The focus of the laboratory is to identify epigenetic factors underlying psychiatric disease with a particular focus on mood disorders. We employ genome wide exploratory analyses using microarrays to identify disease associated epigenetic variation. Our current focus is on major depression, postpartum depression, and suicide. We also study animal models of psychiatric conditions side by side with human studies in attempts to better understand the molecular epigenetic underpinnings of psychiatric phenotypes and to enable the generation of true “bench to bedside” translational findings. The laboratory activities are divided between the development of novel methods and bioinformatic tools to aid in the study of epigenetics and basic disease and translational research.
A recent focus in the laboratory has been to generate a method to address cellular heterogeneity confounds in brain derived epigenomic datasets. We have recently generated a bioinformatic method in an R package called CETS that is capable of quantifying and normalizing for cellular heterogeneity based on DNA methylation proxies of neuronal and glial densities. We have also generated an analysis program called BioTile designed for the identification of differentially methylated regions in tiling microarray data, which is well suited to identifying small and relatively short DNA methylation changes such as those that might be expected to be found in epigenomic studies of the brain. It is our hope that these tools will better enable the identification of robust epigenetic changes important for the etiology of psychiatric phenotypes.
An additional focus of the lab is the development of disease risk predictive biomarkers utilizing DNA methylation marks in peripheral tissues. We are currently in the process of developing biomarkers predictive of postpartum depression and suicide risk.
Guintivano J, Arad M, Gould TD, Payne JL, Kaminsky ZA. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Molecular Psychiatry 2013; 2013/05/22 edn2013. PMID: 23689534
Guintivano J, Arad M, Tamashiro KL, Gould TD, Kaminsky ZA. BioTile, A Perl based tool for the identification of differentially enriched regions in tiling microarray data. BMC Bioinformatics 2013; 14: 76. PMID: 23452827
Guintivano J, Aryee M, Kaminsky Z.. A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. Epigenetics.. 2013 Feb 20;8(3). PMID: 23426267.
Zachary Kaminsky, Mamoru Tochigi., Peixin Jia, Jonathan Mill, Andrew Kwan, Francine Benes, Ilya Ioshikhes, John Vincent, James Kennedy, John Strauss, Shraddha Pai, Sun-Chong Wang, Arturas Petronis. A multi-tissue analysis identifies HCG9 methylation differences in bipolar disorder. Molecular Psychiatry. 2011; PMID: 21647149
Zachary A. Kaminsky, Thomas Tang., Sun-Chong Wang, Carolyn Ptak, Gabriel H.T. Oh, Albert H.C.Wong, Laura A. Feldcamp, Carl Virtanen, Jonas Halfvarson, Curt Tysk, Allan F. McRae, Peter M.Visscher, Grant W. Montgomery, Irving I. Gottesman, Nicholas G. Martin, Art Petronis. DNA Methylation Profiles in Monozygotic and Dizygotic Twins. Nature Genetics.2009; 41(2):240-5. PMID: 19151718
Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., Jia, P., Assadzadeh, A., Flanagan, J., Schumacher, A., Wang, S.C. & Petronis, A. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. American Journal of Human Genetic. 2008; 82; 696-711. PMID:18319075
Schumacher A, Kapranov P, Kaminsky Z.A., et al. Microarray-based DNA methylation profiling: technology and applications. Nucleic Acids Research. 2006; 34: 528-42. PMID: 16428248
Kaminsky, Z., Petronis, A., Wang, S.C., Levine, B., Ghaffar, O., Floden, D. & Feinstein, A. Epigenetics of personality traits: an illustrative study of identical twins discordant for risk-taking behavior. Twin Research and Human Genetic. 2008: 11: 1-11. PMID: 18251670
Kaminsky, Z, The Role of Epigenomics in Genetically Identical Individuals, Omics in Neurology and Neuronscience. Oxford University Press, in press.
Rene Cortese, Andrew Kwan, Emilie Lalonde, Olga Bryzgunova, Anna Bondar, Ying Wu, Juozas Gordevicius, Mina Park, Gabriel Oh, Zachary Kaminsky, Justina Tverkuviene, Arvydas Laurinavicius, Feliksas Jankevicius, Dorota H.S. Sendorek, Syed Haider, Sun-Chong Wang, Sonata Jarmalaite, Pavel Laktionov, Paul C. Boutros and Arturas Petronis. Epigenetic markers of prostate cancer in plasma circulating DNA, Human Molecular Genetics. In press.
Kaminsky, Z., Wang, S-C., Petronis, A. Complex disease, gender and epigenetics. Annals of Medicine. 2006; 38, 530 - 544. PMID: 17438668
Mill, J., Yazdanpanah, S., Gucke,l. E., Ziegler, S., Kaminsky, Z., Petronis, A.. Whole genome amplification of sodium bisulfite-treated DNA allows the accurate estimate of methylated cytosine density in limited DNA resources. Biotechniques.2006; 41: 603-7. PMID: 17140118
Kaminsky, Z. A., Popendikyte, V., Assadzadeh, A. and Petronis, A. Search for somatic DNA variation in the brain: investigation of the serotonin 2A receptor gene. Mammalian Genome. 2005; 16: 587-93.
Kaminsky, Z. A., Assadzadeh, A., Flanagan, J. and Petronis, A. Single nucleotide extension technology for quantitative site-specific evaluation of metC/C in GC-rich regions. Nucleic Acids Research.2005; 33: e95. PMID: 16180140
Kan, P. X., Popendikyte, V., Kaminsky, Z. A., Yolken, R. H. and Petronis, A. Epigenetic studies of genomic retroelements in major psychosis. Schizophrenia Research.2004; 67: 95-106. PMID: 14741329
Zachary Kaminsky, Ph.D.
Johns Hopkins University School of Medicine
Department of Psychiatry and Behavioral Sciences
720 Rutland Avenue
Ross Research Building 1070
Baltimore, MD, 21205