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 Centre for Addictionand Mental Health |
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Research
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Epigenomics
Welcome to the Krembil Family Epigenetics Laboratory. This laboratory was established in 2002 through the generous donation of the Krembil Foundation, in collaboration with the Foundation of the Centre for Addiction and Mental Health. The purpose and long term objective of our research is to understand if and how epigenetic modifications of DNA and chromosomal proteins histones can predispose and/or cause severe human diseases such as schizophrenia, bipolar disease, and major depression.
Psychiatric epigenomics. Over the past 100 years psychiatric diseases have been investigated using epidemiologic, psychoanalytical, clinical, genetic, pharmacological, and neurochemical approaches. All this work led to numerous exciting findings, however, the mechanisms and causes of psychiatric diseases still remain unclear. It is now evident that innovative ideas are necessary in the field of psychiatric research. One such new development is epigenetics, a branch of molecular biology investigating factors that orchestrate activities of the genome. Epigenetic research indicates that regulation of gene activity is critically important for normal functioning of the genome. Even genes that have no mutations or disease-predisposing DNA polymorphisms may be useless or even harmful if not expressed in the appropriate amount, at the right time of the cell cycle, or in the right compartment of the nucleus. The epigenetics research program may significantly contribute to our understanding of the molecular basis of mental diseases and addictions, and lead to the development of new diagnostic approaches and individualized treatment. Our CAMH epigenetics group have performed a comprehensive re-analysis of the main etiological theories of schizophrenia and bipolar disorder, and concluded that the epigenetic paradigm is able to unify, under the epigenetic "umbrella", a wide variety of biological and psychological theories as well as empirical findings that pertain to major psychosis. The epigenetic theory does not reject the role of DNA sequence variation but rather suggests that in complex diseases contribution of epigenetic factors may be substantial, and DNA sequence variation within genes should be investigated in parallel with epigenetic regulation of genes. Epigenetics may become the 'master key' to numerous 'locks' of major psychosis and other psychiatric disorders. Our research projects are dedicated to a detailed epigenetic analysis of the genome in schizophrenia, bipolar disorder and other complex disorders. In collaboration with several academic and corporate research groups, we developed a detailed high-throughput microarray-based method of profiling of DNA modification on a genome-wide scale. Since there are no sites in the brain that are specifically affected in major psychosis, the regions exhibiting the most consistent neuropathological changes (prefrontal and temporal cortex, including hippocampus) are the primary targets of our epigenetic studies. Epigenetics can be thought of as a "third wave" in psychiatric research, the first two being traditional genetic and environmental
studies. A significant advantage of the epigenetic theory is that it can unify a wide variety of biological and psychological
theories as well as empirical findings that pertain to major psychosis under the epigenetic "umbrella".
RESEARCH (Ongoing projects)
07/2005 - 06/2010 Molecular Epigenetic Studies of Major Depression. National Institute of Mental Health (NIMH). 09/2002 – 08/2006 Epigenetic studies of chr 22 in major psychosis. Ontario Mental Health Foundation (OMHF) 10/2005- 09/2008 Epigenetic studies of schizophrenia. Canadian Institutes of Health Research (CIHR) 09/2005-08/2007 Epigenomic profiles of major psychiatric disease: the first 15% of the genome. National Alliance for Research on Schizophrenia and Depression (NARSAD). 08/2003 – 07/2006 Epigenetic studies of chromosome 22 in major psychosis. National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD), and Ontario Mental Health Foundation (OMHF) 06/2005-05/2007 Microarray- based epigenetic study of the human insulin gene. Canadian Diabetes Association (CDA) 03/2006-02/2007 Molecular Basis of Bilateral Breast cancer. Canadian Cancer Etiology Research Network (CCERN) 08/2004-07/2006 Epigenetics of retroelements in major psychosis. Stanley Foundation
PUBLICATIONS (Last 5 years)
