Jean Pierre Issa, M.D.

1987, American University of Beirut

UT M. D. Anderson Cancer Center
Leukemia

Research Interests: Epigenetics and silencing; DNA methylation in normal and neoplastic cells; molecular biology of aging and cancer; tumor-suppressor genes; epigenetic therapy and translational research

My laboratory is involved in both basic and translational research in the field of molecular epigenetics. Specifically, we are interested in a DNA modification termed DNA methylation that is commonly abnormal in aging tissues and in various malignancies. Current projects include:

1. Cloning and functional analysis of genes differentially methylated in specific cancers.

2. Investigating the causes of aberrant methylation in cancer, focusing on aging, a particular hypermethylator phenotype we described called CpG Island methylator phenotype, environmental exposures and familial predisposition.

3. Studying the causes and consequences of DNA methylation changes in normal aging tissues. Does reducing methylation prevent tumor formation and prolong lifespan?

4.Clinical implications of methylation profiling in cancer. Can we identify subgroups with particular characteristics, prognosis, etc.?

5. 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?

A tutorial in my laboratory would introduce students to the study of DNA methylation and, depending on interest, would expose students to gene cloning, translational research, molecular (epigenetic/genetic/chromatin) analysis of aging and neoplastic cells and tissues and transcriptional gene regulation.
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Recent reviews:

Issa, JP (2005) DNA methylation in the treatment of hematologic malignancies. Clin. Adv. Hematol. Oncol. 3, 684-686.

Toyota M and Issa JP (2005) Epigenetic changes in solid and hematopoietic tumors. Semin. Oncol. 32, 521-530.

Kondo Y and Issa JP (2004) Epigenetic changes in colorectal cancer. Cancer Metastasis Rev. 23, 29-39.

Issa JP (2004) CpG island methylator phenotype in cancer. Nat. Rev. Cancer 4, 988-993.

Issa JP (2003) Age-related epigenetic changes and the immune system. Clin. Immunol. 109, 103-108.

Issa JP (2002) Epigenetic variation and human disease. J. Nutr. 132, 2388S-2392S.

SantiniV, Kantarjian HM and Issa JP (2001) Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann. Intern. Med. 134, 573-586.

Some key and recent publications:

Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE and Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat. Genet. 7, 536-540.

Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB and Issa JPJ (1999) CpG Island Methylator Phenotype in Colorectal Cancer. Proc. Natl. Acad. Sci. U. S. A. 96, 8681-8686.

Kondo Y, Shen L and Issa JP (2003) Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer. Mol. Cell Biol. 23, 206-215.

Kondo Y, Shen L, Yan PS, Huang TH and Issa JP (2004) Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation. Proc Natl Acad Sci U S A 101, 7398-7403.

Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J and Kantarjian HM (2004) Phase I study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (Decitabine) in hematopoietic malignancies. Blood 103, 1635-1640.

Yang AS, Doshi KD, Choi SW, Mason JB, Mannari RK, Gharybian V, Luna R, Rashid A, Shen L, Estecio MR, Kantarjian HM, Garcia-Manero G. and Issa JP (2006) DNA methylation changes after 5-aza-2'-deoxycytidine therapy in patients with leukemia. Cancer Res 66, 5495-5503.

Shu J, Jelinek J, Chang H, Shen L, Qin T, Chung W, Oki Y and Issa JP (2006) Silencing of bidirectional promoters by DNA methylation in tumorigenesis. Cancer Res 66, 5077-5084.

Program Affiliation:
Program in Cancer Biology