee YH, Kang Y, Schiemann WP. Pyk2 is part of an EMT program that drives the outgrowth of metastatic breast cancer . Oncogene. 2013 Apr 18;32(16):2005-15. Epub 2012 June 18th.

 Wendt MK, Molter J, Flask CA, Schiemann WP. In Vivo Dual Substrate Bioluminescent Imaging. Journal of Visualized Experiments. Epub 2011 October 11. pii: 3245. doi: 10.3791/3245.

Wendt MK, Taylor MA, Schiemann BJ, Schiemann WP. Downregulation of E-cad is required to initiate the outgrowth of metastatic breast cancer. MBC. 2011 Jul; 22(14): 2423-35. Epub 2011 May 25.

 Wendt MK, Smith JA, Schiemann WP. Transforming Growth Factor-beta-Induced Epithelial-Mesenchymal Transition Facilitates Oncogenic Epidermal Growth Factor Receptor Signaling in Breast Cancer, Oncogene. 2010, Dec 9; 29(49): 6485-98. Epub 2010 Aug 30. 

Wendt MK, Smith JA, Schiemann WP. p130Cas is required for mammary tumor growth and TGF-beta-mediated metastasis through regulation of Smad2/3 activity. Journal of Biological Chemistry, 2009 Dec; 284(49):34145-56. Epub 2009 Oct 12. 

Wendt MK, Schiemann WP.  Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-beta signaling and metastasis. Breast Cancer Research. 2009 Sep, 11(5):R68. 

 Wendt MK, Drury LD, Vongsa RA, Dwinell MB.  Constitutive CXCL12 expression induces anoikis in colorectal carcinoma cells. Gastroenterology. 2008 Aug;135(2):508-17. Epub 2008 May 15.

 Wendt MK, Johanesen PA, Kang-Decker N, Binion DG, Shah V, Dwinell MB.  Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis. Oncogene. 2006 Aug 17;25(36):4986-97. Epub 2006 Mar 27. 

Wendt MK, Allington TM, Schiemann WP.  Mechanisms of Epithelial-Mesenchymal Transition by TGF-beta. Future Oncology, 2009 Oct;5(8):1145-68.

Wendt MK*, Tian M*, Schiemann WP, Deconstructing the mechanisms and consequences of TGF-beta-induced EMT during cancer progression. CTR. Epub 2011 June 21.

Book Chapters:

Wendt MK, Allington TM, Schiemann WP.  Regulation of epithelial-mesenchymal transition by TGF-beta in normal and malignant cells. Human Epithelial Tumor Cell Plasticity: Implications for Cancer Progression and Metastasis.  2008: p.155-180 ISBN:978-81-308-0275-6 Editor:  Paul J. Higgins, PhD.

Wendt MK, Schiemann WP. Regulation of TGF-beta Signaling and Metastatic Progression by Tumor Microenvironments. Signaling Pathways and Molecular Mediators in Metastasis. 2011: p.115-141 ISBN 978-94-007-2557-7. Editor: Alessandro Fatatis.

Wendt MK, Schiemann WP. The Multifunctional Roles of TGF-beta in Navigating the Metastatic Cascade. TGF-beta in Human Disease. 2013 ISBN 978-4431544081. Editors: Aristidis Moustakas and Keiji Miyazawa.

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