Richard James Cote

Richard James Cote is a pathologist, academic and author. He is the Edward Mallinckrodt Professor and Chair of the Department of Pathology and Immunology at Washington University in St. Louis School of Medicine, and the Pathologist-in-Chief at Barnes Jewish Hospital.

Cote's research focuses on the cellular and molecular pathways of tumor progression, metastasis, and therapy response, developing nanoscale technologies for cancer diagnostics, and leading clinical trials in breast, lung, and bladder cancer, resulting in multiple patents. He has published research articles and four books including Immunomicroscopy: A Diagnostic Tool for the Surgical Pathologist and Modern Surgical Pathology. His contributions to the field led him to be listed as a top American doctor by US News, Newsweek Health and Castle Connolly among others. Additionally, he is the recipient of the 2013 Distinguished Alumnus of the Year award from UCI's School of Physical Sciences, the 2015 Miami Chamber of Commerce Bio-Medical Healthcare Heroes Award, and the 2016 Society for Personalized Nano-Medicine Excellence in Service Award.

Cote is a Fellow of the Royal College of Pathologists, the American Board of Pathology, Royal Society of Medicine and the International Society for Urological Pathology, as well as a Senior Member of the National Academy of Inventors, and an elected member of the Association of American Physicians.

Education and early career
Cote earned a BA in Chemistry and a BS in Biology from the University of California, Irvine in 1976, followed by an MD from the University of Chicago in 1980. He completed a surgical internship at the University of Michigan (1980-1981), pursued a pathology residency at Cornell University (1985-1987), and held several fellowships at Memorial Sloan Kettering Cancer Center between 1981 and 1990, including a post-doctoral fellowship with Lloyd Old at MSKCC in tumor immunology. Concurrently, he served as a Research Associate at Memorial Sloan Kettering (1983-1985) and as a Clinical Instructor at Cornell University (1987-1990).

Career
Cote continued his academic career as an Assistant Professor in the Department of Pathology at the University of Southern California School of Medicine from 1990 to 1995. His appointment was later extended to the Department of Urology, when he became Associate Professor in 1995 and Professor in 1999. In 2009, he took on the role of Professor and Chair of the Department of Pathology at the Miller School of Medicine at the University of Miami, before joining the Department of Pathology and Immunology at Washington University School of Medicine, where he has held the position as the Edward Mallinckrodt Professor and Chair of the Department of Pathology and Immunology since 2019.

Cote assumed the role of an Associate Member at the University of Southern California Norris Comprehensive Cancer Center from 1991 to 1995, later becoming a Member until 2009. During this time, he also served as an Attending Pathologist and Director of the Laboratory of Immuno and Molecular Pathology. From 1997 to 2009, he directed the Genitourinary Cancer Program at Norris Cancer Center and led the USC Biomedical Nanoscience Initiative from 2005 to 2009. Subsequently, from 2009 to 2015, he directed the Genitourinary Cancer Program and chaired the Department of Pathology at the University of Miami Sylvester Comprehensive Cancer Center. He also served as Director of the Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute and held the Joseph R. Coulter Jr. Chair in the Department of Pathology until 2019, when he became Chair of the Department of Pathology and Immunology at the Washington University School of Medicine.

Cote has founded technology-based companies including Impath, Clarient, Filtini, Sensitini, and Circulogix. From 2009 to 2019, he served as Chief of Pathology at Jackson Memorial Hospital before transitioning to the role of Pathologist-in-Chief at Barnes-Jewish Hospital, where he also holds a position on the Board of Directors.

Research
Cote has contributed to the field of pathology by elucidating cellular and molecular pathways of tumor progression, metastasis, and therapy response. He has developed programs to explore metastatic cancer spread and circulating tumor cell (CTC) biology, and has led clinical trials in breast, lung, and bladder cancer, holding patents in cancer-related and nanoscale technologies.

Works
Cote has published books on cancer therapy and immunohistochemistry. He co-authored the second and third editions of the standard text Immunomicroscopy: A Diagnostic Tool for the Surgical Pathologist with Clive Roy Taylor, providing clinical coverage, along with methods and expert interpretation skills for diagnosing pathology through immunomicroscopic techniques. In a review for Mayo Clinic Proceedings, Peter M. Banks stated that it is an "outstanding book that serves both as a reference source for methodologic details and as a conceptual text for scientific principles and diagnostic applications." Later, he collaborated with Noel Weidner, Saul Suster and Lawrence Weiss for evaluating surgical specimens, integrating clinical, gross, microscopic, immunohistochemical, and molecular genetic features in two editions of Modern Surgical Pathology, which was called "a thorough and definitive 2-volume textbook" by Atiya Mansoor.

Cote co-edited two volumes in the "Current Cancer Research" book series: Circulating Tumor Cells: Advances in Basic Science and Clinical Applications with Ram Datar, and Advances in Liquid Biopsy Technologies with Evi Lianidou. About the first edition, academic Sudeep Gupta remarked, "This book is a contemporary and comprehensive collection of reviews on technologies for estimating CTC, their genomic and functional characterization and clinical applications."

