Download : Owyang, Chung BIOGRAPHICAL SKETCH

Program Director/Principal Investigator (Last, First, Middle):
Owyang, Chung
BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
JOHN M. CARETHERS, M.D.
John G. Searle Professor of Internal Medicine
Chair, Department of Internal Medicine
(effective 11/01/2009)
eRA COMMONS USER NAME (credential, e.g., agency login)
jcarethers
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
Wayne State University
B.S.
1985
Biological Sciences
Wayne State University
M.D.
1989
Medicine
Massachusetts General Hospital
Residency
1992
Internal Medicine
University of Michigan Hospitals
Fellowship
1995
Gastroenterology
A. Positions and Employment
1995-2001
Assistant Professor of Medicine in Residence, University of California, San Diego
2000-2004
Gastroenterology Fellowship Director, University of California, San Diego
2001-2005
Associate Professor of Medicine, University of California, San Diego
2002-2005
Chief, Gastroenterology Section, VA San Diego Healthcare System
2004-2009
Chief, Division of Gastroenterology, University of California, San Diego
2005-2009
Professor of Medicine (tenured), University of California, San Diego
2007-2010
Director, UCSD Gastroenterology NIH T32 Training Grant
2007-2009
Director, UCSD NIH Digestive Diseases Research Development Center (DDRDC)
2008-2009
co-Program Leader, Reducing Cancer Disparities, UCSD Comprehensive Cancer Center
11/2009John G. Searle Endowed Professor of Internal Medicine, University of Michigan
11/2009Chairman, Department of Internal Medicine, University of Michigan
Other Experience and Professional Memberships
2000-2003
Editorial Board, American Journal of Physiology: Gastrointestinal & Liver Physiology
2000-2003
Associate Editor, Encyclopedia of Gastroenterology, Elsevier Academic Press
2002-2006
NIH CSR Gastrointestinal Cell and Molecular Biology Study Section (GCMB)
2006-2011
Board of Editors, Gastroenterology; Section Editor, This Month in Gastroenterology
2006-2008
National Commission on Digestive Diseases (appointed by Elias Zerhouni, M.D.)
2007-2011
AGA Council; elected Vice-Chair (07-09) and Chair (09-11) of Gastrointestinal Oncology Section
2009-2010
AGA Underrepresented Minorities Committee
Honors
Alpha Omega Alpha Honor Medical Society (1988); Commonwealth Fund Medical Research Fellow, National
Medical Fellowships (1988); Henry J. Kaiser Family Foundation Award, National Medical Fellowships (1989);
Franklin C. McLean Award, National Medical Fellowships (1989); UCSD Department of Medicine Graduating
House Staff Teaching Award (1999); Fellow, American College of Physicians (FACP) (1999); Fellow, American
College of Gastroenterology (FACG) (2001); UCSD Gastroenterology Fellows Excellence in Clinical Teaching
Award (2004); Fellow, American Gastroenterological Association (AGAF) (2005); Western Association of
Physicians (2006); UCSD School of Medicine Vice-Chancellor’s Award for Mentoring Excellence (2006);
American Society for Clinical Investigation (2008)
B. Selected peer-reviewed publications (in chronological order)
1. Koi M, Umar A, Chauhan DP, Cherian SP, Carethers JM, Kunkel TA, Boland CR. Human chromosome 3
corrects mismatch repair deficiency and microsatellite instability and reduces N-methyl-N’-nitro-Nnitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation. Cancer Res
1994;54:4308-4312. PMID: 8044777
PHS 398/2590 (Rev. 11/07)
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Principal Investigator/Program Director (Last, First, Middle):
CARETHERS, John M.
2. Hawn MT, Umar A, Carethers JM, Marra G, Kunkel TA, Boland CR, Koi M. Evidence for a connection
between the mismatch repair system and the G2 cell cycle checkpoint. Cancer Res 1995;55:3721-3725.