Petronis A. Human morbid genetics revisited: relevance of epigenetics. Trends in Genetics, 17 (3): 142-146; 2001. Basile VS, Ozdemir V, Masellis M, Meltzer HY, Lieberman JA, Potkin SG, Macciardi F, Petronis A, Kennedy JL. Lack of association between serotonin 2A receptor gene (HTR2A) and tardive dyskinesia in schizophrenia. Molec. Psychiatry, 6: 230-234; 2001. Petronis A. Epigenetics: Influence on Behavioral Disorders. Encyclopedia of the Human Genome. Nature Publishing Group; 2003. Petronis A, Popendikyte V, Kan PX, Sasaki T. Major psychosis and chromosome 22: genetics meets epigenetics. CNS Spectrums; 7(3): 209-214; 2002 Muglia P, Petronis A, Mundo E, Lander S, Cate T, Kennedy JL. Dopamine D4 receptor and tyrosine hydroxylase genes in bipolar disorder: evidence for a role of DRD4. Molecular Psychiatry; 7(8):860-6; 2002 Kato C, Okazaki Y, Petronis A, Sasaki T. Molecular genetic studies of schizophrenia: challenges and insights. Neuroscience Research 43(4):295-304; 2002 Petronis A, Gottesman II, Kan PX, Kennedy JL, Basile VS, Paterson AD, Popendikyte V. Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance? Schizophrenia Bulletin, 29(1): 169-178; 2003 Petronis A. Epigenetics and bipolar disorders: new opportunities and challenges. American Journal of Medical Genetics (Seminars Series),123C(1):65-75; 2003 Petronis A. The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis. Biological Psychiatry 55(10): 965-70; 2004. Kan PX, Popendikyte V, Kaminsky ZA, Yolken RH, and Petronis A. Epigenetic studies of genomic retroelements in major psychosis. Schizophrenia Research 67: 95-106; 2004. Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, and Jinno Y. Age related changes of the 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Annals of Human Genetics 68(Pt 3): 196-204; 2004. Sivagnanasundaram S, Broman KW, Liu M, Petronis A. Quasi-linkage: a confounding factor in linkage analysis of complex diseases? Human Genetics 114(6): 588-93; 2004. Petronis A.Neurodevelopment, schizophrenia, and epigenetics. In: Neurodevelopment and Schizophrenia. Eds: M. Keshavan, J.L. Kennedy, Murray R. Oxford University Press, 174-190; 2004. Flanagan J,Petronis A. Pharmacoepigenetics: from the basic mechanisms to therapeutic applications. In: Pharmacogenomics: Second Edition, Revised and Expanded. Eds: W. Kalow, U.A. Meyer, R. Tyndale. Marcel Dekker, Inc. New York NY. 461-489; 2005 Wong AH, Gottesman II, Petronis A. Phenotypic differences in genetically identical organisms: the epigenetic perspective. Human Molecular Genetics 14 Suppl 1:R11-8; 2005. Kaminsky ZA, Popendikyte V, Assadzadeh A, and Petronis A. Search for somatic DNA variation in the brain: investigation of the serotonin 2A receptor gene. Mammalian Genome, 16(8):587-93; 2005. Kaminsky ZA, Assadzadeh A, Flanagan J, and Petronis A. Single Nucleotide Extension Technology for Quantitative Site Specific Evaluation of metC/C in GC-Rich Regions. Nucleic Acid Research, 33(10): e95; 2005. Schumacher A, Kapranov P, Kaminsky ZA, Flanagan J, Assadzadeh A, Yau P, Virtanen C, Winegarden N, Cheng J, Gingeras T, Petronis A. Microarray-based DNA Methylation Profiling: Technology and Applications. Nucleic Acid Research, 34(2):528-42; 2006. Schumacher A, Petronis A. Epigenetics of Complex Disease: from the General Theory to Laboratory Experiment. Current Methods in Microbiology and Immunology, 2006, in press. Petronis A. Epigenetics and Twins: Three Variations on the Theme. Trends in Genetics, 2006, in press. Flanagan J, Popendikyte V, Pozdniakovaite N, Sobolev M, Assadzadeh A, Schumacher A, Zangeneh M, Lau L, Virtanen C, Wang S-C, and Petronis A. Intra- and Inter- Individual Epigenetic Variation in Human Germ Cells. American Journal of Human Genetics, 2006 in, press.
SCIENCE WRITERS WRITE ABOUT US
Same Difference: Twins' gene regulation isn't identical. Science News Week of July 9, 2005; Vol. 168, No. 2 , p. 19 How epigenetics affects twins. How epigenetics affects twins. 8 July 2005. Genome Biology. http://genomebiology.com/researchnews/default.asp?arx_id=gb-spotlight-20050708-02 A Pregnant Mother's Diet May Turn the Genes Around. The New York Times. October 7, 2003. http://people.ccmr.cornell.edu/~ginsparg/Phys446-546/fa03/nyt07oct03epi.html
Epigenetics: The Science Of Change. Environmental Health Perspectives Volume 114, Number 3, March 2006
Code 2. The Globe and Mail. March 11, 2006. http://72.14.205.104/search?q=cache:w_JD2meHw4IJ:www.workopolis.com/servlet/Content/fasttrack/20060311/CODE11%3Fsection%3DHealthcare+petronis+arturas&hl=en&ct=clnk&cd=40
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Last updated: Jul 25, 2006 9:24 AM Published: May 17, 2007 6:22 PM ID#P18232 |