John Carethers
· MD, MACP, FAACRVerifiedUniversity of California, San Diego · Gastroenterology
Active 1987–2026
About
John M. Carethers is the Vice Chancellor for Health Sciences at the University of California San Diego, where he also holds the titles of Distinguished Professor of Medicine and Adjunct Professor of Public Health. He leads the School of Medicine, Skaggs School of Pharmacy and Pharmaceutical Sciences, Herbert Wertheim School of Public Health and Human Longevity Science, and UC San Diego Health. In this role, Dr. Carethers drives the overarching strategy for all of Health Sciences, working with campus and health system leadership to expand UC San Diego Health's clinical enterprise, foster research collaborations, enhance educational opportunities, and expand philanthropic participation. His leadership and collaborative approach continue to enhance the global prestige and distinction of the university's health sciences. A distinguished physician-scientist, Dr. Carethers specializes in gastroenterological research and treatment, with clinical and research interests including familial colon cancer syndromes, mechanisms of tumor progression, DNA mismatch repair, and colorectal cancer disparities. He joined UC San Diego in 2023 after a 13-year tenure at the University of Michigan, where he served as the C. Richard Boland Distinguished University Professor and the John G. Searle Professor and chair of the Department of Internal Medicine. Prior to that, he spent nearly 15 years at UC San Diego School of Medicine, including serving as chief of the Division of Gastroenterology, where he secured the inaugural NIH-funded Gastroenterology Center Grant to support scientific growth and partnerships with local institutions. Dr. Carethers earned his medical degree from Wayne State University School of Medicine in 1989, completed his residency at Massachusetts General Hospital in 1992, and his gastroenterology fellowship at the University of Michigan in 1995. He has served as president of both the Association of American Physicians and the American Gastroenterological Association, and has held leadership roles in the American Association for Cancer Research, including chairing the Minorities in Research Council and contributing to the AACR Cancer Health Disparities Reports. He is an elected member of the National Academy of Medicine.
Research topics
- Internal medicine
- Medicine
- Political Science
- Virology
- Sociology
- Environmental health
- Gerontology
- Oncology
- Pathology
- Demography
Selected publications
Early-Onset Colorectal Cancer in EMRO: GLOBOCAN 2022 Analysis and Projections
SSRN Electronic Journal · 2026-01-01
preprintOpen accessCancer Research · 2026-04-03
articleAbstract Background: Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST), microsatellite instability-high (MSI), and microsatellite stability (MSS) represent distinct forms of genomic instability and characterize colorectal cancer (CRC) genotypes related to DNA mismatch repair (MMR) deficiency and proficiency. EMAST is reported with a higher prevalence among African American (AA) vs White rectal cancers. The full clinical significance and phenotype of EMAST and its relationship with tumor characteristics, treatment factors, and patient outcomes remain unclear. Aim: We compared clinical characteristics, treatment patterns, and survival outcomes across EMAST, MSI, and MSS genotypes among AA CRC patients, and evaluated whether these genotypes have distinct prognostic or therapeutic associations. Methods: We retrospectively analyzed 304 CRC patients at Howard University, the majority being from AAs. Patients’ CRCs were assessed for EMAST, MSI, and MSS via fragment analysis. Clinical variables, including demographics, survival, tumor location, and treatment history, were compared across groups. Remission and recurrence outcomes were assessed. Statistical significance was determined using p-values provided in the dataset. Results: Patients with EMAST CRCs demonstrated higher overall[JC1] mortality when compared with patients with MSI and MSS CRCs (32% vs 18% vs 14%, respectively). The higher mortality between patients with MSI versus MSS CRCs may reflect a greater proportion of stage III tumors in the MSI vs MSS subgroup (n=14, 48.3% vs n=91, 39%) as advanced stage is strongly associated with poor survival. Patients with MSI CRCs demonstrated more right-sided tumors (46%) than patients with MSS (13%) or EMAST (15%) CRCs. Symptom-wise, gastrointestinal bleeding was the most frequent occurring in 25%, 19% and 12% of patients with MSS, EMAST, and MSI CRCs, respectively. Treatment-wise, chemotherapy was administered to 57%, 63% and 57% of patients with EMAST, MSI, and MSS CRCs, and 84%, 100%, 76%, respectively, were treated with radiotherapy. However, patient benefit was not equal based on the higher mortality of patients