Charles M. LeVea

Research Overview:

My research has elucidated molecular mechanisms underlying the pathogenesis and progression of various cancers, leading to advances in diagnosis, prognostication, and treatment. Through genomic, proteomic, and functional analyses, we have identified prognostic biomarkers and therapeutic targets in cholangiocarcinoma, breast cancer, colon cancer, and pancreatic cancer.
Notable findings from our work include:
• Discovery of nuclear survivin expression as a marker of poor prognosis in cholangiocarcinoma.
• Identification of CD24 as an independent negative prognostic marker in cholangiocarcinoma.
• Demonstration that protein tyrosine phosphatase LAR expression correlates with metastatic potential in breast cancer.
• Elucidation of the cooperative roles of EGFR and TGF-beta signaling in colon cancer metastasis and organotropism utilizing orthotopic mouse models.
• Identification of the FGFR inhibitor, dovitinib, as a promising targeted therapy for pancreatic cancers with high FGFR expression.
In addition, our research has advanced pathological classification and prognostic information for various cancers. We have demonstrated the prognostic significance of evaluating depth of tumor invasion in colorectal cancer and showed depth of muscularis propria invasion does not impact esophageal adenocarcinoma outcomes. We have also worked to improve characterization of rare gallbladder cancer subtypes and premalignant lesions.
Key publications have elucidated the synergistic interaction between EGFR and neu in cell transformation, established methods to express and purify neu-encoded tyrosine kinase, revealed differences between proto-oncogenic and oncogenic neu receptors, elucidated heterodimerization requirements between EGFR and neu, and showed ligand-driven neu multimerization activates kinase signaling. These studies have provided important insights into receptor tyrosine kinase structure, function, activation, and contributions to oncogenesis.
Currently, we are investigating one’s genetic susceptibility to develop Barrett's esophagus, and, for those that do develop Barrett’s esophagus, their risk for progression to esophageal adenocarcinoma. I serve as the Roswell Park site PI and co-investigator on these projects. In a separate project, we are investigating the effect of antidepressant medications on the tumor microenvironment and survival in pancreatic cancer.
In summary, my multifaceted research program has provided important insights into the molecular underpinnings of cancer while also furthering biological understanding, diagnosis, staging, and treatment. Our findings have elucidated key oncogenic mechanisms, identified clinically useful prognostic markers, and uncovered novel therapeutic targets. This body of work has the potential to translate into direct improvements in the clinical management of cancer patients and prevention of cancer.