Project Description

The majority of breast cancer related deaths occur as a result of metastasis. Once the cancer cells metastasize, the 5-year relative survival rate for breast cancer patients drastically drops. During metastasis, a complex series of events is initiated by changes in the extracellular matrix (ECM) composition and architecture in distant tissues, where the metastatic cancer cells take root and form secondary tumors. These distinct changes in the premetastatic niche (PMN) facilitate tumor cell colonization, phenotypic heterogeneity of the cell population, and contribute to drug resistance frequently observed in metastatic tumors. Using an engineered model of the PMN, we have demonstrated that extracellular vesicles (EVs) facilitate dynamic changes in premetastatic tissues, and that blocking key events during PMN formation disrupts the metastasis. Fundamental gaps remain in identifying critical events within the niche that facilitate metastatic colonization of tumor cells, cellular plasticity, and drug resistance. By targeting these events, metastasis can be disrupted, eliminating the most lethal aspect of breast cancer. The overall goal of this proposal is to develop treatment strategies designed to effectively target the premetastatic niche, disrupting critical ECM changes that make the distant tissues hospitable to metastatic cancer cells.

Start Date

Feb 2022

Postdoctoral Qualifications

The ideal candidates will be creative, curious, collaborative and highly motivated. Experience in proteomics, tissue culture, cell-based assays, basic molecular biology techniques (such as protein extraction and quantification), and confocal microscopy are highly desired. Other skills include the development and discovery of new methodologies and validation of the existing approaches for cancer therapy. Experience with executing in vivo studies involving the handling, care and use of laboratory animals and surgical procedures related to tumor inoculation and therapy are desirable.

Co-Advisors

Luis Solorio, lsolorio@purdue.edu, Weldon School of Biomedical Engineering, https://soloriolab.wixsite.com/tmet

Mike Wendt, mwendt@purdue.edu, Medicinal Chemistry and Molecular Pharmacology,
https://www.wendtlab.com

Bibliography

Enriquez, A.*, Libring, S.*, Field, T.C., Jimenez, J., Lee, T., Park, H., Satoski, D., Wendt, M.K., Calve, S., Tepole, A.B., Solorio, L., Lee, H. High-Throughput Magnetic Actuation Platform for Evaluating the Effect of Mechanical Force on 3D Tumor Microenvironment. Advanced Functional Materials. September 2020.

Libring, S.*, Shinde, A.*, Chanda, M.K., Nuru, M., George, H., Saleh, A.M., Abdullah, A., Kinzer-Ursem, T.L., Calve, S., Wendt, M.K., Solorio, L. The Dynamic Relationship of Breast Cancer Cells and Fibroblasts in Fibronectin Accumulation at Primary and Metastatic Tumor Sites. Cancers. May 2020.

Shinde, A., Paez, J.S., Libring, S., Hopkins, K., Solorio, L., Wendt, M. Transglutaminase-2 Facilitates Extracellular Vesicle-Mediated Establishment of the Metastatic Niche. Oncogenesis. February 2020.

Shinde, A., Libring, S., Alpsoy, A., Abdullah, A., Schaber, J., Solorio, L., Wendt, M. Autocrine Fibronectin Inhibits Breast Cancer Metastasis. Molecular Cancer Research. June 2018.

Chen, H., Libring, S., Ruddraraju, K.V., Miao, J., Solorio, L., Zhang, Z., Wendt, M.K. SHP2 is a Multifunctional Therapeutic Target in Drug Resistant Metastatic Breast Cancer. Oncogene. October 2020.