3. Luce MC, Marra G, Chauhan DP, Laghi L, Carethers JM, Cherian SP, Hawn MT, Binnie CG, Kam-Morgan
LNW, Cayouette MC, Koi M, Boland CR. In vitro transcription/translation assay for the screening of hMLH1
and hMSH2 mutations in familial colon cancer. Gastroenterology 1995;109:1368-1374. PMID: 7557107
4. Carethers JM, Hawn MT, Chauhan DP, Luce MC, Marra G, Koi M, Boland CR. Competency in mismatch
repair prohibits clonal expansion of cancer cells treated with N-methyl-N’-nitro-N-nitrosoguanidine. J Clin
Invest 1996; 98:199-206. PMID: 8690794
5. Zigman AF, Lavine JE, Jones MC, Boland CR, Carethers JM. Localization of Bannayan-Riley-Ruvalcaba
syndrome gene to chromosome 10q23. Gastroenterology 1997; 113:1433-1437. PMID: 9352843
6. Carethers JM, Hawn MT, Greenson JK, Hitchcock CL, Boland CR. Prognostic significance of allelic loss at
chromosome 18q21 for stage II colorectal cancer. Gastroenterology 1998; 114:1188-1195. PMID: 9609755
7. Carethers JM, Furnari FB, Zigman AF, Lavine JE, Jones MC, Graham GE, Teebi AS, Huang H-JS, Ha HT,
Chauhan DP, Chang CL, Cavenee WK, Boland CR. Absence of PTEN/MMAC1 germline mutations in
sporadic Bannayan-Riley-Ruvalcaba syndrome. Cancer Res 1998; 58:2724-2726. PMID: 9661881
8. Carethers JM, Chauhan DP, Fink D, Nebel S, Bresalier RS, Howell SB, Boland CR. Mismatch repair
proficiency and in vitro response to 5-fluorouracil. Gastroenterology 1999; 117: 123-131. PMID: 1038191
9. Carethers JM. Racial and ethnic factors in the genetic pathogenesis of colorectal cancer. J Assoc Acad
Minor Phys 1999; 10:59-67. PMID: 10826011
10. Carethers JM, Pham T-TT. Mutations of transforming growth factor 1 type II receptor, BAX, and insulinlike growth factor II receptor genes in microsatellite unstable cell lines. In Vivo 2000; 14:13-20. PMID:
10757056
11. Yashiro M, Carethers JM, Laghi L, Saito K, Slezak P, Jaramillo E, Rubio C, et. al. Genetic pathways in the
evolution of morphologically distinct colorectal neoplasms. Cancer Res 2001; 60:2676-2683. PMID:
11289147
12. Huang SC, Lavine JE, Boland PS, Newbury RO, Kolodner R, Pham T-TT, Boland CR, Carethers JM.
Germline characterization of early-aged onset of hereditary non-polyposis colorectal cancer. J Pediatr
2001; 138:629-635. PMID: 11343035
13. Gervaz P, Efron J, Poza AA, Chun SW, Pham T-TT, Woodhouse S, Wexner SD, Carethers JM. Loss of
heterozygosity and HIV infection in patients with anal squamous-cell carcinoma. Dis Colon Rectum
2001;44:1503-8. PMID: 11598481
14. Gervaz P, Cerottini J-P, Bouzourene H, Benhattar J, Chaubert P, Secic M, Gillet M, Carethers JM.
Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with
T3N0 colorectal cancer. Surgery 2002; 131:190-197. PMID: 11854698
15. Chang CL, Marra G, Chauhan DP, Ha HT, Chang DK, Ricciardiello L, Carethers JM, et. al. Oxidative
stress inactivates the DNA mismatch repair system. Am J Physiol Cell Physiol 2002; 283:C148-C154.
PMID: 12055083
16. Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Wasserman L, Compton C, et. al. Characterization of
sporadic colon cancer by patterns of genomic instability. Cancer Res 2003; 63:1608-11614. PMID:
12670912
17. Ashkortab H, Smoot DT, Carethers JM, Rahmanian M, Kittles R, Vosganian G, Doura M, Nidhiry E, Naab
T, Momen B, Shakhani S, Giardiello FM, High incidence of microsatellite instability in colorectal cancer
from African Americans. Clinical Cancer Res 2003; 9:1112-1117. PMID: 12631615
18. Chang D, Goel A, Ricciardiello L, Lee DH, Chang CL, Carethers JM, Boland CR. Effect of H2O2 on cell
cycle and survival in DNA mismatch repair-deficient and -proficient cell lines. Cancer Letters,
2003;195:243-251. PMID: 12767533
19. Carethers JM, Smith EJ, Behling CA, Nguyen L, Tajima A, Doctolero RT, Cabrera BL, Goel A, Arnold CA,
Miyai K, Boland CR. Use of 5-fluorouracil and survival in patients with microsatellite unstable colorectal
cancer. Gastroenterology 2004; 126: 394-401. PMID: 14762775
20. Jung B, Doctolero RT, Tajima A, Nguyen AK, Keku T, Sandler RS, Carethers JM. Loss of activin receptor
type 2 protein expression in microsatellite unstable colorectal cancers. Gastroenterology 2004; 126:654659. PMID: 14988818
21. Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli M,
Boland CR. Frequent inactivation of PTEN by promoter hypermethylation and its association with
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Principal Investigator/Program Director (Last, First, Middle):
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microsatellite instability-high (MSI-H) in sporadic colorectal cancers. Cancer Res 2004; 64:3014-3021.