Cancer diagnosis and liquid biopsy
Cote has studied cancer detection and diagnosis throughout his career. In collaborative research, he developed guidelines to improve HER2 testing accuracy in invasive breast cancer, recommending standardized procedures and criteria to ensure reliable results for all cases. He is one of the founders of the field of liquid biopsy for cancer detection and evaluation and published the first study on the US on disseminated tumor cells (DTC) focusing on patients with early stage breast cancer, and followed this up with a study showing that such cells identify patients at increased risk for metastasis. He later worked with Munro Neville and the Ludwig Institute to publish a study showing that identification of occult tumor cells in the lymph nodes of patients with early-stage breast cancer identify those with increased risk for metastasis. His work also revealed breast cancer stem cell phenotype in bone marrow disseminated tumor cells of early breast cancer patients, suggesting implications for metastasis and underscoring the need for further molecular analysis. Additionally, he introduced a parylene membrane microfilter device for quick and efficient capture and analysis of circulating tumor cells (CTCs) in human blood.

In a paper published in the New England Journal of Medicine, Cote and colleagues identified nuclear p53 accumulation as an independent predictor of poor outcomes in bladder-confined transitional-cell carcinoma, while also demonstrating genetic discrepancies between papillary and flat transitional cell carcinomas, indicating diverse pathways of tumor progression. He further showed that microcantilevers can detect prostate-specific antigen (PSA) in various concentrations, suggesting their potential for diagnosing prostate cancer and other diseases. Later, alongside Shan-Rong Shi and Clive Taylor, he reviewed the antigen retrieval technique in immunohistochemical staining, emphasizing the need for standardized protocols and optimal retrieval methods.

Cancer therapy
Cote's work on cancer therapy has focused on improving cancer treatment methods. He evaluated long-term outcomes of radical cystectomy and pelvic lymph node dissection in invasive bladder cancer, revealing that tumor stage and lymph node status significantly impact recurrence-free survival, supporting aggressive surgical management for excellent long-term results. In another joint research effort, he showed that adjuvant cisplatin-based chemotherapy after radical cystectomy improves survival in muscle-invasive bladder cancer patients. In 2022, he conducted a similar study which found that cisplatin-based adjuvant chemotherapy significantly improves overall, locoregional recurrence-free, and metastasis-free survival in patients with muscle-invasive bladder cancer.

Digital pathology and artificial intelligence
Cote was a Principal Consultant to Chromavision, one of the first companies to use digital pathology in diagnostic applications, where he led the effort to use digital images to detect CTC and to quantify Her2 expression in breast cancer. In addition, he has worked with colleagues at Caltech to develop microscopic methods that are designed to produce all-in-focus digital images of histologic and cytologic preparations, important for AI applications. He has gone on to describe the use of digital microscopy and AI to identify CTC. Most recently, his team described the application of AI on the diagnostic histology of patients with early stage lung cancer to predict which patients will suffer metastasis.

Awards and honors

 * 2010 – Elected Member, Association of American Physicians
 * 2013 – Distinguished Alumnus of the Year, University of California, Irvine
 * 2015 – Bio-Medical Healthcare Heroes Award, Miami Chamber of Commerce
 * 2016 – Excellence in Service Award, Society for Personalized Nano-Medicine>
 * 2021 – Senior Member, National Academy of Inventors
 * 2024 – Fellow, Royal Society of Medicine

Books

 * Immunomicroscopy: A Diagnostic Tool for the Surgical Pathologist (1994) ISBN 978-0721664620
 * Modern Surgical Pathology (2003) ISBN 978-0721672533
 * Circulating Tumor Cells, Advances in Basic Science and Clinical Applications (2016) ISBN 978-1493933617
 * Circulating Tumor Cells, Advances in Liquid Biopsy Technologies (2023) ISBN 978-3031229022

Selected articles

 * Esrig, D., Elmajian, D., Groshen, S., Freeman, J. A., Stein, J. P., Chen, S. C., ... & Cote, R. J. (1994). Accumulation of nuclear p53 and tumor progression in bladder cancer. New England Journal of Medicine, 331(19), 1259-1264.
 * Stein, J. P., Lieskovsky, G., Cote, R., Groshen, S., Feng, A. C., Boyd, S., ... & Skinner, D. G. (2001). Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. Journal of clinical oncology, 19(3), 666-675.
 * Wu, G., Datar, R. H., Hansen, K. M., Thundat, T., Cote, R. J., & Majumdar, A. (2001). Bioassay of prostate-specific antigen (PSA) using microcantilevers. Nature biotechnology, 19(9), 856-860.
 * Wolff, A. C., Hammond, M. E. H., Schwartz, J. N., Hagerty, K. L., Allred, D. C., Cote, R. J., ... & Hayes, D. F. (2006). American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Journal of clinical oncology, 25(1), 118-145.
 * Vizcaíno, J. A., Côté, R. G., Csordas, A., Dianes, J. A., Fabregat, A., Foster, J. M., ... & Hermjakob, H. (2012). The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013. Nucleic acids research, 41(D1), D1063-D1069.
 * Zhou, H., Watson, M., Bernadt, C. T., Lin, S., Lin, C. Y., Ritter, J. H., ... & Cote, R. J. (2024). AI‐guided histopathology predicts brain metastasis in lung cancer patients. The Journal of Pathology, 263(1), 89-98.\