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BIOMARKER IDENTIFICATION, THERAPY DISCOVERY AND TARGET VALIDATION
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Mechanisms of Cell State Plasticity within the Tumor Microenvironment

THE PROBLEM

The molecular and cellular heterogeneity within the tumor microenvironment regulates cancer initiation/progression and the development of resistance to targeted therapies. Notably, these mechanisms parallel those that prevent many tissues/organs from fully regenerating. By understanding how cell state plasticity drives cancer progression/relapse and/or prevents complete tissue regeneration, my laboratory (The Developmental Oncogene Lab) aims to develop novel tools and strategies to diagnose/treat cancer onset and progression.

THE APPROACH

During my training as a graduate student (with Wylie Vale) and postdoctoral fellow (with Richard Klemke), I characterized new TGFbeta signaling mechanisms and identified PEAK1 as a cytoskeleton-associated kinase required for pancreatic cancer progression. My independent research group at CSUN (established in 2012) has identified an essential role for PEAK1-dependent MAPK signaling as mediator of TGFbeta-induced EMT and cancer metastasis. In parallel, we have developed new biomarker identification methods (in collaboration with Claremont BioSolutions) and identified ITGA1 as a new diagnostic/therapeutic target for improving chemotherapy responsiveness and decreasing metastasis in pancreatic cancer. These recent contributions to cancer biology synergize with our current efforts aimed at identifying novel tumor cell vulnerabilities in complex cell systems and primary/metastatic tumors that are engaged in response to targeted therapies or microenvironment stress. My laboratory utilizes techniques involving cellular/molecular biology, widefield/confocal/TIRF microscopy, multiplexing IF, hydrogel scaffolds, 3D cultures, flow cytometry and vertebrate animals (mouse, chicken and fish). To support these research efforts, my lab has received extramural funding in total of >$1.76 M, including our recent R01-equivalent SC1 award (SC1GM121182).