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Marcos R. Estecio, Ph.D.

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Assistant Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

The main focus of my research is to understand the origin and significance of abnormal epigenetic marking in cancer, with a special interest in DNA methylation.  My hypothesis is that genetic lesions are the underlying cause of the observed increase in DNA methylation in several tumors types. My working model is that the molecular signals dictated by these lesions do not affect the genome in a homogeneous fashion; a predisposing state must exist and in such rests the tissue specificity of genetic lesions and targeted DNA methylated genes. I am currently developing two main research projects based on the hypothesis stated above. In the first project, using colorectal tumors as a model, I am investigating the presence of genetic lesions that are correlated with a form of epigenetic instability termed CIMP (CpG Island Methylator Phenotype). In a second project, I am taking a comprehensive approach to link gene regulatory signals (including chromatin organization) to aberrant DNA methylation. I anticipate that my research will have broad impact in the understanding of gene regulation, the origin of altered epigenetic marking and the influence of these alterations on cancer.

Education & Training

Degree-Granting Education

2003 Sao Paulo State Universtiy, Sao Jose do Rio Preto, SP, Brazil, PHD, Genetics
1999 Sao Paulo State Universtiy, Sao Jose do Rio Preto, SP, Brazil, MS, Biology
1996 Sao Paulo State University, Sao Jose do Rio Preto, SP, Brazil, BS, Biology

Postgraduate Training

7/2003-4/2007 Research Fellowship, Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, Jean-Pierre Issa


Academic Appointments

Assistant Professor, Department of Biochemistry and Molecular Biology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 9/2011-8/2012
Assistant Professor, Department of Leukemia - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 6/2011-8/2011
Instructor, Department of Leukemia - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 5/2007-5/2011

Honors and Awards

2006 Keystone Symposia Scholarship, Keyston Symposia and National Institute of Health
2005 AACR Minority Scholar Awards in Cancer Research, American Association for Cancer Research and National Institute of Health USA
2001 ASTRA/ZENECA Scholar-in-Training Travel Award, ASTRA/ZENECA and American Association of Cancer Research
1997 Health Care Professionals Award, Sao Jose do Rio Preto Medical School
1994-1996 Dean's List, Sao Paulo State University