with EMAST CRCs. Demographic and clinical variables showed no significant differences (p>0.05) between patients with EMAST, MSS, and MSI CRCs. Similarly, we identified no differences among the 3 groups in overall survival or remission and recurrence rates (p>0.05). Conclusions: Patients with EMAST CRCs have the highest mortality despite similar treatment exposures and comparable demographic and clinical characteristics amongst our three groups. As expected, patients with MSI CRCs demonstrate a predominance of right-sided cancers. Overall, the EMAST genotype aligns with being a biological modifier that associates with poorer patient outcomes. Citation Format: Hassan Brim, Mudasir Rashid, Ahmed Imran, Somtochukwu Abazu, yumna siddiqui, Shweta Dixit, Anas Brim, Wardah Bajwa, Mrinalini Deverapal, Rumaisa Rashid, Aurmin Amirmokri, Chibuzor Nwachukwu, Neda Dezfuli, Rabia Zafar, Gholamreza Oskrochi, Zaki Sherif, Adeyinka O Laiyemo, John Carethers, Babak Shokrani, Hassan Ashktorab. Assessing prognostic and therapeutic associations across EMAST, MSI, and MSS among African Americans colorectal cancer subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4691.
Tu1315 A TARGETED GENETIC ALTERATION ASSOCIATED WITH ALCOHOL CONSUMPTION IN COLON CANCER
Gastroenterology · 2026-05-01
articleSenior authorGastrointestinal Endoscopy · 2026-05-01
articleGastrointestinal Endoscopy · 2026-05-01
articleJournal of Cancer · 2026-03-25
articleOpen accessSenior authorBackground: MutS Homolog 3 (MSH3), part of the MutS DNA mismatch repair complex with MSH2, can reversibly translocate from the nucleus to cytosol via IL-6 signaling, abrogating nuclear MutS function and is associated with metastasis and poor patient survival.A polymorphism consisting of deletion of 27-bp proximate to the nuclear localization signal (NLS) (27bpMSH3) allows MSH3 cytosolic retention with IL-6 or oxidative stress.Here, we examined for IL-6-induced post-translational modifications associated with MSH3 cytosolic translocation.Methods: We utilized MSH3-genotyped colon cancer cell lines after IL-6 treatment to assess post-translational modification of MSH3 via Western blots (WB).We modified sequences within the MSH3-NLS-EGFP reporter construct to assess MSH3 localization via immunofluorescent microscopy and WB after nuclear-cytosolic fractionation.Immunoprecipitation (IP) followed by WB was used to study post-IL-6-induced interactions with MSH3.Results: MSH3 and 27bpMSH3 increased serine phosphorylation after 2 hours followed by tyrosine phosphorylation 18 hours post IL-6 treatment, with 27bpMSH3 showing more robust phosphorylation than MSH3 likely due to increased cytosolic translocation.MSH3 cytosolic localization was enhanced by acetylation of lysine residues within MSH3's NLS, specifically at residues K 99 , K 100 and K 103 .With the observed acetylation control for MSH3 cytosolic localization, IP experiments demonstrate binding of cytosolic-located histone deacetylase 6 (HDAC6) to acetylated 27bpMSH3.Conclusions: Polymorphic MSH3 undergoes serine/tyrosine phosphorylation and NLS acetylation upon IL-6 signaling for its nuclear-cytosolic shift and binds HDAC6 in the cytosol which may contribute to anticipated deacetylation and MSH3 protein stability when separated from MSH2.These modifications might be targeted to regulate MSH3's intracellular localization.
Gastroenterology · 2026-05-01
articleJCI Insight · 2026-04-28
articleOpen accessPhysician-scientists represent one of the most impactful, yet underrecognized, innovations of 20th century academic medicine. Defined by a commitment to full-time careers in investigative work, physician-scientists have repeatedly demonstrated a unique ability to identify and solve problems of unmet medical need in a focused and intentional manner using their dual training in clinical medicine and the scientific method as both stethoscope and scalpel. Unfortunately, mounting financial pressures from both the clinical and research marketplaces have placed this storied workforce in jeopardy due to the absence of a dedicated and explicitly defined vocational structure and business model. This white paper reports the output of a consortium of academic medical centers, foundations and professional societies seeking to remedy this deficiency. This consortium specifically developed a framework to formalize the career path of physician-scientist faculty into a professionally unified and financially sustainable structure in a way that could be adopted to different U.S. academic medical centers and health systems. Key components of this framework included an administratively operational definition of physician-scientists, and three central and interconnected pillars (academic, financial, and organizational) that are rooted in this foundational definition. Herein, we detail core concepts and concrete recommendations.
