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Clinical and Translational Epidemiology Unit

Our mission is to advance epidemiologic investigation for the translation of discoveries into effective clinical interventions in chronic disease.

The MGH Clinical and Translational Epidemiology Unit is a new research unit within the Department of Medicine. The mission of the CTEU is to advance epidemiologic investigation for the translation of discoveries into effective clinical interventions.  The CTEU will utilize, develop, and optimize cutting edge epidemiologic methods to discover and characterize determinants of human health, develop novel preventive and therapeutic interventions, and elucidate molecular biomarkers for the development of precision medicine strategies.  Approaches will include the analysis of traditional epidemiologic exposures, as well as novel genetic, biochemical, metabolomic, proteomic, and microbial biomarkers.

Principal Investigators
Ashwin Ananthakrishnan, MD, MPH
Manish Gala, MD
Hamed Khalili, MD, MPH
Kyle Staller, MD, MPH

Postdoctoral Fellows
Yin Cao
Dawn Chong
David Drew
Amit Joshi
Paul Lochhead
Mingyang Song

Doctoral Students
Raaj Mehta

Research Coordinators
Kathleen Stewart

Programmers
Elaine Coughlan-Gifford

Administrative Assistants
Mariane Leonard

 

1.  Epidemiology of colorectal adenoma and cancer. We are leading several studies in the prevention of colorectal adenoma and cancer using chemopreventative drugs and lifestyle interventions. We are also focused on genetic and biochemical markers that may be used to stratify risk of colorectal cancer for individuals, as well as predict responsiveness to various interventions. 

2.  Biomarker trial of aspirin in colorectal neoplasia.  We conducting ASPIRED, an NCI-funded, randomized, clinical trial of aspirin among patients with a history of colorectal adenoma in relation to several cancer-specific biomarkers.  The ultimate goal is to understand the mechanistic basis by which aspirin reduces the risk of colorectal cancer.

3.  Epidemiology of the oral and gut microbiome. We have completed several prospective collections of the oral and gut microbiome to examine key questions regarding the stability of the microbiome over time, dietary and lifestyle determinants of the microbiome, and the association of the microbiome in relation to risk of several chronic diseases, including colorectal and other cancers.  We collaborate closely with leading immunologists, computational biologists, microbiologists, and biostatisticians in this field.

4.  Genomic landscape of interval cancers.  We are using state-of-the art genome sequencing techniques to identify molecular markers of colorectal cancers which evade traditional endoscopic detection. 

5.  Genetic epidemiology of colorectal cancer.  We are members of a national consortium of epidemiological studies of colorectal cancer which have assembled to conduct a large scale genome wide association study of colorectal cancer.  The primary focus is to investigate the interaction between known environmental risk factors for colorectal cancer and genetic risk loci, as well as the interaction between germline genetic risk factors and colorectal cancers defined by molecular subtypes.

6.  Survival in colorectal cancer.  We co-lead, with the Fred Hutchinson Cancer Research Center, the International Survival Analysis in Colorectal Cancer Consortium, an international collaboration of investigators which is conducting studies in genetic and lifestyle factors associated with survival among patients with colorectal cancer.


7.  Epidemiology of gastrointestinal bleeding. We focus on lifestyle risk factors for gastrointestinal bleeding, including intake of medications such as aspirin and NSAIDs in relation to g genetic and biomarker risk factors.

8.  Epidemiology of inflammatory bowel disease. We are examining lifestyle and dietary factors and risk of incident Crohn’s disease and ulcerative colitis.  Based on this work, we will ultimately examine how these factors interact with known genetic risk loci for Crohn’s and ulcerative colitis.

9.  Epidemiology of diverticulitis. We are studying the association of diet and lifestyle with risk of incident diverticulitis as well as recurrent diverticulitis.  We are also examining the role of biochemical markers in relation to risk of incident and recurrent disease.

10. Molecular imaging of colorectal neoplasia. In collaboration with biotechnology firms, we are leading an NCI-sponsored clinical trial to translate novel near infrared activatable agents that selectively target tumor-specific cathepsin proteases. We are interested in using these agents with fluorescent imaging endoscopy to enhance the detection of gastrointestinal neoplasia.

Please contact us if you are interested in potential postdoctoral or faculty positions.

