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    Carlo Maley, PhD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentSurgery
    Address2340 Sutter Street
    San Francisco CA 94143
    Phone415-476-9239

       Overview 
       Overview
      I specialize in the evolutionary analysis of neoplasms, both for understanding progression to malignancy and the response to therapy. Most of my work has been in Barrett’s Esophagus and acute myeloid leukemia (AML), though I am interested in all cancers. We have shown that measures of intra-tumor genetic heterogeneity predict progression to malignancy in Barrett’s esophagus. We predict that the degree of heterogeneity should also correlate with the presence of a resistant clone, and so predict time until relapse after therapy. We are developing phylogenetic methods to measure the dynamics in tumors including mutation rates, clonal expansions, stem cell population sizes and time since initiation. We are interested in whole genome sequencing and epigenetic profiling of pre-malignant and malignant neoplasms, particularly in cases where they can be tracked over time. We are currently usinging the techniques to study the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on clonal evolution in Barrett’s Esophagus.


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       Bibliographic 
       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Alcock J, Maley CC, Aktipis CA. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. Bioessays. 2014 Oct; 36(10):940-9.
        View in: PubMed
      2. Li X, Galipeau PC, Paulson TG, Sanchez CA, Arnaudo J, Liu K, Sather CL, Kostadinov RL, Odze RD, Kuhner MK, Maley CC, Self SG, Vaughan TL, Blount PL, Reid BJ. Temporal and Spatial Evolution of Somatic Chromosomal Alterations: A Case-Cohort Study of Barrett's Esophagus. Cancer Prev Res (Phila). 2014 Jan; 7(1):114-27.
        View in: PubMed
      3. Aktipis CA, Boddy AM, Gatenby RA, Brown JS, Maley CC. Life history trade-offs in cancer evolution. Nat Rev Cancer. 2013 Dec; 13(12):883-92.
        View in: PubMed
      4. Kostadinov RL, Kuhner MK, Li X, Sanchez CA, Galipeau PC, Paulson TG, Sather CL, Srivastava A, Odze RD, Blount PL, Vaughan TL, Reid BJ, Maley CC. NSAIDs modulate clonal evolution in Barrett's esophagus. PLoS Genet. 2013 Jun; 9(6):e1003553.
        View in: PubMed
      5. S Datta R, Gutteridge A, Swanton C, Maley CC, Graham TA. Modelling the evolution of genetic instability during tumour progression. Evol Appl. 2013 Jan; 6(1):20-33.
        View in: PubMed
      6. Sprouffske K, Athena Aktipis C, Radich JP, Carroll M, Nedelcu AM, Maley CC. An evolutionary explanation for the presence of cancer nonstem cells in neoplasms. Evol Appl. 2013 Jan; 6(1):92-101.
        View in: PubMed
      7. Sprouffske K, Merlo LM, Gerrish PJ, Maley CC, Sniegowski PD. Cancer in light of experimental evolution. Curr Biol. 2012 Sep 11; 22(17):R762-71.
        View in: PubMed
      8. Roche B, Hochberg ME, Caulin AF, Maley CC, Gatenby RA, Misse D, Thomas F. Natural resistance to cancers: a Darwinian hypothesis to explain Peto's paradox. BMC Cancer. 2012; 12:387.
        View in: PubMed
      9. Kosoff RE, Gardiner KL, Merlo LM, Pavlov K, Rustgi AK, Maley CC. Development and characterization of an organotypic model of Barrett's esophagus. J Cell Physiol. 2012 Jun; 227(6):2654-9.
        View in: PubMed
      10. Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012 Jan 19; 481(7381):306-13.
        View in: PubMed
      11. Aktipis CA, Kwan VS, Johnson KA, Neuberg SL, Maley CC. Overlooking evolution: a systematic analysis of cancer relapse and therapeutic resistance research. PLoS One. 2011; 6(11):e26100.
        View in: PubMed
      12. Merlo LM, Kosoff RE, Gardiner KL, Maley CC. An in vitro co-culture model of esophageal cells identifies ascorbic acid as a modulator of cell competition. BMC Cancer. 2011; 11:461.
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      13. Aktipis CA, Maley CC, Pepper JW. Dispersal evolution in neoplasms: the role of disregulated metabolism in the evolution of cell motility. Cancer Prev Res (Phila). 2012 Feb; 5(2):266-75.
        View in: PubMed
      14. Chen J, Sprouffske K, Huang Q, Maley CC. Solving the puzzle of metastasis: the evolution of cell migration in neoplasms. PLoS One. 2011; 6(4):e17933.
        View in: PubMed
      15. Reid BJ, Kostadinov R, Maley CC. New strategies in Barrett's esophagus: integrating clonal evolutionary theory with clinical management. Clin Cancer Res. 2011 Jun 1; 17(11):3512-9.
        View in: PubMed
      16. Sprouffske K, Pepper JW, Maley CC. Accurate reconstruction of the temporal order of mutations in neoplastic progression. Cancer Prev Res (Phila). 2011 Jul; 4(7):1135-44.
