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. 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. 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 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 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.
10-17-17 - Regulation of epithelial-mesenchymal transition and metastasis by TGF-beta, P-bodies, and autophagy; was published in Oncotarget. Congrats Shana and Aparna!
9-15-17 - Selective inhibition of STAT3 phosphorylation using a nuclear-targeted kinase inhibitor; was published in ACS Chemical Biology. Congrats Wells and Remah!
9-1-17 - Remah Ali received the MCMP endowment award. Congrats Remah!
7-24-17 - Welcome to Hao Chen (graduate student) and Ammara Abdullah (postdoc), the newest members of the Wendt lab!
3-15-17 - The Wendt Lab has received a R01 grant from the National Cancer Institute. Thanks for the support!
1-10-17 - The paradoxical functions of EGFR during breast cancer progression; was published in Signal Transduction and Targeted Therapy. Congrats Remah!
11-16-16 - Hang Lin has joined the Wendt Lab as a graduate student. Welcome Hang!
11-4-16 - FGFR signaling maintains a drug persistent cell population following epithelial-mesenchymal transition; was published in Oncotarget!
9-27-16 - The Wendt Lab has received a Research Scholar Grant grant from the American Cancer Society. Thanks for the support!