Workshop on Metagenomics

The Harvard University Center for AIDS Research, in collaboration with the Ragon Institute of MGH, MIT and Harvard, and the Clinical and Translational Epidemiology Unit at MGH, is sponsoring a week-long workshop focused exclusively on computational approaches to metagenomic analysis.

  1. Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167(6):562-72.
  2. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007;356(21):2131-42.
  3. Cho E, Willett WC, Colditz GA, Fuchs CS, Wu K, Chan AT, Zeisel SH, Giovannucci EL. Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst. 2007;99(16):1224-31. PMCID: PMC2441932.
  4. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Wu K, Fuchs CS. Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology. 2008;134(1):21-8. NIHMSID: NIHMS38884.
  5. Chan AT, Zauber AG, Hsu M, Breazna A, Hunter DJ, Rosenstein RB, Eagle CJ, Hawk ET, Bertagnolli MM. Cytochrome P450 2C9 Variants Influence Response to Celecoxib for Prevention of Colorectal Adenoma. Gastroenterology. 2009;136(7):2127-36. PMCID: PMC2693443.
  6. Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA. 2009;302(6):649-58. PMCID: PMC2848289.
  7. Chan AT,  Baba Y, Shima K, Nosho K, Chung DC, Hung KE, Mahmood U, Madden K, Poss K, Ranieri A, Shue D, Kucherlapati R, Fuchs CS, Ogino S.  Cathepsin B expression and survival in colon cancer: Implications for molecular detection of neoplasia.  Cancer Epidemiol Biomarkers Prev. 2010. 19 (11): 2777-85. PMCID: PMC2976771.
  8. Huang ES, Strate LL, Ho WH, Lee SS, Chan AT. A prospective study of aspirin use and the risk of gastrointestinal bleeding in men.  PLOS One. 2010 Dec 29; 5(12): e15721. PMCID: PMC3012090.
  9. Chan AT, Ogino S, Giovannucci EL, Fuchs CS. Inflammatory markers are associated with risk of colorectal cancer and chemopreventative response to anti-inflammatory drugs. Gastroenterology. 2011. 140(3): 799-808. PMCID: PMC3049858.
  10. Huang ES, Strate LL, Ho WH, Lee SS, Chan AT. Long-term use of aspirin and the risk of gastrointestinal bleeding.  Am J Med.  2011. 124(5): 426-33.  PMCID: PMC3086018.
  11. Strate LL, Liu YL, Huang ES, Giovannucci EL, Chan AT. Use of aspirin and nonsteroidal anti-inflammatory drugs increases risk of diverticulitis and diverticular bleeding.  Gastroenterology. 2011; 140: 1427-1433.  PMCID: PMC3081980.
  12. Chan AT, Sima CS, Zauber AG, Ridker PM, Hawk ET, Bertagnolli MM.  C-reactive protein and risk of colorectal adenoma according to celecoxib treatment.  Cancer Prev Res. 2011. 4(8): 1-9.  PMCID: PMC3151679.
  13. Khalili H, Huang ES, Ananthakrishnan AN, Higuchi L, Richter JM, Fuchs CS, Chan AT. Geographical variation and the risk of inflammatory bowel disease among U.S. women. Gut 2012 Jan 11.  PMCID: PMC3418414.
  14. Khalili H, Huang ES, Jacobson BC, Camargo CA, Feskanich D, Chan AT. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective study. BMJ 2012; 344: e372.  PMCID: PMC3269660.
  15. Ananthakrishan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS, Chan AT. Higher predicted vitamin D status is associated with reduced risk of Crohn’s disease. Gastroenterology 2012; 142(3): 482-9. PMCID: PMC3367959.
  16. Ananthakrishan AN, Higuchi LM, Huang ES, Khalili H, Richter JM, Fuchs CS, Chan AT. Aspirin, nonsteroidal anti-inflammatory drugs, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Internal Med 2012; 156 (5): 350-59. PMCID: PMC3369539.
  17. Khalili H, Higuchi L, Ananthakrishnan AN, Feskanich D, Richter JR, Fuchs CS, Chan AT. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut 2012 May 22. PMCID: PMC3465475.
