Marija Kundakovic

PharmD, School of Pharmacy, University of Belgrade, 2001

MSc in Experimental Pharmacology, School of Medicine, University of Belgrade, 2007

PhD in Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, 2009

Postdoc, Gene Regulation Program, Centre for Genomic Regulation, Barcelona, 2009-2010

Postdoc, Department of Psychology, Columbia University, 2010-2014

Lecturer, Department of Psychology, Columbia University, 2011-2013

Instructor, Division of Psychiatric Epigenomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 2014-2015

Epigenetic mechanisms regulate gene activity in the brain and are essential for normal brain development and control of the adult brain function. Epigenetic dysregulation has been strongly implicated in psychiatric disorders. Epigenetic modifications, such as DNA methylation and histone modifications, can be affected by both genetic and environmental risk factors and are likely mediators of molecular, structural, and functional changes in the brain involved in the initiation and maintenance of psychopathology. Dr. Kundakovic's research program integrates molecular, behavioral, structural, and computational analyses to further our understanding of epigenetic regulatory processes that shape brain and behavior with an emphasis on brain sexual dimorphism. We also study the epigenetic basis of mental disorders with an aim to help tailor novel diagnostic, preventive, and therapeutic approaches in the area of mental health.

Current and future research projects will focus on:

1. Epigenetic Mechanisms underlying Sex Differences in Brain and Behavior
   Brain structure and function are sexually dimorphic. Males and females show differences in numerous neural and behavioral phenotypes, including emotion regulation and cognitive function. Within females, behaviors also vary across the menstrual (or estrous) cycle, as fluctuating sex-hormone levels can dynamically change brain structure and function. The current lab project explores the contribution of sex hormones and epigenetic mechanisms to between- and within-sex variation in emotional behavior.
    
2. Environmental Effects on the Brain Epigenome
   Adverse environments, such as stress, toxicological exposures and malnutrition, can increase risk for psychopathology over the life course. The underlying mechanisms are just emerging and likely involve the lasting environmental effects on the brain epigenome which translate into the altered brain structure and function. A currently funded project in Dr. Kundakovic's laboratory examines the epigenetic effects of the combined early life stress and adolescent stress on the brain in the context of depression and anxiety disorders.
    
3. Development of Epigenetic Biomarkers to Predict Psychiatric Risk
   The epigenome (the collection of all epigenetic marks in a given cell) is largely cell type- and tissue-specific. However, there is increasing evidence that epigenetic signatures in peripheral tissues (e.g. blood and buccal cells) may be informative of epigenetic signatures in the brain and potentially used to diagnose and predict psychiatric disorders. In collaboration with psychiatrists and clinical psychologists, we perform epigenetic analyses of peripheral tissues of children and adolescents who are at risk for psychopathology in order to develop candidate epigenetic biomarkers for prediction of psychiatric risk.
    
4. Epigenomic Profiling in Psychiatric Disorders
   Epigenetic mechanisms have been strongly implicated in various psychiatric disorders and provide a novel candidate mechanism for intervention and treatment. Yet, the field of psychiatric epigenomics is still missing comprehensive and high-resolution studies. The future focus of the lab will be to use novel epigenomic and bioinformatic approaches to elucidate epigenetic changes associated with psychiatric disorders such as depression and schizophrenia.

Graduate and undergraduate students interested in joining my lab should contact me directly at [email protected] to discuss research and funding opportunities.

Kundakovic M. Sex-specific Epigenetics: Implications for Environmental Studies of Brain and Behavior. Curr Environ Health Rep. In Press.

Kundakovic M and Jaric I (2017). The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders. Genes 8, 104.

Kundakovic M (2017). Fearing the Mother's Virus: The Lasting Consequences of Prenatal Immune Activation on the Epigenome and Brain Function. Biol Psychiatry. 81(3):e23-e25.

Kundakovic M, Jiang Y, Kavanagh D, Dincer A, Brown L, Pothula V, Zharovsky E, Park R, Jacobov R, Magro I, Kassim B, Wiseman J, Dang K, Sieberts SK, Roussos P, Fromer M, Harris B, Lipska BK, Peters MA, Sklar P, and Akbarian S (2017). Practical Guidelines for High-resolution Epigenomic Profiling of Nucleosomal Histones in Postmortem Human Brain Tissue. Biol Psychiatry 81(2):162-170.

