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Jean-Pierre Issa, MD

Jean-Pierre Issa, MD

 

Professor, Medicine

Director, Fels Institute for Cancer Research and Molecular Biology

3307 North Broad Street, Room 154 (Allied Health Building)

Telephone:  215-707-4307

Email: jpissa@temple.edu

 

Fels Institute for Cancer Research and Molecular Biology

Department of Medicine, Section of Oncology

 

Educational Background:

 

BS, The American University of Beirut, Beirut, Lebanon, 1983

 

MD, The American University of Beirut, Beirut, Lebanon, 1987

 

Residency, Internal Medicine, The Good Samaritan Hospital, Baltimore, MD, 1987-1990

 

Fellowship, Medical Oncology, The Johns Hopkins University, Baltimore, MD, 1990-1994

 

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clinical Interests:

 
  • Leukemias

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board certification(s):

 

  • Internal Medicine, 1990
  • Medical oncology, 1993
 

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Research Interests:

 

  • Epigenomics and genomics in normal, aging and cancer cells (DNA methylation and histone modifications; genome wide genetic changes)
  • Basic mechanisms in epigenetics
  • Tumor-suppressor genes
  • Translational studies in cancer
  • Pre-clinical and clinical research in epigenetic therapy

My laboratory is involved in both basic and translational research in the field of molecular epigenetics, which refers to stable gene expression states such as X-inactivation, imprinting etc. Specifically, we are interested in epigenetic mechanisms - a DNA modification termed DNA methylation that is commonly abnormal in aging tissues and in various malignancies; and histone modifications involved in determining gene expression states.

 

Current projects include:

  • Large scale mapping of epigenomics patterns in normal, aging and cancer cells
  • Investigating the causes of aberrant methylation in cancer, focusing on aging; genetic changes; a particular hypermethylator phenotype we described called CpG Island methylator phenotype; environmental exposures and familial predisposition
  • Basic mechanisms governing the establishment of DNA methylation in normal and cancer cells
  • Studying the causes and consequences of DNA methylation changes in normal aging tissues. Does reducing methylation prevent tumor formation and prolong lifespan?
  • Clinical implications of methylation profiling in cancer. Can we identify subgroups with particular characteristics, prognosis, etc.?
  • Clinical trials of drugs that affect histone modifications and DNA methylation are ongoing. Can we predict who will respond to the drugs? Can we make the therapy better? Does it work the way it is supposed to?
  • Screens for drugs that affect epigenetics, alone or in synergy with current FDA approved molecules.

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AWARDS AND HONORS:

 

  • Rosenthal Award, American Association for Cancer Research, 2011
  • Faculty Achievement Award in Basic Research, M. D. Anderson Cancer Center, 2007
  • American Cancer Society Clinical Research Professorship, 2007
  • Frei Award in Translational Research from the Division of Cancer Medicine, M. D. Anderson Cancer Center, 2006
  • Election to American Society of Clinical Investigation, 2003
  • Sidney Kimmel Foundation Scholar Award, 1997

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25336333. Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, Borthakur G, Brandt M, Pierce S, Kantarjian HM, Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer :()2014 Oct 21

25040094. Kirschbaum M, Gojo I, Goldberg SL, Bredeson C, Kujawski LA, Yang A, Marks P, Frankel P, Sun X, Tosolini A, Eid JE, Lubiniecki GM, Issa JP, A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. Br J Haematol 167:2(185-93)2014 Oct

25024751. Stewart DJ, Nunez MI, Jelinek J, Hong D, Gupta S, Aldaz M, Issa JP, Kurzrock R, Wistuba II, Impact of decitabine on immunohistochemistry expression of the putative tumor suppressor genes FHIT, WWOX, FUS1 and PTEN in clinical tumor samples. Clin Epigenetics 6:1(13)2014

24876104. Cui Y, Hausheer F, Beaty R, Zahnow C, Issa JP, Bunz F, Baylin SB, A recombinant reporter system for monitoring reactivation of an endogenously DNA hypermethylated gene. Cancer Res 74:14(3834-43)2014 Jul 15

24875481. 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 42:11(6956-71)2014

24875133. Plimack ER, Desai JR, Issa JP, Jelinek J, Sharma P, Vence LM, Bassett RL, Ilagan JL, Papadopoulos NE, Hwu WJ, A phase I study of decitabine with pegylated interferon a-2b in advanced melanoma: impact on DNA methylation and lymphocyte populations. Invest New Drugs 32:5(969-75)2014 Oct

24670685. Pathiraja TN, Nayak SR, Xi Y, Jiang S, Garee JP, Edwards DP, Lee AV, Chen J, Shea MJ, Santen RJ, Gannon F, Kangaspeska S, Jelinek J, Issa JP, Richer JK, Elias A, McIlroy M, Young LS, Davidson NE, Schiff R, Li W, Oesterreich S, Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer. Sci Transl Med 6:229(229ra41)2014 Mar 26