  18. Khalili H, Huang ES, Ogino S, Fuchs CS, Chan AT. A prospective study of bisphosphonate use and risk of colorectal cancer.  J Clin Oncology. 2012 May 29.  PMCID: PMC3434982.
  19. Phipps AI, Newcomb PA*, Garcia-Albeniz X, Hutter CM, White E, Fuchs CS, Hazra A, Ogino S, Nan H, Ma J, Campbell PT, Figueiredo JC, Peters U, Chan AT. Association between colorectal cancer susceptibility loci and survival time following diagnosis with colorectal cancer.  Gastroenterology 2012 July. 143(1): 51-54.  PMCID: PMC3579620.
  20. Liao X,  Lochhead, P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M,  Imamura Y, Qian Z, Baba Y,   Shima K;, Meyerhardt JA, Giovannucci E, Fuchs CS; Chan AT* , Ogino S* (co-senior authors) . Aspirin use, PIK3CA mutation, and colorectal cancer survival. N Engl J Med 2012 Oct 25;367(17):1596-606.  PMCID: PMC3532946
  21. Khalili H, Higuchi LM, Ananthakrishnan AN, Manson JE, Feskanich D, Richter JM, Fuchs CS, Chan AT.  Hormone therapy increases risk of ulcerative colitis but not Crohn's disease.  Gastroenterology. 2012 Nov. 143(5); 33(32): 8026-33. PMCID:PMC3480540
  22. Forman JP, Scott JB, Ng K, Drake BF, Suarez EG, Hayden DL, Bennett GG, Chandler PD, Hollis BW, Emmons KM, Giovannucci EL, Fuchs CS, Chan AT. Effect of vitamin D supplementation in blacks.  Hypertension. 2013 Apr;61(4):779-85.   PMCID: PMC3775458.
  23. Nishihara R, Lochhead P, Kuchiba A, Jung S, Yamauchi M, Liao X, Imamura Y, Qian ZR, Morikawa T, Wang M, Spiegelman D, Cho E, Giovannucci E, Fuchs CS, Chan AT*, Ogino S* (co-senior authors).  Aspirin use and risk of colorectal cancer according to BRAF mutation status.  JAMA. 2013. 309(24): 2563-71.  PMCID: PMC3743040
  24. Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Korzenik JR, Fuchs CS, Willett WC, Richter JM, Chan AT.  A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis.  Gastroenterology. 2013 Aug 1.  PMCID: PMC3805714.
  25. Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Fuchs CS, Willett WC, Richter JM, Chan AT.  Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease.  Gut. 2013 Jul 4.  PMCID: PMC3915038.
  26. Hiraki LT, Qu C, Hutter CM, Baron J, Berndt SI, Bezieau S, Brenner H, Caan BJ, Casey G, Chang-Claude J, Chanock SJ, Conti DV, Duggan D, Fuchs CS, Gallinger S, Giovannucci EL, Harrison TA, Hayes RB, Hazra A, Henderson B, Hoffmeister M, Hopper JL, Hudson TJ, Jenkins MA, Küry S, Le Marchand L, Lemire M, Ma J, Manson JE, Nan H, Newcomb PA, Ng K, Potter JD, Schoen RE, Schumacher F, Seminara D, Slattery ML, Wactawski-Wende J, White E, Wu K, Zanke BW, Kraft P, Peters U, Chan AT.  Genetic predictors of circulating vitamin 25-Hydroxyvitamin D and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2013. PMCID: PMC3818310.
  27. Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, Inamura K, Kim SA, Kuchiba A, Yamauchi M, Imamura Y, Willett WC, Rosner BR, Fuchs CS, Giovannucci E, Ogino S, Chan AT.  Long-term colorectal-cancer incidence and mortality after lower endoscopy.  N Engl J Med 2013 Sept 19; 369(12):1095-105.  PMCID: PMC3840160. 
  28. Maguire LH, Song M, Strate LE, Giovannucci EL, Chan AT.  Higher serum levels of vitamin D are associated with reduced risk of diverticulitis.  Clin Gastro Hepatol 2013.  PMCID: PMC3840074.
  29. Khalili H, Ananthakrishnan AN, Konijeti GG, Liao X, Higuchi LM, Fuchs CS, Spiegelman D, Richter JM,  Korzenik JR, Chan AT.  Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses’ Health Study cohorts.  BMJ. 2013 Nov 14.  PMCID: PMC3935281.
