Project Grant 2145521

CAREER: IN VITRO MODEL APPROACHES LEVERAGING QUANTITATIVE CANCER CELL PROPERTIES AS DETERMINANTS OF METASTATIC POTENTIAL -CANCER METASTASIS OCCURS WHEN TUMOR CELLS BREAK AWAY FROM THE ORIGINAL TUMOR AND MOVE, OR SPREAD TO OTHER PARTS OF THE BODY. IN THE CASE OF BREAST CANCER, THE MAJORITY OF PATIENT DEATHS ARE AS A RESULT OF METASTASIS TO OTHER PARTS OF THE BODY, INCLUDING BONES, LUNG, AND BRAIN. THUS, IT IS IMPORTANT TO IDENTIFY CELLS THAT HAVE THE POTENTIAL TO BE METASTATIC CELLS EARLY AND RELIABLY. THIS CAREER PROPOSAL AIMS TO DEVELOP NOVEL STRATEGIES BASED ON MEASURING QUANTITATIVE PROPERTIES OF CANCER CELLS TO BETTER UNDERSTAND WHAT CONTRIBUTES TO METASTATIC CANCER AND WHAT SPECIFIC SIGNATURE METASTATIC CELLS HAVE THAT DISTINGUISHES THEM FROM NON-METASTATIC CELLS. THE PROPOSED WORK INTEGRATES A COMPREHENSIVE EDUCATION PLAN FOR MEETING THE PRIMARY OBJECTIVE OF INCREASING THE PARTICIPATION OF UNDERREPRESENTED MINORITIES IN BIOMEDICAL ENGINEERING. THIS PLAN WILL FOSTER AWARENESS AND INTEREST IN BIOMEDICAL ENGINEERING AND RESEARCH THROUGH RESEARCH MENTORING AND PROGRAMMING DEVELOPED TO PROVIDE EARLY AWARENESS OF BIOMEDICAL CAREER PATHS FOR STUDENTS. IN ADDITION, EDUCATIONAL OUTREACH EVENTS FOR ALL LEVELS WILL BE IMPLEMENTED, INCLUDING INITIATIVES FOR K-12 AND COLLEGE STUDENTS, AS WELL AS COMMUNITY-FOCUSED HEALTH & OUTREACH DAYS. THE INVESTIGATOR'S LONG-TERM RESEARCH GOAL IS TO DEVELOP STRATEGIES AND TOOLS THAT WILL HELP TO BETTER UNDERSTAND THE ROLE OF THE TUMOR MICROENVIRONMENT IN CANCER METASTASIS, WHICH WILL LEAD TO IMPROVED HEALTH OUTCOMES FOR PATIENTS WITH METASTATIC CANCER. TO MAKE SIGNIFICANT POSITIVE CONTRIBUTIONS TO CLINICAL OUTCOMES, IT IS NECESSARY TO FIRST HAVE A BETTER FUNDAMENTAL UNDERSTANDING OF CANCER CELL PROCESSES AND THE EFFECTS OF SPECIFIC FACTORS FROM THE TUMOR MICROENVIRONMENT ON CANCER CELL BEHAVIOR TO IDENTIFY METASTATIC CELLS EARLIER AND MORE RELIABLY. TOWARDS THIS GOAL, THIS CAREER PROJECT PRIMARILY FOCUSES ON UNDERSTANDING CONTRIBUTORS TO CANCER CELL METASTASIS, WITH A SPECIFIC FOCUS ON THE ROLE OF THE EXTRACELLULAR MATRIX (ECM) AND ADIPOSE-SECRETED FACTORS. THE RESEARCH OBJECTIVES OF THIS CAREER PROPOSAL ARE AIMED AT TESTING THE HYPOTHESIS THAT BREAST CANCER CELLS HAVE INHERENT PHENOTYPICAL CHARACTERISTICS ASSOCIATED WITH IMPEDANCE, MORPHOLOGY, AND GENE/PROTEIN EXPRESSION, WHICH DISTINGUISH METASTATIC CELLS FROM NON-METASTATIC CELLS. SPECIFICALLY, THE AIMS OF THIS WORK WILL: 1) ASSESS THE IMPEDANCE PROFILES FOR BREAST CANCER CELLS OF VARYING TYPE TO IDENTIFY DISTINCT IMPEDANCE SIGNATURES FOR SPECIFIC CELL TYPES; 2) IDENTIFY MORPHOLOGICAL FEATURES ASSOCIATED WITH BREAST CANCER CELL METASTASIS BY QUANTIFYING CHANGES IN CELL SHAPE; AND 3) ASSESS THE EFFECTS OF CYTOKINES ON BREAST CANCER METASTASIS USING IMPEDANCE AND MORPHOLOGY-BASED ANALYSES. QUANTITATIVE IN VITRO MODELING APPROACHES WILL BE APPLIED TO OBTAIN QUANTITATIVE DATA THAT WILL BE USED TO DELINEATE THE SPECIFIC SIGNATURE OF METASTATIC CANCER CELLS. DETERMINATION OF SPECIFIC CHARACTERISTICS USEFUL FOR IDENTIFYING METASTATIC CANCER CELLS WILL HAVE FAR-REACHING IMPACT FOR ADVANCING FUTURE CANCER RESEARCH AND CLINICAL APPLICATIONS. INTEGRATED INTO THIS WORK IS A COMPREHENSIVE EDUCATIONAL PLAN TOWARDS MEETING THE PI?S LONG-TERM EDUCATIONAL GOAL OF INCREASING SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AWARENESS AND PARTICIPATION OF UNDERREPRESENTED MINORITIES IN BIOMEDICAL RESEARCH AND CAREER PATHS. SPECIFIC EDUCATIONAL OBJECTIVES ARE TO: 1) PROMOTE STEM AND HEALTH AWARENESS THROUGH EDUCATIONAL AND COMMUNITY OUTREACH ACROSS GENERATIONS, FROM K-12 THROUGH GRAY POPULATIONS; AND 2) SUPPORT CROSS-DISCIPLINARY RESEARCH MENTORSHIP AND PROGRAMMING AT ALL LEVELS TO INCREASE THE NUMBER OF UNDERREPRESENTED MINORITY STUDENTS PURSUING GRADUATE DEGREES IN BIOMEDICAL ENGINEERING. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.