24670112. Issa JP, Bennett CS, A reagent-controlled SN2-glycosylation for the direct synthesis of ▀-linked 2-deoxy-sugars. J Am Chem Soc 136:15(5740-4)2014 Apr 16

24414704. 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)2014 Apr

24401732. Stewart DJ, Nunez MI, Jelinek J, Hong D, Gupta S, Issa JP, Wistuba II, Kurzrock R, Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors. Clin Epigenetics 6:1(2)2014 Jan 9

24385213. 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, EstÚcio MR, Issa JP, Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 74:5(1311-8)2014 Mar 1

24382386. Issa JP, Aging and epigenetic drift: a vicious cycle. J Clin Invest 124:1(24-9)2014 Jan 2

24367927. Malouf GG, Taube JH, Lu Y, Roysarkar T, Panjarian S, Estecio 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(R144)2013 Dec 24

24211491. 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, EstÚcio MR, Colorectal carcinomas with CpG island methylator phenotype 1 frequently contain mutations in chromatin regulators. Gastroenterology 146:2(530-38.e5)2014 Feb

24184133. Okamoto Y, Shinjo K, Shimizu Y, Sano T, Yamao K, Gao W, Fujii M, Osada H, Sekido Y, Murakami S, Tanaka Y, Joh T, Sato S, Takahashi S, Wakita T, Zhu J, Issa JP, Kondo Y, Hepatitis virus infection affects DNA methylation in mice with humanized livers. Gastroenterology 146:2(562-72)2014 Feb

24045437. Taube JH, Malouf GG, Lu E, Sphyris N, Vijay V, Ramachandran PP, Ueno KR, Gaur S, Nicoloso MS, Rossi S, Herschkowitz JI, Rosen JM, Issa JP, Calin GA, Chang JT, Mani SA, Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties. Sci Rep 3:(2687)2013

23943784. Tahara T, Maegawa S, Chung W, Garriga J, Jelinek J, EstÚcio 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)2013 Oct

23906042. Issa JP, Lloyd D, Steliotes E, Bennett CS, Reagent controlled ▀-specific dehydrative glycosylation reactions with 2-deoxy-sugars. Org Lett 15:16(4170-3)2013 Aug 16

23878091. Lanikova L, Kucerova J, Indrak K, Divoka M, Issa JP, Papayannopoulou T, Prchal JT, Divoky V, ▀-Thalassemia due to intronic LINE-1 insertion in the ▀-globin gene (HBB): molecular mechanisms underlying reduced transcript levels of the ▀-globin(L1) allele. Hum Mutat 34:10(1361-5)2013 Oct

23720055. Natsume A, Ito M, Katsushima K, Ohka F, Hatanaka A, Shinjo K, Sato S, Takahashi S, Ishikawa Y, Takeuchi I, Shimogawa H, Uesugi M, Okano H, Kim SU, Wakabayashi T, Issa JP, Sekido Y, Kondo Y, Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma. Cancer Res 73:14(4559-70)2013 Jul 15

23660859. Issa JP, The myelodysplastic syndrome as a prototypical epigenetic disease. Blood 121:19(3811-7)2013 May 9

23619168. Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, Zhao M, Ortega Alves MV, Chang K, Drummond J, Cortez E, Xie TX, Zhang D, Chung W, Issa JP, Zweidler-McKay PA, Wu X, El-Naggar AK, Weinstein JN, Wang J, Muzny DM, Gibbs RA, Wheeler DA, Myers JN, Frederick MJ, Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 3:7(770-81)2013 Jul

23249680. Yamazaki J, Estecio 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)2013 Jan

23188507. Beck S, Bernstein BE, Campbell RM, Costello JF, Dhanak D, Ecker JR, Greally JM, Issa JP, Laird PW, Polyak K, Tycko B, Jones PA, A blueprint for an international cancer epigenome consortium. A report from the AACR Cancer Epigenome Task Force. Cancer Res 72:24(6319-24)2012 Dec 15

23075513. Jelinek J, Liang S, Lu Y, He R, Ramagli LS, Shpall EJ, Estecio 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)2012 Dec 1

23054654. Yamazaki J, Issa JP, Epigenetic aspects of MDS and its molecular targeted therapy. Int J Hematol 97:2(175-82)2013 Feb

22952045. EstÚcio 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)2012 Oct

22869041. Ulrich CM, Toriola AT, Koepl LM, Sandifer T, Poole EM, Duggan C, McTiernan A, Issa JP, Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women. Epigenetics 7:9(1020-8)2012 Sep

22695491. Xu J, Shetty PB, Feng W, Chenault C, Bast RC Jr, Issa JP, Hilsenbeck SG, Yu Y, Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome. BMC Cancer 12:(243)2012 Jun 13

