RESEARCH FOCUS: Pharmacological targeting of Metastatic Breast Cancer
Research in our lab is focused on understanding and targeting the molecular mechanisms necessary for cancer cells to exit the primary tumor environment, metastasize and acquire resistance to currently used targeted molecular therapies. 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 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. 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. Global gene expression 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 the lab utilizes genetic and pharmacologic manipulation of several potential resistance mediators to validate their role in eliciting EMT and the 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 our research has a directed focus on utilizing in vivo optical imaging to track and quantify cell number, location and specific activation of particular signaling pathways.
SUPPORT BREAST CANCER RESEARCH
IN THE WENDT LAB:
To support research happening in the Wendt lab gifts can be made to the Purdue Research foundation with a note indicating funds should be directed to the Lab of Dr. Michael Wendt. Gifts can be mailed to:
Purdue University Center for Cancer Research
Hansen Life Sciences Building
201 S. University St
West Lafayette IN 47907
Please contact Dr. Wendt or Tim Bobillo (765-496-6374) to learn more about directly supporting cancer research at Purdue.
May 2019 - Welcome to Mitchell Ayers, a new graduate student in the Wendt lab!
April 2019 - Spleen Tyrosine Kinase-Mediated Autophagy Is Required for Epithelial-Mesenchymal Plasticity and Metastasis; was published and selected for the cover of Cancer Research! Congrats Aparna! Read the commentary here.
February 2019 - We received an R01 from the NCI on our work on metabolic plasticity in metastasis. Thanks you for the support!
January 2019 - We received the Translational Research Award from METavivor! Thank you for the support!
January 2019 - Welcome to Sherry Liang and Sebastian Paez, two new graduate students in the Wendt lab!
September 2018 - Biased signaling downstream of epidermal growth factor receptor regulates proliferative versus apoptotic response to ligand; was published in Cell Death and Disease. Congrats Remah!
June 2018 - Autocrine Fibronectin Inhibits Breast Cancer Metastasis; was published and was selected for the cover of Molecular Cancer Research. Congrats Aparna!