John Carethers, M.D.

John G. Searle Professor and Chair, Dept. of Internal Medicine

Biography

Dr. Carethers is a trained gastroenterologist and physician-scientist who focuses his research in the area of hereditary colon cancer genetics. Dr. Carethers received his B.S. degree in Biological Sciences with a minor in Chemistry from Wayne State University, and his M.D. with high distinction from the same institution. Dr. Carethers did his internship and residency in Internal Medicine at Massachusetts General Hospital, followed by a fellowship in gastroenterology at the University of Michigan. He was then recruited to the University of California San Diego where he grew his laboratory-based research in the area of DNA mismatch repair and colorectal cancer pathogenesis. He served in leadership roles including the gastroenterology fellowship director, the gastroenterology Section Chief for the VA San Diego Health System, then Division Chief for UC San Diego before being recruited to Michigan in November 2009 as Professor and Chair. He was the founding Director of the NIH-funded UCSD Gastroenterology Center grant, and was the director of the gastroenterology T32 training grant. His laboratory research continues to be funded by the NIH. He is a Senior Associate Editor for Gastroenterology, the highest impact gastroenterology journal (2011-2016). He was elected a member of the American Society for Clinical Investigation, and elected a member of the American Association of Physicians (AAP), and serves on the AAP Council. He was elected a member of the National Academy of Medicine (formerly the Institute of Medicine) in 2012.

Research Interests

Dr. Carethers’ laboratory studies the development and progression of colorectal neoplasms, using bench to bedside approaches in his translational laboratory. The laboratory focuses on familial and sporadic colorectal cancer, in particular, the consequences of defective DNA mismatch repair (MMR). Recently, the lab has focused on the role of one of the MMR proteins, hMSH3, and its biomarker EMAST. We are examining how MMR drives frameshift mutation rates of DNA sequences and how it contributes to copy number variation, how MMR executes cytotoxicity after 5-fluorouracil chemotherapy, and how inflammation and oxidative stress influences MMR function, and ultimately patient outcome.

Publications

Basa RCB, Davies V, Li X, Murali B, Shah J, Yang B, Li S, Khan MW, Tian M, Tejada R, Hassan A, Washington A, Mukherjee B, Carethers JM*, McGuire KL*. Decreased anti-tumor cytotoxic immunity among colon cancers from African Americans. (*co-senior authors) PLoS One. 2016 Jun 16;11(6):e0156660.

Munakata K, Uemura M, Tanaka S, Kawai K, Kano Y, Nishikawa S, Fukusumi T, Takahashi Y, Hata T, Nishimura J, Takemasa I, Mizushima T, Ikenaga M, Kato T, Murat K, Carethers JM, Yamamoto H, Doki Y, Mori M. Cancer stem-like properties in colorectal cancer cells with low proteasome activity. Clin Cancer Res 2016 (in press)

Suzuki S, Iwaizumi M, Tseng-Rogenski S, Hamaya Y, Miyajima H, Kanaoka S, Sugimoto K, Carethers JM. Production of truncated MBD4 protein by frameshift mutation in DNA mismatch repair-deficient cells enhances 5-fluorouracil sensitivity that is independent of hMLH1 status. Cancer Biol Ther. 2016 Apr 26:1-9.

Tang B, Chow JY, Dong TX, Yang S-M, Lu D-S, Carethers JM*, Dong H*. Calcium sensing receptor suppresses human pancreatic tumorigenesis through a novel NCX1/Ca2+/β-catenin signaling pathway. (*co-corresponding and senior authors) Cancer Lett 377:44-54, 2016.

Ashktorab H, Ahuja S, Kannan L, Llor X, Ellis N, Xicola RM, Adeyinka LO, Carethers JM, Brim H, Nouraie M. A meta-analysis of MSI frequency and race in colorectal cancer. Oncotarget. 2016 Apr 23;7(23):34546-57.

Koi M, Garcia M, Choi C, Kim H-R, Koike J, Hemmi H, Nagasaka T, Okugawa Y, Toiyama Y, Kitajima T, Chen Y-H, Mukherjee B, Boland CR, Carethers JM. Microsatellite alterations with allelic loss on 9p24.2 signify less aggressive colorectal cancer metastasis. Gastroenterology 150:944-955, 2016.

Hamaya Y, Guarinos C, Tseng-Rogenski SS, Iwaizumi M, Das R, Jover R, Castells A, Llor X, Andreu M, Carethers JM. Efficacy of 5-fluorouracil adjuvant therapy for patients with EMAST-positive stage II/III colorectal cancers. PLoS One 10(5):e0127591, 2015.

Carethers JM, Koi M, Tseng-Rogenski S. EMAST is a form of microsatellite instability that is initiated by inflammation and modulates colorectal cancer progression. Genes 6:185-205, 2015.

Tseng-Rogenski S, Hamaya Y, Choi D, Carethers JM. Interleukin 6 alters localization of hMSH3, leading to DNA mismatch repair defects in colorectal cancer cells. Gastroenterology 148:579-589, 2015.

Carethers JM. Screening for colorectal cancer in African Americans: Determinants and rationale for an earlier age to commence screening. Dig Dis Sci 60:711-21, 2015.

Fearon ER, Carethers JM. Molecular subtyping of colorectal cancer – time to explore both intertumoral and intratumoral heterogeneity to evaluate patient outcome. Gastroenterology 148:10-13, 2015.

Carethers JM, Murali B, Yang B, Doctolero RT, Tajima A, Basa R, Smith EJ, Lee M, Janke R, Ngo T, Tejeda R, Ji M, Kinseth M, Cabrera BL, Miyai K, Keku TO, Martin CF, Galanko JA, Sandler RS, McGuire KL. Influence of race on microsatellite instability and CD8+ T cell infiltration in colon cancer. PLoS One 9(6):e100461, 2014.

 

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