PMID: 15126336
22. Tajima A, Hess M, Cabrera BL, Kolodner R, Carethers JM. The mismatch repair complex hMutS
recognizes 5-fluoruracil-modified DNA as a mechanism for chemosensitivity. Gastroenterology 2004;
127:1678-1684. PMID: 15578504
23. Iwamoto M, Hoffenberg EJ, Carethers JM, Doctolero R, Tajima A, Sugano K, Franklin WA, Ahnen DJ.
Nuclear accumulation of -catenin occurs commonly in the epithelial cells of juvenile polyps. Pediatric Res
2005; 57:4-9. PMID: 15557107
24. Satia JA, Keku T, Galanko JA, Martin C, Doctolero RT, Tajima A, Sandler RS, Carethers JM. Diet,
lifestyle, and genomic instability in the North Carolina Colon Cancer Study. Cancer, Epidemiol, Biomarkers,
and Prevention 2005; 14:429-436. PMID: 15734969
25. Ashktorab H, Smoot DT, Farzanmehr H, Fidelia-Lambert M, Momen B, Hylind L, Iacosozio-Dononue C,
Carethers JM, Goel A, Boland CR, Giardiello FM. Clinicopathological features and MSI in colorectal
cancers from African Americans. International Journal of Cancer 2005; 116:914-919. PMID: 15856472
26. Eaton, AM, Sandler RS, Carethers JM, Millikan RC, Galanko J, Keku TO. MTHFR 677 and 1298
polymorphisms, folate intake and microsatellite instability in colon cancer. Cancer, Epidemiology,
Biomarkers, and Prevention 2005; 14:2023-2029. PMID: 16103455
27. Carethers JM. Should African Americans be screened for colorectal cancer earlier? Nature Clinical
Practice Gastroenterology and Hepatology 2005; 2:352-353. PMID: 16265401
28. Yashiro M, Laghi L, Saito K, Carethers JM, Slezak P, Rubio C, Hirakawa K, Boland CR. Serrated
adenomas have a pattern of genetic alterations that distinguishes them from other colorectal polyps.
Cancer Epidemiol Biomarkers Prev 2005, 14:2253-2256. PMID: 16172239
29. Carethers JM. Unwinding the heterogeneous nature of hamartomatous polyposis syndromes. JAMA 2005;
294:2498-2500. PMID: 16287964
30. Carethers JM. Prospective evaluation of fluorouracil chemotherapy based on the genetic make-up of
colorectal cancer. Gut 2006; 55: 759-761. PMID: 16698750
31. Jung B, Smith EJ, Doctolero RT, Gervaz P, Alonso JC, Miyai K, Keku T, Sandler RS, Carethers JM.
Influence of target gene mutation on survival, stage, and histology in sporadic microsatellite unstable colon
cancers. International Journal of Cancer 2006; 118:2509-2513. PMID: 16380996
32. Beck SE, Jung BH, Fiorino A, Gomez J, Del Rosario E, Cabrera BL, Huang SC, Chow JYC, and Carethers
JM. Bone morphogenetic protein signaling and growth suppression in colon cancer. Am J Physiology GI &