        View in: PubMed
      17. Caulin AF, Maley CC. Peto's Paradox: evolution's prescription for cancer prevention. Trends Ecol Evol. 2011 Apr; 26(4):175-82.
        View in: PubMed
      18. Merlo LM, Shah NA, Li X, Blount PL, Vaughan TL, Reid BJ, Maley CC. A comprehensive survey of clonal diversity measures in Barrett's esophagus as biomarkers of progression to esophageal adenocarcinoma. Cancer Prev Res (Phila). 2010 Nov; 3(11):1388-97.
        View in: PubMed
      19. Lai LA, Kostadinov R, Barrett MT, Peiffer DA, Pokholok D, Odze R, Sanchez CA, Maley CC, Reid BJ, Gunderson KL, Rabinovitch PS. Deletion at fragile sites is a common and early event in Barrett's esophagus. Mol Cancer Res. 2010 Aug; 8(8):1084-94.
        View in: PubMed
      20. Odze RD, Maley CC. Neoplasia without dysplasia: lessons from Barrett esophagus and other tubal gut neoplasms. Arch Pathol Lab Med. 2010 Jun; 134(6):896-906.
        View in: PubMed
      21. Pavlov K, Maley CC. New models of neoplastic progression in Barrett's oesophagus. Biochem Soc Trans. 2010 Apr; 38(2):331-6.
        View in: PubMed
      22. Cairo MS, Jordan CT, Maley CC, Chao C, Melnick A, Armstrong SA, Shlomchik W, Molldrem J, Ferrone S, Mackall C, Zitvogel L, Bishop MR, Giralt SA, June CH. NCI first International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the biological considerations of hematological relapse following allogeneic stem cell transplantation unrelated to graft-versus-tumor effects: state of the science. Biol Blood Marrow Transplant. 2010 Jun; 16(6):709-28.
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      23. Merlo LM, Maley CC. The role of genetic diversity in cancer. J Clin Invest. 2010 Feb; 120(2):401-3.
        View in: PubMed
      24. Merlo LM, Wang LS, Pepper JW, Rabinovitch PS, Maley CC. Polyploidy, aneuploidy and the evolution of cancer. Adv Exp Med Biol. 2010; 676:1-13.
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      25. Paulson TG, Maley CC, Li X, Li H, Sanchez CA, Chao DL, Odze RD, Vaughan TL, Blount PL, Reid BJ. Chromosomal instability and copy number alterations in Barrett's esophagus and esophageal adenocarcinoma. Clin Cancer Res. 2009 May 15; 15(10):3305-14.
        View in: PubMed
      26. Li X, Galipeau PC, Sanchez CA, Blount PL, Maley CC, Arnaudo J, Peiffer DA, Pokholok D, Gunderson KL, Reid BJ. Single nucleotide polymorphism-based genome-wide chromosome copy change, loss of heterozygosity, and aneuploidy in Barrett's esophagus neoplastic progression. Cancer Prev Res (Phila). 2008 Nov; 1(6):413-23.
        View in: PubMed
      27. Liu Z, Venkatesh SS, Maley CC. Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples. BMC Genomics. 2008; 9:509.
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      28. Chao DL, Eck JT, Brash DE, Maley CC, Luebeck EG. Preneoplastic lesion growth driven by the death of adjacent normal stem cells. Proc Natl Acad Sci U S A. 2008 Sep 30; 105(39):15034-9.
        View in: PubMed
      29. Pepper JW, Sprouffske K, Maley CC. Animal cell differentiation patterns suppress somatic evolution. PLoS Comput Biol. 2007 Dec; 3(12):e250.
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      30. Maley CC. Open questions in oesophageal adenocarcinogenesis. Gut. 2007 Jul; 56(7):897-8.
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      31. Lai LA, Paulson TG, Li X, Sanchez CA, Maley C, Odze RD, Reid BJ, Rabinovitch PS. Increasing genomic instability during premalignant neoplastic progression revealed through high resolution array-CGH. Genes Chromosomes Cancer. 2007 Jun; 46(6):532-42.
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      32. Srivastava A, Hornick JL, Li X, Blount PL, Sanchez CA, Cowan DS, Ayub K, Maley CC, Reid BJ, Odze RD. Extent of low-grade dysplasia is a risk factor for the development of esophageal adenocarcinoma in Barrett's esophagus. Am J Gastroenterol. 2007 Mar; 102(3):483-93; quiz 694.
        View in: PubMed
      33. Galipeau PC, Li X, Blount PL, Maley CC, Sanchez CA, Odze RD, Ayub K, Rabinovitch PS, Vaughan TL, Reid BJ. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med. 2007 Feb; 4(2):e67.
