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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)

26260954. Issa JP, Gonzaga M, Kotake BG, de Lucia C, Ervolino E, Iyomasa M, Bone repair of critical size defects treated with autogenic, allogenic, or xenogenic bone grafts alone or in combination with rhBMP-2. Clin Oral Implants Res :()2015 Aug 11

26224146. Malouf GG, Tahara T, Paradis V, Fabre M, Guettier C, Yamazaki J, Long H, Lu Y, Raynal NJ, Jelinek J, Mouawad R, Khayat D, Brugières L, Raymond E, Issa JP, Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts distinctive features. Epigenetics 10:9(872-81)2015 Sep 2

26211600. Tefferi A, Kantarjian H, Rajkumar SV, Baker LH, Abkowitz JL, Adamson JW, Advani RH, Allison J, Antman KH, Bast RC Jr, Bennett JM, Benz EJ Jr, Berliner N, Bertino J, Bhatia R, Bhatia S, Bhojwani D, Blanke CD, Bloomfield CD, Bosserman L, Broxmeyer HE, Byrd JC, Cabanillas F, Canellos GP, Chabner BA, Chanan-Khan A, Cheson B, Clarkson B, Cohn SL, Colon-Otero G, Cortes J, Coutre S, Cristofanilli M, Curran WJ Jr, Daley GQ, DeAngelo DJ, Deeg HJ, Einhorn LH, Erba HP, Esteva FJ, Estey E, Fidler IJ, Foran J, Forman S, Freireich E, Fuchs C, George JN, Gertz MA, Giralt S, Golomb H, Greenberg P, Gutterman J, Handin RI, Hellman S, Hoff PM, Hoffman R, Hong WK, Horowitz M, Hortobagyi GN, Hudis C, Issa JP, Johnson BE, Kantoff PW, Kaushansky K, Khayat D, Khuri FR, Kipps TJ, Kripke M, Kyle RA, Larson RA, Lawrence TS, Levine R, Link MP, Lippman SM, Lonial S, Lyman GH, Markman M, Mendelsohn J, Meropol NJ, Messinger Y, Mulvey TM, O'Brien S, Perez-Soler R, Pollock R, Prchal J, Press O, Radich J, Rai K, Rosenberg SA, Rowe JM, Rugo H, Runowicz CD, Sandmaier BM, Saven A, Schafer AI, Schiffer C, Sekeres MA, Silver RT, Siu LL, Steensma DP, Stewart FM, Stock W, Stone R, Storb R, Strong LC, Tallman MS, Thompson M, Ueno NT, Van Etten RA, Vose JM, Wiernik PH, Winer EP, Younes A, Zelenetz AD, LeMaistre CA, In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs. Mayo Clin Proc 90:8(996-1000)2015 Aug

26210684. Paliologo T, Shimano RC, Shimano AC, Macedo AP, Falcai MJ, Issa JP, Effects of swimming associated with risedronate in osteopenic bones: An experimental study with ovariectomized rats. Micron 78:(40-44)2015 Jul 10

26179081. Volpon JB, Silva AV, Falcai MJ, Louzada MJ, Zamarioli A, Kotake BG, Issa JP, The osteogenic effects of swimming on bone mass, strength, and microarchitecture in rats with unloading-induced bone loss. Microsc Res Tech 78:9(784-91)2015 Sep

26053038. Iyomasa MM, Fernandes FS, Iyomasa DM, Pereira YC, Fernández RA, Calzzani RA, Nascimento GC, Leite-Panissi CR, Issa JP, Metabolic Changes in Masseter Muscle of Rats Submitted to Acute Stress Associated with Exodontia. PLoS One 10:6(e0128397)2015

25972343. Yamazaki J, Jelinek J, Lu Y, Cesaroni M, Madzo J, Neumann F, He R, Taby R, Vasanthakumar A, Macrae T, Ostler KR, Kantarjian HM, Liang S, Estecio MR, Godley LA, Issa JP, TET2 Mutations Affect Non-CpG Island DNA Methylation at Enhancers and Transcription Factor-Binding Sites in Chronic Myelomonocytic Leukemia. Cancer Res 75:14(2833-43)2015 Jul 15

25925228. Dos S Kotake BG, Salzedas LM, Ervolino E, Calzzani RA, Sebald W, Issa JP, Bone Recuperation After rhBMP-2 Insertion in Alcoholic Animals-Experimental Study. Curr Pharm Des 21:24(3557-64)2015

25874255. Pedrazzi V, Leite MF, Tavares RC, Sato S, do Nascimento GC, Issa JP, Herbal mouthwash containing extracts of Baccharis dracunculifolia as agent for the control of biofilm: clinical evaluation in humans. ScientificWorldJournal 2015:(712683)2015

25874243. Kurita Varoli F, Sucena Pita M, Sato S, Issa JP, do Nascimento C, Pedrazzi V, Analgesia evaluation of 2 NSAID drugs as adjuvant in management of chronic temporomandibular disorders. ScientificWorldJournal 2015:(359152)2015

25831100. Pedrazzi V, Corsi LP, Pedrazzi H, Netto EI, Nascimento Cd, Issa JP, Clinical evaluation of residual tetrasodium pyrophosphate released from two different anticalculus flosses. Braz Dent J 26:2(116-20)2015 Mar-Apr