  30. Nan H, Morikawa T, Suuriniemi M, Imamura Y, Werner L, Kuchiba A, Yamauchi M, Hunter DJ, Kraft P, Giovannucci EL, Fuchs CS, Ogino S, Freedman ML, Chan AT.  Aspirin use, 8q24 single nucleotide polymorphism rs6983267 and colorectal cancer according to CTNNB1 alterations.  J Natl Cancer Inst 2013 Dec 18; 105(24): 1852-61. PMCID: PMC3866156.
  31. Konijeti GG, Shrime MG, Ananthakrishnan AN, Chan AT. Cost-effectiveness analysis of chromoendoscopy for colorectal cancer surveillance in patients with ulcerative colitis.  Gastrointest Endosc. 2014 Mar; 79(3): 455-65. PMCID: PMC4116277.
  32. Boylan, MR, Khalili H, Huang ES, Michaud DS, Izard J, Joshipura KJ, Chan AT. A prospective study of periodontal disease and risk of gastric and duodenal ulcer in male health professionals. Clin Transl Gastroenterol. 2014;5:e49. PMCID: PMC3940834.
  33. Mehta RS, Bezawada N, Wu K, Garcia-Albeniz X, Morikawa T, Fuchs CS, Ogino S, Giovannucci E, Chan AT. A prospective study of macrophage inhibitory cytokine-1 and risk of colorectal cancer.  J Natl Cancer Inst. 2014 Feb 24. [Epub ahead of print].  PMID: 24565956. PMCID: PMC3982884.
  34. Fink S, Yamauchi, M, Nishihara R, Jung S, Kuchiba A, Wu K,  Cho E, Giovannucci E, Fuchs C, Ogino S, Markowitz SD,  Chan AT. Aspirin and the risk of colorectal cancer in relation to expression of 15-Hydroxyprostaglandin dehydrogenase expression.  Sci Transl Med 2014 Apr 23; 6(233). PMCID:PMC4030641.
  35. Bezawada N, Song M, Wu K, Mehta RS, Milne G, Fuchs CS, Giovannucci EL, Chan AT.  Urinary prostaglandin metabolites (PGE-M) are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.  Cancer Prev Res. 2014 May 13. PMCID: PMC4085181.
  36. Franzosa EA, Morgan XC, Segata N, Waldron L, Reyes J, Earl AM, Giannoukos G, Boylan MR, Ciulla D, Gevers D, Izard J, Garrett WS, Chan AT, Huttenhower C. Relating the metatranscriptome and metagenome of the human gut.  Proc Natl Acad Sci USA.  2014 May 19. PMCID: PMC4050606.
  37. King LY, Johnson KB, Zheng H, Wei L, Gudewicz T, Hoshida Y, Corey KE, Ajayi T, Ufere N, Baumert TF, Chan AT, Tanabe KK, Fuchs BC, Chung RT. Host genetics predict clinical deterioration in HCV-related cirrhosis. PLoS One. 2014 Dec 12;9(12):e114747. doi: 10.1371/journal.pone.0114747. eCollection 2014. PMCID: PMC4264769.
  38. Maguire LH, Song M, Strate LL, Giovannucci EL, Chan AT. Association of geographic and seasonal variation with diverticulitis admissions.  JAMA Surg. 2015 Jan; 150(1) 74-7. 
  39. Nan H, Hutter CM, Lin Y, Jacobs EJ, Ulrich CM, White E, Baron JA, Berndt SI, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chang-Claude J, Chanock SJ, Cotterchio M, Duggan D, Figueiredo JC, Fuchs CS, Giovannucci EL, Gong J, Haile RW, Harrison TA, Hayes RB, Hoffmeister M, Hopper JL, Hudson TJ, Jenkins MA, Jiao S, Lindor NM, Lemire M, Le Marchand L, Newcomb PA, Ogino S, Pflugeisen BM, Potter JD, Qu C, Rosse SA, Rudolph A, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Thibodeau SN, Thomas F, Thornquist M, Warnick GS, Zanke BW, Gauderman WJ, Peters U, Hsu L, Chan AT.  Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA. 2015 Mar 17.  PMCID: PMC4382867
  40. Song M, Nishihara R, Wu K, Qian ZR, Kim SA, Sukawa Y, Mima K, Inamura K, Masuda A, Yang J, Fuchs CS, Giovannucci EL, Ogino S, Chan AT. Marine n-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability. J Natl Cancer Inst. 2015 Mar 25; 107(4).  PMCID: PMC4402363.
  41. Gala MK, Austin T, Ogino S, Chan AT.  TFF2-CXCR4 Axis is associated with BRAF V600E colon cancer.  Cancer Prev Res.  2015 Apr 21.  PMCID: PMC4490961.

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