        View in: PubMed
      34. Kelloff GJ, Sullivan DC, Baker H, Clarke LP, Nordstrom R, Tatum JL, Dorfman GS, Jacobs P, Berg CD, Pomper MG, Birrer MJ, Tempero M, Higley HR, Petty BG, Sigman CC, Maley C, Sharma P, Wax A, Ginsberg GG, Dannenberg AJ, Hawk ET, Messing EM, Grossman HB, Harisinghani M, Bigio IJ, Griebel D, Henson DE, Fabian CJ, Ferrara K, Fantini S, Schnall MD, Zujewski JA, Hayes W, Klein EA, DeMarzo A, Ocak I, Ketterling JA, Tempany C, Shtern F, Parnes HL, Gomez J, Srivastava S, Szabo E, Lam S, Seibel EJ, Massion P, McLennan G, Cleary K, Suh R, Burt RW, Pfeiffer RM, Hoffman JM, Roy HK, Wang T, Limburg PJ, El-Deiry WS, Papadimitrakopoulou V, Hittelman WN, MacAulay C, Veltri RW, Solomon D, Jeronimo J, Richards-Kortum R, Johnson KA, Viner JL, Stratton SP, Rajadhyaksha M, Dhawan A. Workshop on imaging science development for cancer prevention and preemption. Cancer Biomark. 2007; 3(1):1-33.
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      35. Merlo LM, Pepper JW, Reid BJ, Maley CC. Cancer as an evolutionary and ecological process. Nat Rev Cancer. 2006 Dec; 6(12):924-35.
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      36. Chao DL, Maley CC, Wu X, Farrow DC, Galipeau PC, Sanchez CA, Paulson TG, Rabinovitch PS, Reid BJ, Spitz MR, Vaughan TL. Mutagen sensitivity and neoplastic progression in patients with Barrett's esophagus: a prospective analysis. Cancer Epidemiol Biomarkers Prev. 2006 Oct; 15(10):1935-40.
        View in: PubMed
      37. Kelloff GJ, Lippman SM, Dannenberg AJ, Sigman CC, Pearce HL, Reid BJ, Szabo E, Jordan VC, Spitz MR, Mills GB, Papadimitrakopoulou VA, Lotan R, Aggarwal BB, Bresalier RS, Kim J, Arun B, Lu KH, Thomas ME, Rhodes HE, Brewer MA, Follen M, Shin DM, Parnes HL, Siegfried JM, Evans AA, Blot WJ, Chow WH, Blount PL, Maley CC, Wang KK, Lam S, Lee JJ, Dubinett SM, Engstrom PF, Meyskens FL, O'Shaughnessy J, Hawk ET, Levin B, Nelson WG, Hong WK. Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward. Clin Cancer Res. 2006 Jun 15; 12(12):3661-97.
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      38. Maley CC. Multistage carcinogenesis in Barrett's esophagus. Cancer Lett. 2007 Jan 8; 245(1-2):22-32.
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      39. Maley CC, Rustgi AK. Barrett's esophagus and its progression to adenocarcinoma. J Natl Compr Canc Netw. 2006 Apr; 4(4):367-74.
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      40. Maley CC, Galipeau PC, Finley JC, Wongsurawat VJ, Li X, Sanchez CA, Paulson TG, Blount PL, Risques RA, Rabinovitch PS, Reid BJ. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet. 2006 Apr; 38(4):468-73.
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      41. Wongsurawat VJ, Finley JC, Galipeau PC, Sanchez CA, Maley CC, Li X, Blount PL, Odze RD, Rabinovitch PS, Reid BJ. Genetic mechanisms of TP53 loss of heterozygosity in Barrett's esophagus: implications for biomarker validation. Cancer Epidemiol Biomarkers Prev. 2006 Mar; 15(3):509-16.
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      42. Maley CC, Reid BJ. Natural selection in neoplastic progression of Barrett's esophagus. Semin Cancer Biol. 2005 Dec; 15(6):474-83.
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      43. Hornick JL, Blount PL, Sanchez CA, Cowan DS, Ayub K, Maley CC, Reid BJ, Odze RD. Biologic properties of columnar epithelium underneath reepithelialized squamous mucosa in Barrett's esophagus. Am J Surg Pathol. 2005 Mar; 29(3):372-80.
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      44. Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Blount PL, Reid BJ. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res. 2004 Oct 15; 64(20):7629-33.
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      45. Maley CC, Reid BJ, Forrest S. Cancer prevention strategies that address the evolutionary dynamics of neoplastic cells: simulating benign cell boosters and selection for chemosensitivity. Cancer Epidemiol Biomarkers Prev. 2004 Aug; 13(8):1375-84.
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      46. Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Reid BJ. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett's esophagus. Cancer Res. 2004 May 15; 64(10):3414-27.
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      47. Maley CC, Tapscott SJ. Selective instability: maternal effort and the evolution of gene activation and deactivation rates. Artif Life. 2003; 9(3):317-26.
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      48. Maley CC, Forrest S. Exploring the relationship between neutral and selective mutations in cancer. Artif Life. 2000; 6(4):325-45.
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      49. Maley CC. DNA computation: theory, practice, and prospects. Evol Comput. 1998; 6(3):201-29.
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      50. Maley C. Mutation rates as adaptations. J Theor Biol. 1997 Jun 7; 186(3):339-48.
        View in: PubMed
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