Cancers Treated:
Specializing In:
- Surgical pathology
- Gastrointestinal pathologist
- GI Biomarker discovery and validation
- Molecular alterations in gastrointestinal cancers
Research Interests:
- Receptor tyrosine phosphatase and tyrosine kinase structure, function, activation, and contributions to oncogenesis
- Pathological classification and prognostic information for various GI cancers
- Pathogenesis and progression of various GI cancers and identification of biomarkers for therapeutic targeted therapies
- Targeted therapy for pancreatic cancer
- Effect of antidepressant medications on tumor microenvironment and survival outcomes in pancreatic cancer
- Genetic susceptibility to Barrett's esophagus and risk prediction for progression to esophageal adenocarcinoma
Biography
I am a surgical pathologist and gastrointestinal (GI) pathology subspecialist. I joined the faculty at Roswell Park Comprehensive Cancer Center in 2003 and have spent my entire career at this outstanding cancer center. I served as Chair of the Department of Pathology & Laboratory Medicine from 2017-2021. In this role, I oversaw clinical, research, educational, business operations for a department of over 240 staff. As a leader, I championed advancement of the latest technologies, recruitment of diverse faculty, and alignment with institutional goals. As a pathologist, I have expertise in the diagnosis and subtyping of gastrointestinal tract cancers and pancreatic neoplasms.
Accurate cancer diagnosis guides treatment decisions and is essential for patient care. I direct our Gastrointestinal Pathology subspecialty group, participate in GI tumor boards, and provide expert second opinion consults. I have a passion for resident and fellow education, with prior experience of directing our oncologic surgical pathology fellowship training program for over a decade. I continue to mentor trainees and am honored to be part of the next generation's training.
My clinical passion is to care for cancer patients by providing accurate and timely diagnoses. My research interests include biomarkers of progression and prognosis in GI cancers. I have co-authored over 70 peer-reviewed publications on prognostic gene expression profiles, immunohistochemical markers, and understanding the tumor immune microenvironment. Recently, my work is examining molecular changes in the progression from Barrett's esophagus to esophageal adenocarcinoma. My goal is to identify biomarkers that can guide clinical decision making and lead to improvements in patient care.
I have a track record of productive research collaborations with clinicians and basic scientists at Roswell Park. I serve as co-investigator on many clinical trials, providing pathology analysis. My work has been supported by federal grants. I plan to continue pursuing impactful translational research in GI oncology. I am honored to contribute to Roswell Park's mission of understanding, preventing, and curing cancer.
Positions
Roswell Park Comprehensive Cancer Center
- Professor of Oncology
- Department of Pathology & Laboratory Medicine
Background
Education and Training
- 1996 - MD - State University of New York at Stony Brook, Brookhaven, NY
- 1992 - PhD - Experimental Pathology, University of Pennsylvania, Philadelphia, PA
- 1987 - MS - University of Rochester, Rochester, NY
Residency
- 1996-2000 - Anatomic & Clinical Pathology, University of Rochester, Rochester, NY
Fellowship
- 2000-2003 - Wilmot Fellowship, EGFR Signaling & Surgical Pathology, University of Rochester, Rochester, NY
Board Certification
- 2001 - Anatomic Pathology, American Board of Pathology
- 2001 - Clinical Pathology, American Board of Pathology
Professional Memberships
- Association of Pathology Chairs
- College of American Pathologists
- United States & Canadian Academy of Pathology
- American Society for Clinical Pathology
- Western New York Society of Surgical Pathologists
Honors & Awards
- 2021-2023 - Top Doctor, Buffalo Spree Magazine
- 2007-2012, 2013-2026 - University at Buffalo Outstanding ACGME Accreditation Award
- 2013-2014 - University at Buffalo Outstanding ACGME Accreditation Award
- 2012 - Outstanding Leadership Award, North American Journal of Medicine and Science
- 2010 - Dr. Edith E. Sproul Teaching Award for outstanding commitment and dedication to fellow education
- Leadership Development for Physicians in Academic Health Centers, Harvard School of Public Health, Boston Massachusetts (Eoin W. Trevelyan, D.B.A.)
- Executive Development RV Rhodes
- Pathology Leadership Academy by Association of Pathology Chairs
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.
Featured on CancerTalk
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Publications
- Kokai, Yasuo, Myers, Jeffrey N., Wada Takuro., Brown, Valerie I., LeVea, Charles M., Davis, James G., Dobashi, Kunio, and Greene, Mark I. Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts. Cell (1989) Jul 28; 58:287-292
- Qian, Xiaolan, LeVea, Charles M., Freeman, John K., Dougall, William C., and Greene, Mark I. Heterodimerization of epidermal growth factor receptor and wild type or kinase deficient neu: a mechanism of interreceptor kinase activation and transphosphorylation. Proceedings of the National Academy of Sciences of the United States of America (1994) Feb 15; 91(4):1500-1504
- Rajput A, Dominguez I, Rose R, Beko A, LeVea C, Sharratt E, Mazurchuk R, Brattain MG, Wang J. Characterization of HCT 116 Human Colon Cancer Cells in an Orthotopic Model. J Surg Res. (2008) Jun; 147(2):276-281
- Samanta, A., LeVea, Charles M., Dougall, William C., Qian, Xiaolan, and Greene, Mark I. Ligand and p185c-neu density govern receptor interactions and tyrosine kinase activation. Proceedings of the National Academy of Sciences of the United States of America (1994) Mar; 91(5):1711-1715
- Rashmi Pande, Annette Sunga, Charles LeVea, Gregory E. Wilding, Wiam Bshara, Mary Reid, and Marwan G. Fakih. Significance of signet-ring cells in patients with colorectal cancer. Dis Colon Rectum (2008) Jan; 51(1):50-55.