Cancer Research · 2026-04-03
articleSenior authorAbstract Background. We previously reported on an individual from a fourth family worldwide with early-onset colorectal adenocarcinoma with germline compound heterozygous MSH3 variants (c.2436-1G>A / c.3265A>T). Tumor DNA from this individual demonstrated microsatellite instability-low (MSI-L) and elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) suggestive that both alleles were pathogenic. Additionally, tumor cells exhibited MSH3 in the cytoplasm, with some cells showing loss of MSH6 that might be suggestive of at least one MSH3-expressing allele having a dominant-negative effect on MSH2, which binds to both MSH3 and MSH6 for their stability. Here, we aimed to prove that both MSH3 variants are pathogenic as well as to assess effects on other mismatch repair proteins. Methods. Both MSH3 variants, c.2436-1G>A and c.3265A>T, were introduced individually into SW620 cells using CRISPR/Cas9. Presence of each variant was confirmed by Sanger sequencing. Western blotting (WB) and fragment analysis were performed on variant clones and compared with parental SW620 cells. Results. We successfully established MSH3 variant clones with homozygous c.2436-1G>A and clones with homozygous c.3265A>T. WB analysis revealed complete loss of MSH3 protein in cells containing homozygous c.2436-1G>A. However, variant MSH3 protein was detected in cells containing homozygous c.3265A>T, although the amount of protein was less than that of wild-type (WT) MSH3 expressed in parental SW620. These results suggest that the transcription rate of variant c.3265A>T may be reduced and/or variant-generated protein may be less stable than WT MSH3. Expression levels of MSH2, MSH6 and MLH1 in these 2 variant cell lines were similar to expression in parental SW620 cells. MSI-L/EMAST was detected in 18.8% (6/32) of subclones isolated from each variant indicating loss of MMR function, whereas no subclones (0/32) from SW620 showed MSI-L/EMAST. Conclusions. We established cell models of two germline MSH3 variants (c.2436-1G>A and c.3265A>T) which had been identified in an early-onset colorectal cancer patient. Cells with each variant exhibited MSI-L/EMAST indicating loss of MSH3 function, proving that these two germline variants are pathogenic. As we did not observe any change in cell MSH6 expression, further studies are in progress to generate cells that are compound heterozygous for these two variants and to further elucidate the pathological effects of the combinations of these variants. Citation Format: Yuki Aisu, Minoru Koi, John M. Carethers, . Evidence for pathogenicity of inherited biallelic MSH3 variants causing early-onset colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6282.
Gastroenterology · 2026-05-01
article
Recent grants
NIH · $1.1M · 2006
(PQ3) Immune Modulation of DNA Mismatch Repair in Colorectal Cancer
NIH · $1.8M · 2016–2021
NIH · $477k · 2000
NIH · $2.7M · 2014
NIH · $1.4M · 2017
Frequent coauthors
- 106 shared
Minoru Koi
University of California, San Diego
- 80 shared
Stephanie Tseng-Rogenski
University of Michigan–Ann Arbor
- 61 shared
Jan Tack
- 54 shared
Barbara Jung
University of Washington
- 50 shared
Temitope O. Keku
University of North Carolina at Chapel Hill
- 35 shared
C. Richard Boland
University of California, San Diego
- 35 shared
Heekyung Chung
- 31 shared
Moriya Iwaizumi
Hamamatsu University School of Medicine
Education
- 1989
M.D.
Wayne State University School of Medicine
B.S.
Wayne State University
- 1992
M.D., Internal Medicine
Massachusetts General Hospital
- 1995
M.D., Gastroenterology
University of Michigan
Awards & honors
- C. Richard Boland Distinguished University Professor
- John G. Searle Professor
- Inaugural National Institutes of Health-funded Gastroenterol…
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