Associate Scientist, Division of Genetics & Development, Children's Health Research Institute
Assistant Professor, Departments of Physiology & Pharmacology and Biology, Western University
How does my research help children?
Intellectual Disability (ID) is defined by limitations in intellectual functioning and adaptive behaviour beginning before the age of 18 (www.aaidd.org). ID affects thousands of Canadian children (~1% of the global population). My research aims to understand the genetic and molecular mechanisms underlying ID. Understanding the genetic causes of ID can lead to improved diagnostics and provides insight into the molecular mechanisms that are disrupted in the brain. Further investigation into these mechanisms is an essential step towards developing therapies.
The main goals of the Kramer lab are to understand the role of epigenetics in learning and memory, and to understand the contribution of epigenetic deregulation to human cognitive disorders, such as Intellectual Disability (ID) and autism.
Epigenetics is the study of long lasting changes in gene expression that are regulated independent of the underlying DNA sequence. Epigenetics was first discussed in the context of development and was proposed to be the mechanism that allows for cellular differentiation by determining the "correct" gene expression profile for a given cell type. Epigenetic modifications were traditionally defined as stable and heritable; however, recent studies have shown that they can be highly dynamic, especially in neurons. This dynamic regulation of chromatin structure in the brain is thought to be essential for processes like memory and addiction.
My research is focused on epigenetic regulatory complexes involved in histone modification (acetylation/methylation) and ATP-dependent chromatin remodelling (SWI/SNF superfamily). I use a systems-biology approach to study these protein complexes, combining high-throughput learning and memory assays and large-scale sub-brain genomics in the fruit fly, Drosophila melanogaster. In addition, I aim to further understand the genetic contribution of epigenetic regulators to ID and improve molecular diagnostics for ID.
Epigenetics in Intellectual Disability
Berube NG and Kramer JM
In Epigenetics in Psychiatry (eds. Jacob Peedicayil, Dimitri Avramopoulos, and Dennis R. Grayson). 2014; In Press, Elsevier
The genetics of cognitive epigenetics
Kleefstra T, Schenck A. Kramer JM, van Bokhoven H
Neuropharmacology. 2014; 80:83-94
Ubiquitin ligase HUWE1 regulates axon branching through the Wnt/beta-catenin pathway in a Drosophila model for intellectual disability
Vandewalle J, Langen M, Zschaetzsch M, Nijhof B, Kramer JM, Brems H, Bauters M, Lauwers E, Srahna M, Marynen P, Verstreken P, Schenck A, Hassan BA, Froyen G
PLoS One. 2013; 8(11):e81791
Restoration of polyamines protects from age-induced memory impairment in an autophagy-dependent manner
Gupta VK, Scheunemann L, Eisenberg T, Mertel S, Bhukel A, Koemans TS, Kramer JM, Liu KS, Schroeder S, Stunnenberg HG, Sinner F, Magnes C, Pieber TR, Dipt S, Fiala A, Schenck A, Schwaerzel M, Madeo F, Sigrist SJ
Nature Neuroscience. 2013; 16(10):1453-60
CEP89 is required for mitochondrial metabolism and neuronal function in man and fly
van Bon BWM, Oortveld MAW, Nijtmans LG, Fenckova M, Nijhof B, Besseling J, Kramer JM, de Leeuw N, Castells Nobau A, Asztalos L, Viragh E, Ruiter M, Hofmann F, Eshuis L, Collavin L, Huynen MA, Asztalos Z, Verstreken P, Rodenburg RJ, Smeitink JA, de Vries BBA, Schenck A
Human Molecular Genetics. 2013; 22(15):3138-51
Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders
Iqbal Z, Vandeweyer G, van der Voet M, Waryah AM, Zahoor MY, Besseling J, Tomas Roca L, Vulto-van Silfhout AT, Nijhof B, Kramer JM, van der Aa N, Ansar M, Peeters H, Helsmoortel C, Gilissen C, Vissers L, Veltman JA, de Brouwer AMP, Kooy FR, Riazuddin S, Schenck A, van Bokhoven H, Rooms L
Human Molecular Genetics. 2013; 22(10):1960-70
Epigenetic regulation of memory: implications in human cognitive disorders
Biomolecular Concepts. 2013; 4(1):1-12
Disruption of an EHMT1-associated chromatin modification module causes intellectual disability
Kleefstra T*, Kramer JM*, Neveling K, Willemsen MH, Koemans T, Vissers LE, Wissink-Lindhout W, van den Akker W, Kasri NN, Nillesen WM, Prescott T, Clark RD, Devriendt K, van Reeuwijk J, de Brouwer APM, Gilissen C, Zhou H, Veltman JA, Schenck A, van Bokhoven H
American Journal of Human Genetics. 2012; 91(1):73-82 (*equal contribution)
Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome
Koolen DA*, Kramer JM*, Neveling K*, Nillessen WM, Moore-Barton H, Elmslie FV, Toutain A, Amiel J, Tsai AC, Cheung SW, Gillissen C, Verwiel E, Martens S, Feuth T, Bongers E, de Vries P, Scheffers H, Vissers LE, de Brouwer APM, Brunner HG, Schenck A, Veltman JA, Yntema H, de Vries BAB
Nature Genetics. 2012; 44(6):639-41 (*equal contribution )
Epigenetic regulation of learning & memory by Drosophila EHMT/G9a
Kramer JM, Kochinke K, Oortveld MAW, Marks H, Kramer D, de Jong EK, Asztalos Z, Westwood JT, Stunnenberg HG, Sokolowski MB, Keleman K, Zhou H, van Bokhoven H, Schenck A
PLoS Biology. 2011; 9(1):e1000569
Phone: 519-661-2111, x83740
Email: jkramer6 [at] uwo [dot] ca
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