25825118. Machado EG, Issa JP, Figueiredo FA, Santos GR, Galdeano EA, Alves MC, Chacon EL, Ferreira Junior RS, Barraviera B, Cunha MR, A new heterologous fibrin sealant as scaffold to recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins for the repair of tibial bone defects. Acta Histochem 117:3(288-96)2015 Apr

25806091. Tsimberidou AM, Said R, Culotta K, Wistuba I, Jelinek J, Fu S, Falchook G, Naing A, Piha-Paul S, Zinner R, Siddik ZH, He G, Hess K, Stewart DJ, Kurzrock R, Issa JP, Phase I study of azacitidine and oxaliplatin in patients with advanced cancers that have relapsed or are refractory to any platinum therapy. Clin Epigenetics 7:1(29)2015

25798995. Issa JP, Ingraci de Lucia C, Dos Santos Kotake BG, Gonçalves Gonzaga M, Tocchini de Figueiredo FA, Mizusaki Iyomasa D, Macedo AP, Ervolino E, The effect of simvastatin treatment on bone repair of femoral fracture in animal model. Growth Factors 33:2(139-48)2015 Apr

25677810. Muniz KL, Dias FJ, Coutinho-Netto J, Calzzani RA, Iyomasa MM, Sousa LG, Santos TT, Teles VO, Watanabe IS, Fazan VP, Issa JP, Properties of the tibialis anterior muscle after treatment with laser therapy and natural latex protein following sciatic nerve crush. Muscle Nerve :()2015 Feb 9

25619570. Dias FJ, Issa JP, Coutinho-Netto J, Fazan VP, Sousa LG, Iyomasa MM, Papa PC, Watanabe IS, Morphometric and high resolution scanning electron microscopy analysis of low-level laser therapy and latex protein (Hevea brasiliensis) administration following a crush injury of the sciatic nerve in rats. J Neurol Sci 349:1-2(129-37)2015 Feb 15

25455458. van Esterik JC, Vitins AP, Hodemaekers HM, Kamstra JH, Legler J, Pennings JL, Steegenga WT, Lute C, Jelinek J, Issa JP, Dollé ME, van der Ven LT, Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A. Toxicol Lett 232:1(293-300)2014 Oct 17

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 121:4(556-61)2015 Feb 15

25257251. Barreiros VC, Dias FJ, Iyomasa MM, Coutinho-Netto J, de Sousa LG, Fazan VP, Antunes Rde S, Watanabe IS, Issa JP, Morphological and morphometric analyses of crushed sciatic nerves after application of a purified protein from natural latex and hyaluronic acid hydrogel. Growth Factors 32:5(164-70)2014 Oct

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

25028660. Guerra Cde S, Carla Lara Pereira Y, Issa JP, Luiz KG, Guimarães EA, Gerlach RF, Iyomasa MM, Histological, histochemical, and protein changes after induced malocclusion by occlusion alteration of Wistar rats. Biomed Res Int 2014:(563463)2014

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

24974977. Azevedo A, Prado AF, Antonio RC, Issa JP, Gerlach RF, Matrix metalloproteinases are involved in cardiovascular diseases. Basic Clin Pharmacol Toxicol 115:4(301-14)2014 Oct

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 Jun

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

24800241. de Figueiredo FA, Gerlach RF, da Veiga MA, Nakadi FV, Ramos J, Kawakita ER, Guerra Cde S, Issa JP, Reduced bone and body mass in young male rats exposed to lead. Biomed Res Int 2014:(571065)2014

24692117. Shimano RC, Macedo AP, Falcai MJ, Ervolino E, Shimano AC, Issa JP, Biomechanical and microstructural benefits of physical exercise associated with risedronate in bones of ovariectomized rats. Microsc Res Tech 77:6(431-8)2014 Jun

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 ß-linked 2-deoxy-sugars. J Am Chem Soc 136:15(5740-4)2014 Apr 16

24616895. Iyomasa MM, Leão JC, Rizzi ÉC, Issa JP, Dias FJ, Watanabe IS, Iyomasa DM, Ultrastructure and light microscope analysis of intact skin after a varying number of low level laser irradiations in mice. Biomed Res Int 2014:(506051)2014

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, Estécio 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

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, Estécio 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

24123452. Watanabe IS, Ogawa K, Cury DP, Dias FJ, Sosthenes MC, Issa JP, Iyomasa MM, Fine structure of bacterial adhesion to the epithelial cell membranes of the filiform papillae of tongue and palatine mucosa of rodents: a morphometric, TEM, and HRSEM study. Microsc Res Tech 76:12(1226-33)2013 Dec

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, Estécio 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

23936823. Dias FJ, Issa JP, Iyomasa MM, Coutinho-Netto J, Calzzani RA, Iyomasa DM, Sousa LG, de Almeida SR, Cury DP, Watanabe IS, Application of a low-level laser therapy and the purified protein from natural latex (Hevea brasiliensis) in the controlled crush injury of the sciatic nerve of rats: a morphological, quantitative, and ultrastructural study. Biomed Res Int 2013:(597863)2013

23906042. Issa JP, Lloyd D, Steliotes E, Bennett CS, Reagent controlled ß-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, ß-Thalassemia due to intronic LINE-1 insertion in the ß-globin gene (HBB): molecular mechanisms underlying reduced transcript levels of the ß-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

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