22665218. Boumber Y, Kantarjian H, Jorgensen J, Wen S, Faderl S, Castoro R, Autry J, Garcia-Manero G, Borthakur G, Jabbour E, Estrov Z, Cortes J, Issa JP, Ravandi F, A randomized study of decitabine versus conventional care for maintenance therapy in patients with acute myeloid leukemia in complete remission. Leukemia 26:11(2428-31)2012 Nov

22600741. Zhang Y, Shu J, Si J, Shen L, Estecio 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)2012 Aug

22564986. Issa JP, DNA methylation as a clinical marker in oncology. J Clin Oncol 30:20(2566-8)2012 Jul 10

22439938. Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA, Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell 21:3(430-46)2012 Mar 20

22395470. Yamazaki J, Taby R, Vasanthakumar A, Macrae T, Ostler KR, Shen L, Kantarjian HM, Estecio MR, Jelinek J, Godley LA, Issa JP, Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia. Epigenetics 7:2(201-7)2012 Feb

22322598. Bhardwaj A, Song HW, Beildeck M, Kerkhofs S, Castoro R, Shanker S, De Gendt K, Suzuki K, Claessens F, Issa JP, Orgebin-Crist MC, Wilkinson MF, DNA demethylation-dependent AR recruitment and GATA factors drive Rhox5 homeobox gene transcription in the epididymis. Mol Endocrinol 26:4(538-49)2012 Apr

22219169. Raynal NJ, Si J, Taby RF, Gharibyan V, Ahmed S, Jelinek J, EstÚcio 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)2012 Mar 1

22138693. Challen GA, Sun D, Jeong M, Luo M, Jelinek J, Berg JS, Bock C, Vasanthakumar A, Gu H, Xi Y, Liang S, Lu Y, Darlington GJ, Meissner A, Issa JP, Godley LA, Li W, Goodell MA, Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet 44:1(23-31)2011 Dec 4

22132162. Konishi K, Watanabe Y, Shen L, Guo Y, Castoro RJ, Kondo K, Chung W, Ahmed S, Jelinek J, Boumber YA, Estecio MR, Maegawa S, Kondo Y, Itoh F, Imawari M, Hamilton SR, Issa JP, DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. PLoS One 6:11(e27889)2011

21858090. Qin T, Castoro R, El Ahdab S, Jelinek J, Wang X, Si J, Shu J, He R, Zhang N, Chung W, Kantarjian HM, Issa JP, Mechanisms of resistance to decitabine in the myelodysplastic syndrome. PLoS One 6:8(e23372)2011

21853109. Watanabe Y, Castoro RJ, Kim HS, North B, Oikawa R, Hiraishi T, Ahmed SS, Chung W, Cho MY, Toyota M, Itoh F, Estecio MR, Shen L, Jelinek J, Issa JP, Frequent alteration of MLL3 frameshift mutations in microsatellite deficient colorectal cancer. PLoS One 6:8(e23320)2011

21792236. Issa JP, Epigenetic variation and cellular Darwinism. Nat Genet 43:8(724-6)2011 Jul 27

21761494. Do Prado Ribeiro DC, de Abreu Figueira L, Issa JP, Dias Vecina CA, JosÚdias F, Da Cunha MR, Study of the osteoconductive capacity of hydroxyapatite implanted into the femur of ovariectomized rats. Microsc Res Tech 75:2(133-7)2012 Feb

21761492. Iyomasa MM, Issa JP, de Queirˇz Tavares ML, Pereira YC, Stuani MB, Mishima F, Coutinho-Netto J, Sebald W, Influence of low-level laser associated with osteogenic proteins recombinant human BMP-2 and Hevea brasiliensis on bone repair in Wistar rats. Microsc Res Tech 75:2(117-25)2012 Feb

21760961. Jelinek J, Gharibyan V, Estecio 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

21693122. Issa JP, Just W, Epigenetics. FEBS Lett 585:13(1993)2011 Jul 7

21586619. Chung W, Bondaruk J, Jelinek J, Lotan Y, Liang S, Czerniak B, Issa JP, Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments. Cancer Epidemiol Biomarkers Prev 20:7(1483-91)2011 Jul

21548464. Boumber Y, Issa JP, Epigenetics in cancer: what's the future? Oncology (Williston Park) 25:3(220-6, 228)2011 Mar

21509761. Ahn JB, Chung WB, Maeda O, Shin SJ, Kim HS, Chung HC, Kim NK, Issa JP, DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer 117:9(1847-54)2011 May 1

21459801. Pathiraja TN, Shetty PB, Jelinek J, He R, Hartmaier R, Margossian AL, Hilsenbeck SG, Issa JP, Oesterreich S, Progesterone receptor isoform-specific promoter methylation: association of PRA promoter methylation with worse outcome in breast cancer patients. Clin Cancer Res 17:12(4177-86)2011 Jun 15

21439246. Cogdell D, Chung W, Liu Y, McDonald JM, Aldape K, Issa JP, Fuller GN, Zhang W, Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma. Chin J Cancer 30:4(247-53)2011 Apr

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