Post Doctoral Fellows
2001-2007, Post-Doctoral Fellow, Harvard University, Psychiatry, Epidemiology, Genetics, Epigenetics
1975-1985, Iran National University, Iran University of Medical Sciences, General Medicing, Psychiatry
I have been working as a faculty member in the department of psychiatry at Iran University of Medical Sciences for 15 years. During this time I was involved in the teaching of residents and medical students in a clinical setting and teaching of Medical Doctors and Psychiatrist in Continuing Medical Education Courses in the area of Clinical Psychiatry, Psychiatric Epidemiology, Diagnostic Classification, Psychiatric Genetics and Epigenetics, Psychopharmacology, Alcohol and Drug Abuse, Neuropsychiatry and Neurodevelopment, Co-morbidity in Psychiatric Disorders and PTSD.
My experience as a clinical psychiatrist and research in the field of neuroscience led me to realize that little is known about the etiology of major mental disorders. I recognized that the only way to improve the treatment strategies for these devastating diseases is to use novel insights from basic bench research. Thus, I decided to look for opportunities to conduct cutting edge research in psychiatry. This search resulted in my enrollment in a post-doctoral Psychiatric Genetics Training Program at the Harvard Institute of Psychiatric Epidemiology and Genetics beginning November, 2001. Under the guidance of Dr. Ming Tsuang, an outstanding clinician scientist in Psychiatry at the Harvard University and Dr. Sam Thiagaligam, an expert molecular geneticist at the Boston University, I was working on the mechanisms of genes-environment interactions in brain development and the role of environment insults in the pathogenesis of mental diseases.
This unique collaboration enabled me to combine the expertise of these mentors to take a novel approach to dissect the molecular basis of the psychiatric symptoms that are influenced by the environmental effects based on alterations in genes promoter DNA methylation. Since January 2003, I have been involved in laboratory experiments on the epigenetic modulation of several gene promoter regions using more than 120 post-mortem human brains affected with schizophrenia and bipolar disorder. During the last six years, was able to pursue research in psychiatric epigenetics, written three review articles on “methylomics in psychiatry”, and published three articles on my original research findings. As a psychiatrist with skills in basic science research, my ultimate goal is to find novel strategies to treat the affected patients based on their genetic and epigenetic make up and potentially develop new therapeutic modalities for these diseases.
Abdolmaleky HM, Faraone SV, Glatt SJ and Tsuang MT. Meta-analysis of Association Between the T102C Polymorphism of the 5HT2a Receptor Gene and Schizophrenia. Schizo Res, 2004:1;67(1):53-62.
Abdolmaleky HM, Smith CL, Faraone SV, Shafa R, Stone WS, Glatt SJ, Tsuang MT. Methylomics in psychiatry: Modulation of gene-environment interactions may be through DNA methylation. Am J Med Genet.2004:15;127B(1):51-9
Abdolmaleky HM, Cheng KH, Russo A, Smith CL, Faraone SV, Wilcox M, Shafa R, Glatt SJ, Nguyen G, Ponte JF, Thiagalingam S, Tsuang MT. Hypermethylation of the Reelin (RELN) Promoter in the Brain of Schizophrenic Patients: A Preliminary Report. Am J Med Genet B Neuropsychiatr Genet. 2005;
Abdolmaleky HM, Thiagalingam S, Wilcox M. Genetics and Epigenetics in Major Mental Disorders: Dilemmas, Achievements, Applications and Future Scope. Am J Pharmacogenomics. 2005;5(3):149-60.
Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, Shafa R, Aleali B, Carnevale J, Pan H, Papageorgis P, Ponte JF, Sivaraman V, Tsuang MT, Thiagalingam S. Hypomethylation of MB-COMT Promoter is a Major Risk Factor for Schizophrenia and Bipolar Disorder, Hum Mol Genet. 2006
Abdolmaleky HM, Zhou, RJ., Thiagalingam S and Smith CL. Epigenetic and Pharmacoepigenomic Studies of Major Psychoses and Potentials for Therapeutics, Pharmacogenomics. 2008 Dec;9(12):1809-23.
Abdolmaleky HM, Smith CL, Zhou, RJ., Thiagalingam S. “Epigenetic Alterations of Dopaminergic System in Major Psychiatric Disorders” in “Pharmacogenomics in Drug Discovery and Development”. Editor: Yan Q, Humana Press, 2008
Abdolmaleky HM, Smith CL, Zhou, RJ. Thiagalingam S “Epigenetic modulation of reelin function in schizophrenia and bipolar disorders” in “Reelin Glycoprotein, biology, structure and roles in health and disease” Editor: Fatemi SH, Springer, 2008
Postdoctoral Associate, Biomedical Genetics, Boston University School of Medicine
Ph.D., Tufts University, USA (2014)
Master of Science, Tufts University, USA (2010)
Master of Medicine, Fudan University, China (2008)
MD., Fudan University, China (2005)
I have research experience in the fields of gene-by-environment interactions, epigenetics, genetic epidemiology, nutritional genetics & genomics, biostatistics/statistics, and public health. I have particular research interest in the interactions between genetics, epigenetics, and environmental factors. I have found that epigenetics, especially DNA methylation, is regulated by the haplotypes of genetic variants on a genome-wide scale. My researches further suggested that DNA methylation contribute partially to the observed gene-by-environment interactions. For example, at the APOE locus, I found that one promoter single nucleotide polymorphism (SNP) interacted with the age to modulate APOE methylation. Also, I have shown that the DNA methylation mechanism may, in part, explain the observed interactions between omega-3 polyunsaturated fatty acids and genetic variants to modulate blood lipids and inflammation markers.
