Cancer Invasion and Metastasis

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PROJECT SUMMARY/ABSTRACT The Cancer Invasion and Metastasis Program (CIM) is a new Program within the Sidney Kimmel Comprehensive Cancer Center (SKCCC). CIM was launched to elucidate and target the mechanisms driving metastasis, as metastasis is the major driver of patient outcomes. The Program consists of highly accomplished basic scientists working collaboratively with engineers and translational physician-scientists. The Co-Leaders are Andrew Ewald, Ph.D. (basic, invasion focused); Ashani Weeraratna, Ph.D. (basic, tumor microenvironment focused); and Phuoc Tran, M.D., Ph.D (basic/clinical, recurrent disease focused). CIM is comprised of 42 Members (31 Full Members and eleven Associate Members) from three schools and 16 departments at Johns Hopkins University. Faculty are affiliated with four T-32 training grants across the School of Medicine, School of Public Health, and School of Engineering. The total direct cancer-relevant peer- reviewed funding is $14.1 million, with $8.3 million from the National Cancer Institute. The total number of publications by Program members is 768, of which 129 (16.8%) are Intra-Programmatic, 412 (53.8%) are Inter- Programmatic and 487 (63.4%) have external collaborations. Of these publications, 20.6% are in journals with impact factors >10 and 5.7% in journals with impact factors >25. The Aims of the Program are: Aim 1: To elucidate the molecular and cellular mechanisms regulating individual and collective cancer cell motility and invasion across organ sites using cutting-edge models and tools. Aim 2: To define the regulation of cancer function by the cellular, molecular and mechanical features of the tumor microenvironment. Investigators target and disrupt the crosstalk between the cancer cell and the metastasis-promoting microenvironment using physiologically relevant models (e.g., organoids, 3D skin reconstruction, cell-derived matrices, humanized animal models). Aim 3: To determine and disrupt the underlying cause of recurrent cancer at the cellular and molecular level by targeting barriers to therapeutic success in cancer, including therapy resistance, tumor dormancy and recurrent disease. Research success across these aims is critically enabled by SKCCC Shared Resources (Oncology Tissue and Imaging Services, Experimental and Computational Genomics, Flow/Mass Cytometry and Technology Development, and Mass Spectrometry Molecular Imaging and Multi-Omics). Program members lead a P01 grant to understand microenvironmental regulation of therapy resistance and metastasis in melanoma, and a U54 that integrates physical science and translational perspectives to understand cancer invasion. Members also participate in three SPOREs (Prostate, GI, Head and Neck) and six MPI U01 grants.