Peter CJ*, Fischer LK*, Kundakovic M*, Garg P*, Jakovcevski M, Dincer A, Amaral AC., Ginns EI, Galdzicka M, Bryce CP, Ratner C, Waber DP, Mokler D, Medford G, Champagne FA, Rosene DL, McGaughy JA, Sharp AJ, Galler JR, Akbarian S (2016). DNA methylation signatures of early childhood malnutrition associated with impairments in attention and cognition. Biol Psychiatry 80(10):765-774.
*equal contribution

Nestler EJ, Pena CJ, Kundakovic M, Mitchell A, and Akbarian S (2016). Epigenetic basis of mental illness. Neuroscientist 22(5):447-63.

The PsychENCODE Consortium, Akbarian S, Liu C, ..., Kundakovic M, ..., Senthil G, Lehner T, Sklar P, Sestan N (2015). The PsychENCODE Project. Nat Neurosci. 18(12):1707-1712.

Braithwaite EC, Kundakovic M, Ramchandani PG, Murphy SM, and Champagne FA (2015). Maternal prenatal depressive symptoms predict infant NRC31 1F and BDNF IV DNA methylation. Epigenetics. 10(5):408-17.

Kundakovic M, Gudsnuk K, Herbstman JB, Tang D, Perera FP, Champagne FA (2015). DNA methylation of BDNF as a biomarker of early life adversity. Proc Natl Acad Sci U S A. 112(22):6807-13.

Kundakovic M and Champagne FA (2015) Early Life Experience, Epigenetics, and the Developing Brain. Neuropsychopharmacology 40(1):141-53.

Kundakovic M (2014) Postnatal risk environments, epigenetics, and psychosis: putting the pieces together. Soc Psychiatry Psychiatr Epidemiol. 49(10):1535-6.

Kundakovic M, Lim S, Gudsnuk K, Champagne FA (2013) Sex-specific and strain-dependent effects of early life adversity on behavioral and epigenetic outcomes. Front Psychiatry 4:78.

Kundakovic M, Gudsnuk K, Franks B, Madrid J, Miller RL, Perera FP, Champagne FA (2013) Sex- specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proc Natl Acad Sci U S A 110(24): 9956-61.

Kirkbride JB, Susser E, Kundakovic M, Kresovich JK, Davey Smith G, and Relton CL (2012) Testing epigenetic factors as mediating prenatal nutritional influences on schizophrenia risk. Epigenomics 4: 303-15.

Kundakovic M and Champagne FA (2011) Epigenetic perspective on the developmental effects of bisphenol A. Brain, Behavior, and Immunity 25: 1084-93.

Grayson DR, Kundakovic M, and Sharma RP (2010) Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? Mol Pharmacol 77: 126-35.

Kundakovic M, Chen Y, Guidotti A, and Grayson DR (2009) The reelin and GAD67 promoters are activated by epigenetic drugs that facilitate the disruption of local repressor complexes. Mol Pharmacol 75: 342-54.

Guidotti A, Dong E, Kundakovic M, Satta R, Grayson DR, and Costa E (2009) Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling. Trends Pharmacol Sci 30:55-60.

Kundakovic M, Chen Y, Costa E, Grayson DRH. (2007) DNA Methyltransferase Inhibitors Coordinately Induce Expression of the Human Reelin and Glutamic Acid Decarboxylase 67 Genes. Mol Pharmacol 71: 644-53.

Grayson DR, Chen Y, Costa E, Dong E, Guidotti A, Kundakovic M, Sharma RP.H (2006) The human reelin gene: transcription factors (+), repressors (-) and the methylation switch (+/-) in schizophrenia. Pharmacol Ther 111:272-86.

Mitchell CP, Chen Y, Kundakovic M, Costa E, Grayson DRH (2005) Histone deacetylase inhibitors decrease reelin promoter methylation in vitro. J Neurochem 93:483-92.

Book Chapters

Kundakovic M (2016). Epigenetics of Psychiatric Disorders. In Tollefsbol (ed) Medical Epigenetics. Elsevier. p 335-350.

Kundakovic M, Peter C, Roussos P, and Akbarian S (2016). Epigenetic approaches towards the molecular and genetic risk architectures of schizophrenia. In Abel (ed) The Neurobiology of Schizophrenia. Elsevier. p 61-82.

Kundakovic M (2016). In utero Bisphenol A exposure and epigenetic programming of neurobehavioral outcomes. In Hollar D (ed), Epigenetics, the Environment, and Children's Health across Lifespans. Springer. p 67-92.

Kundakovic M (2014). DNA Methyltransferase Inhibitors and Psychiatric Disorders, In Peedicayil J, Avramopoulos D, and Grayson D (eds), Epigenetics in Psychiatry. Elsevier, pp 497-514.