Selected Publications

Peer-Reviewed Original Research Articles

1. Carugo A, Genovese G, Seth S, Nezi L, Rose JL, Bossi D, Cicalese A, Shah PK, Viale A, Pettazzoni PF, Akdemir KC, Bristow CA, Robinson FS, Tepper J, Sanchez N, Gupta S, Estecio MR, Giuliani V, Dellino GI, Riva L, Yao W, Di Francesco ME, Green T, D'Alesio C, Corti D, Kang Y, Jones P, Wang H, Fleming JB, Maitra A, Pelicci PG, Chin L, DePinho RA, Lanfrancone L, Heffernan TP, Draetta GF. In Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer. Cell Rep 16(1):133-47, 6/2016. e-Pub 6/2016. PMID: 27320920.
2. Rossi EL, de Angel RE, Bowers LW, Khatib SA, Smith LA, Van Buren E, Bhardwaj P, Giri D, Estecio MR, Troester MA, Hair BY, Kirk EL, Gong T, Shen J, Dannenberg AJ, Hursting SD. Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice. Cancer Prev Res (Phila) 9(5):339-48, 5/2016. e-Pub 2/2016. PMCID: PMC4854773.
3. Kleb B, Estécio MR, Zhang J, Tzelepi V, Chung W, Jelinek J, Navone NM, Tahir S, Marquez VE, Issa JP, Maity S, Aparicio A. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas. Epigenetics 11(3):184-93, 3/2016. e-Pub 2/2016. PMCID: PMC4854553.
4. Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, Parmar S, Cortes J, Kantarjian H, Garcia-Manero G. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28(6):1280-8, 6/2014. e-Pub 11/2013. PMCID: PMC4032802.
5. Jin C, Lu Y, Jelinek J, Liang S, Estecio MR, Barton MC, Issa JP. TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells. Nucleic Acids Res. e-Pub 5/2014. PMCID: PMC4066785.
6. Maegawa S, Gough SM, Watanabe-Okochi N, Lu Y, Zhang N, Castoro RJ, Estecio MR, Jelinek J, Liang S, Kitamura T, Aplan PD, Issa JP. Age-related epigenetic drift in the pathogenesis of MDS and AML. Genome Res 24(4):580-91, 4/2014. e-Pub 1/2014. PMCID: PMC3975058.
7. Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, Jelinek J, Yamano HO, Sugai T, An B, Shureiqi I, Toyota M, Kondo Y, Estecio MR, Issa JP. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 74(5):1311-8, 3/2014. e-Pub 1/2014. PMCID: PMC4396185.
8. Tahara T, Yamamoto E, Madireddi P, Suzuki H, Maruyama R, Chung W, Garriga J, Jelinek J, Yamano HO, Sugai T, Kondo Y, Toyota M, Issa JP, Estécio MR. Colorectal Carcinomas with CpG Island Methylator Phenotype 1 Frequently Contain Mutations in Chromatin Regulators. Gastroenterology 146(2):530-38.e5, 2/2014. e-Pub 11/2013. PMCID: PMC3918446.
9. Malouf GG, Taube JH, Lu Y, Roysarkar T, Panjarian S, Estécio MR, Jelinek J, Yamazaki J, Raynal NJ, Long H, Tahara T, Tinnirello A, Ramachandran P, Zhang XY, Liang S, Mani SA, Issa JP. Architecture of epigenetic reprogramming following Twist1-mediated epithelial-mesenchymal transition. Genome Biol 14(12). e-Pub 12/2013. PMCID: PMC4053791.
10. Tahara T, Maegawa S, Chung W, Garriga J, Jelinek J, Estecio MR, Shibata T, Hirata I, Arisawa T, Issa JP. Examination of whole blood DNA methylation as a potential risk marker for gastric cancer. Cancer Prev Res (Phila) 6(10):1093-100, 10/2013. e-Pub 8/2013. PMCID: PMC4337829.
11. Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis RS, Nishida N, Gafŕ R, Song J, Guo Z, Ivan C, Barbarotto E, De Vries I, Zhang X, Ferracin M, Churchman M, van Galen JF, Beverloo BH, Shariati M, Haderk F, Estecio MR, Garcia-Manero G, Patijn GA, Gotley DC, Bhardwaj V, Shureiqi I, Sen S, Multani AS, Welsh J, Yamamoto K, Taniguchi I, Song MA, Gallinger S, Casey G, Thibodeau SN, Le Marchand L, Tiirikainen M, Mani SA, Zhang W, Davuluri RV, Mimori K, Mori M, Sieuwerts AM, Martens JW, Tomlinson I, Negrini M, Berindan-Neagoe I, Foekens JA, Hamilton SR, Lanza G, Kopetz S, Fodde R, Calin GA. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res 23(9):1446-61, 9/2013. e-Pub 6/2013. PMCID: PMC3759721.
12. Yamazaki J, Estécio MR, Lu Y, Long H, Malouf GG, Graber D, Huo Y, Ramagli L, Liang S, Kornblau SM, Jelinek J, Issa JP. The epigenome of AML stem and progenitor cells. Epigenetics 8(1):92-104, 1/2013. e-Pub 12/2012. PMCID: PMC3549884.