I do believe that most diseases are contributed by both genetics and epigenetics. Genetics determines whether an individual is susceptible to the disease while epigenetics controls when and how the individual will develop the disease. Currently, I am testing this hypothesis in Alzheimer disease (AD), one of the major diseases showing extremely intimate relationships with both genetics and epigenetics.
My research focus on one particular type of SNPs, CpG related SNPs (CGSs). CGSs are defined as those SNPs which can change the formation of CpG dinucleotides. Each CGS has two types of alleles which can either create or disrupt CpG dinucleotides. CpGs are the primary target sites for DNA methylation. CGSs account for a significant fraction (38% ~ 88%) of allele specific methylation regions in the human genome. Also, over 80% CGSs were shown to have a regulatory role in DNA methylation. Recently, we found that the haplotype of multiple CGSs are associated with DNA methylation patterns on a genome-wide scale. CGSs may be related to AD because both AD and DNA methylation are associated with aging. DNA methylation patterns were reported to be associated with multiple age-related diseases such as AD, age-related macular degeneration (AMD), and atherosclerosis. Also, the two SNPs whose allelic combinations encode the common APOE isoforms are CpG related SNPs (CGSs), and the number of CpG sites on the two chromatids is genotype dependent. For example, ε2/ε2, ε3/ε3, and ε4/ε4 homozygotes have 0, 1 and 2 CpG sites, respectively. Furthermore, we have shown that APOE methylations were high, medium, and low for the ε4 carriers, ε3/ ε3 homozygotes, and ε2 carriers, respectively. Focusing on methylation-related SNPs will increase the power to detect putatively functionally-relevant variants that are often overlooked in standard GWAS and deep sequencing studies. Also, this study may help us identify and better understand the AD-associated variants not in or near genes, possibly through their potential effects on gene transcription.
1. Ma Y., Tucker KL., Smith CE., Lee YC., Huang T., Richardson K., Parnell LD., Lai CQ., Young KL., Justice AE., Shao Y., North KE., Ordovas JM. Lipoprotein lipase variants interact with polyunsaturated fatty acids for obesity traits in women: replication in two populations. Nutrition, Metabolism & Cardiovascular Disease., 2014, PubMed PMID: 25156894.
2. Ma Y., Smith CE., Lai CQ., Irvin MR., Parnell LD., Lee YC., Pham L., Aslibekyan S., Claas SA., Tsai M., Borecki IB., Kabagambe EK., Berciano S., Ordovas JM. and Absher D. and Arnett DK. Genetic variants modulate the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study. Aging Cell, 2014. PubMed PMID: 25476875.
3. Ma Y., Guo H. Determination of deoxynivalenol in grains and beans by capillary gas chromatography. Chinese J. Health Lab. Tech., May. 2007; 5(17): 789-790.
4. Ma Y., Guo H. Mini-review of studies on the carcinogenicity of deoxynivalenol. Environ. Toxicol. Pharmacol. 2008 Jan. PubMed PMID: 21783829.
5. Zheng JS, Arnett DK, Parnell LD, Lee YC, Ma Y, Smith CE, Richardson K, Li D, Borecki IB, Ordovas JM, Tucker KL, Lai CQ. Genetic Variants at PSMD3 Interact with Dietary Fat and Carbohydrate to Modulate Insulin Resistance. J. Nutr. 2013 Jan. PubMed PMID: 23303871.
6. Zheng JS, Arnett DK, Parnell LD, Lee YC, Ma Y, Smith CE, Richardson K, Li D, Borecki IB, Tucker KL, Ordovas JM, Lai CQ. Polyunsaturated fatty acids modulate the association between PIK3CA-KCNMB3 genetic variants and insulin resistance. Plos One, 2013 Jun. PubMed PMID: 23826284.
7. Parnell LD, Blokker BA, Dashti HS, Nesbeth PD, Cooper BE, Ma Y, Lee YC, Hou R, Lai CQ, Richardson K, Ordovas JM, CardioG×E, a catalog of gene-environment interactions for cardiometabolic traits. BioData Mining, 2014. PubMed PMID: 25368670.
8. Smith CE, Follis JL, Nettleton JA, Foy M, Wu JHY, Ma Y, et al., Dietary fatty acids interactions with genetic variants for plasma and erythrocyte fatty acids: meta-analysis of 9 studies in the CHARGE consortium. 2014. Molecular Nutrition and Food Research. 2015 Jan. PubMed PMID: 25626431.
9. Ma Y., Smith CE., Lai CQ., Irvin MR., Parnell L.D., Lee YC., Pham L., Aslibekyan S., Class SA., Tsai M., Borecki IB., Kabagambe EK., Ordovas JM. and Arnett DK. The effects of omega-3 fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter. Mol.Nutr. & Food Res. 2015. In press.
1. Ma Y., Smith CE., Lee YC., Parnell LD., Lai CQ., Ordovas JM. Haplotypes of CpG-related SNPs and associations with DNA methylation patterns. Book: Genome-Wide Association Studies: From Polymorphism to Personalized Medicine, Chapter 27., 2015. Cambridge University Press.
2. Lai CQ., Ma Y., Parnell LD., Genetics and gene-environment interactions on longevity and lifespan. Book: Gene-Environment Interactions and its Role in Human Health and Disease, 2015. Nova Science Publishers.