Liver Physiology 2006; 291:G135-G145. PMID: 16769811
33. Jo, W-S, Carethers JM. Chemotherapeutic implications in microsatellite unstable colorectal cancer.
Cancer Biomarkers 2006; 2:51-60. PMID: 17192059
34. Jung BH, Beck SE, Cabral J, Chau E, Cabrera BL, Fiorino A, Smith EJ, Bocanegra M, Carethers JM.
Activin type 2 receptor restoration in MSI-H colon cancer suppresses growth and enhances migration with
activin. Gastroenterology 2007; 132:633-644. PMID: 17258738
35. Kurland J, Beck SE, Solomon C, Doctolero RT, Brann O, Carethers JM, Huang SC. Cyclooxygenase 2
expression in polyps from a juvenile polyposis syndrome patient with mutant BMPR1A. J Ped
Gastroenterol Nutrition 2007; 44:318-325. PMID: 17325551
36. Beck SE, Jung B, Del Rosario E, Gomez J, Carethers JM. BMP-induced growth suppression in colon
cancer cells is mediated by p21/WAF1 stabilization and modulated by RAS/ERK. Cell Signal 2007;
19:1465-1472. PMID: 17317101
37. Beck SE, Carethers JM. BMP suppresses PTEN expression via RAS/ERK signaling. Cancer Biol & Ther,
6:1313-1317, 2007. PMID: 18059158
38. Chow JYC, Quach KT, Cabrera BL, Cabral JA, Beck SE, Carethers JM. RAS/ERK modulates TGFregulated PTEN expression in human pancreatic adenocarcinoma cells. Carcinogenesis; 28:2321-2327,
2007. PMID: 17638924
39. Shin SK, Nagasaka T, Jung BH, Matsubara N, Kim WH, Carethers JM, Boland CR, Goel A. Epigenetic
and genetic alterations in Netrin-1 receptors UNC5C and DCC in human colon cancer. Gastroenterology;
133:1849-1857, 2007. PMID: 18054557
40. Chow JYC, Dong H, Quach KT, Nguyen PNV, Chen K, Carethers JM. TGF mediates PTEN suppression
and cell motility through calcium-mediated PKC activation in pancreatic cancer cells. Am J Physiol
Gastrointest Liver Physiol, 294:G899-G905, 2008. PMID: 18239055
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Principal Investigator/Program Director (Last, First, Middle):
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41. Grady WM and Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis.
Gastroenterology 135:1079-1099,2008. PMID: 18773902
42. Chow JYC, Cabral JA, Chang J, Carethers JM. TGF-beta modulates PTEN expression independently of
SMAD signaling for growth proliferation in colon cancer cells. Cancer Biol & Ther 7:1694-1699, 2008.
PMID: 18769113
43. Chung H, Young DJ, Lopez C, Le T-AT, Lee JK, Ream-Robinson D, Huang SC, Carethers JM. Mutation
rates of TGFBR2 and ACVR2 coding microsatellites in human cells with defective DNA mismatch repair.
PLoS ONE 3:e3463, 2008. PMID: 18941508
44. Carethers JM. Intersection of TGF-beta and Wnt signaling pathways in colorectal cancer and metastasis.
Gastroenterology 137:33-36, 2009. PMID: 19482104
45. Chung H, Lopez CG, Young DJ, Ream-Robinson D, Cabrera BL, Carethers JM. Flanking sequence
specificity determines coding microsatellite heteroduplex and mutation rates with defective DNA mismatch
repair. Oncogene, 2009 (accepted). PMID: pending
C. Research Support ongoing or completed during the last three years
R01 DK067287 (Carethers)
07/1/05 to 06/30/10
NIH/NIDDK
Microsatellite Instability and the DNA Mismatch Repair System
Major goals: To determine the mutational rates of DNA microsatellites in various DNA mismatch repairdeficient backgrounds, and to examine DNA structural changes upon the mutation rates.
Role: PI
R24 DK080506 (Carethers)
04/10/08 to 02/28/13
NIH/NIDDK
UCSD Digestive Diseases Research Development Center (DDRDC)
Major goals: To provide the framework to facilitate research productivity, foster new research directions, and
encourage collaborations for participating members through the use of 3 basic science cores centered on a
theme continuum of digestive disease organ inflammation to repair to transformation.
Role: PI
U54 CA132379 (Carethers and Navarro)
09/01/08 to 08/31/13
NIH/NCI
Comprehensive SDSU/UCSD Cancer Center Partnership
Major goals: To enhance research, training, and education in cancer disparities between SDSU and UCSD.
Role: co-PI
Full Project, U54 CA132384 (Carethers and McGuire)
11/01/08 to 8/31/11
NIH/NCI
Genomic instability, race, and immune relationships in colorectal cancer
Major goals: To evaluate the role of genomic instability and immune cell infiltration within colorectal cancers in
determining survival between African Americans and Caucasians.
Role: co-PI
P30 CA023100 (Carson)
05/01/07 to 04/30/12
NIH/NCI
UCSD Moores Comprehensive Cancer Center
Major goals: This grant provides support for the infrastructure and shared resources of the University of
California, San Diego Moores Comprehensive Cancer Center.
Role: Member and co-Program Leader for Reducing Cancer Disparities Program
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