13. Jelinek J, Liang S, Lu Y, He R, Ramagli LS, Shpall EJ, Estécio MR, Issa JP. Conserved DNA methylation patterns in healthy blood cells and extensive changes in leukemia measured by a new quantitative technique. Epigenetics 7(12):1368-78, 12/2012. e-Pub 10/2012. PMCID: PMC3528692.
14. Estécio MR, Gallegos J, Dekmezian M, Lu Y, Liang S, Issa JP. SINE Retrotransposons Cause Epigenetic Reprogramming of Adjacent Gene Promoters. Mol Cancer Res 10(10):1332-42, 10/2012. e-Pub 9/2012. PMCID: PMC3475755.
15. Zhang Y, Shu J, Si J, Shen L, Estécio MR, Issa JP. Repetitive elements and enforced transcriptional repression co-operate to enhance DNA methylation spreading into a promoter CpG-island. Nucleic Acids Res 40(15):7257-68, 8/2012. e-Pub 5/2012. PMCID: PMC3424568.
16. Raynal NJ, Si J, Taby RF, Gharibyan V, Ahmed S, Jelinek J, Estécio MR, Issa JP. DNA methylation does not stably lock gene expression but instead serves as a molecular mark for gene silencing memory. Cancer Res 72(5):1170-81, 3/2012. e-Pub 1/2012. PMCID: PMC3294136.
17. Yamazaki J, Taby R, Vasanthakumar A, Macrae T, Ostler KR, Shen L, Kantarjian HM, Estécio MR, Jelinek J, Godley LA, Issa JP. Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia. Epigenetics 7(2):201-7, 2/2012. PMCID: PMC3335912.
18. Jelinek J, Gharibyan V, Estécio MR, Kondo K, He R, Chung W, Lu Y, Zhang N, Liang S, Kantarjian HM, Cortes JE, Issa JP. Aberrant DNA methylation is associated with disease progression, resistance to imatinib and shortened survival in chronic myelogenous leukemia. PLoS One 6(7):e22110, 2011. e-Pub 7/2011. PMCID: PMC3132778.
19. Watanabe Y, Castoro RJ, Kim HS, North B, Oikawa R, Hiraishi T, Ahmed SS, Chung W, Cho MY, Toyota M, Itoh F, Estécio MR, Shen L, Jelinek J, Issa JP. Frequent Alteration of MLL3 Frameshift Mutations in Microsatellite Deficient Colorectal Cancer. PLoS One 6(8):e23320, 2011. e-Pub 8/2011. PMCID: PMC3154922.
20. Estécio MR, Gallegos J, Vallot C, Castoro RJ, Chung W, Maegawa S, Oki Y, Kondo Y, Jelinek J, Shen L, Hartung H, Aplan PD, Czerniak BA, Liang S, Issa JP. Genome Architecture Marked by Retrotransposons Modulates Predisposition to DNA Methylation in Cancer. Genome Res 20(10):1369-1382, 10/2010. e-Pub 8/2010. PMCID: PMC2945186.
21. Estecio MR, Yan PS, Ibrahim AE, Tellez CS, Shen L, Huang TH, Issa JP. High throughput methylation profiling by MCA coupled to CpG island microarray. Genome Res 17(10):1529-1536, 10/2007. e-Pub 9/2007. PMID: 17785535.
22. Estecio MRH, Gharibyan V, Shen L, Ibrahim AE, Doshi K, He R, Jelinek J, Yang AS, Yan PS, Huang TH, Tajara EH, Issa JP. LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability. PLoS ONE 2(5):399, 5/2007. PMID: 17476321.
23. Estecio MR, Youssef EM, Rahal P, Fukuyama EE, Gois-Filho JF, Maniglia JV, Goloni-Bertollo EM, Issa JP, Tajara EH. LHX6 is a sensitive methylation marker in head and neck carcinomas. Oncogene 25(36):5018-26, 8/2006. PMID: 16732332.
24. Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, Issa JP. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 32(3):38, 2/2004. PMID: 14973332.
25. Yang AS, Estecio MR, Garcia-Manero G, Kantarjian HM, Issa JP. Comment on "Chromosomal instability and tumors promoted by DNA hypomethylation" and "Induction of tumors in nice by genomic hypomethylation". Science 302(5648):1153, 11/2003. PMID: 14615517.

Invited Articles

1. Estécio MR, Issa JP. Dissecting DNA hypermethylation in cancer. FEBS Lett 585(13):2078-86, 7/7/2011. e-Pub 12/10/2010. PMCID: PMC3378045.
2. Estécio MR, Issa JP. Tackling the methylome: recent methodological advances in genome-wide methylation profiling. Genome Med 1(11):106, 2009. e-Pub 11/16/2009. PMCID: PMC2808741.
3. Estécio MR, Yan PS, Huang TH, Issa JP. Methylated CpG island amplification and microarray (MCAM) for high-throughput analysis of DNA methylation. CSH Protoc 3(3):pdb.prot4974,, 2008. e-Pub 3/1/2008. PMID: 21356790.

Last updated: 7/27/2016