Advisory Board

Professor Moshe Szyf

The PhysOrg article Childhood trauma has life-long effect on genes and the brain said

McGill University and Douglas Institute scientists have discovered that childhood trauma can actually alter your DNA and shape the way your genes work. This confirms in humans earlier findings in rats, that maternal care plays a significant role in influencing the genes that control our stress response.
 
Using a sample of 36 brains; 12 suicide victims who were abused; 12 suicide victims who were not abused and 12 controls, the researchers discovered different epigenetic markings in the brains of the abused group. These markings influence the hypothalamic-pituitary-adrenal (HPA) function, a stress-response which increases the risk of suicide.
 
This research builds upon findings published last May that showed how child abuse can leave epigenetic marks on DNA.
 
But, in this, the first study of its kind, Moshe Szyf, a professor in the Department of Pharmacology and Therapeutics; Gustavo Turecki, associate professor in the Department of Psychiatry who practices at the Douglas Mental Health University Institute; Michael Meaney, a professor in the Departments of Psychiatry and Neurology and Neurosurgery, who is also at the Douglas; and McGill postdoctoral research fellow Patrick McGowan have built on their world-renowned epigenetics work to uncover how parental care affects the DNA in the brains of a group of Quebec male suicide victims who suffered abuse as children.

Moshe Szyf, M.Sc., Ph.D. is Professor of Pharmacology and Therapeutics, McGill University.
 
Moshe authored DNA Methylation and Cancer Therapy, and coauthored Epigenetic programming by maternal behavior, A mammalian protein with specific demethylase activity for mCpG DNA, Maternal care as a model for experience-dependent chromatin plasticity?, DNA methylation is a reversible biological signal, Demethylase Activity Is Directed by Histone Acetylation, Inhibition of tumorigenesis by a cytosine—DNA, methyltransferase, antisense oligodeoxynucleotide, and Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life.
 
His patents include Antisense oligonucleotides having tumorigenicity-inhibiting activity, DNA methyltransferase antisense oligonucleotides, Inhibition of DNA methyltransferase, DNA demethylase, therapeutic, and diagnostic uses thereof, and Oligonucleotide inhibitors of MBD2/DNA demethylase and uses thereof.
 
His current projects include:
 
Delineating the mechanisms responsible for cell cycle regulation of DNMT1 3’UTR elements and proteins interacting with them

  • Involvement of cell cycle regulation of DNMT1 in tumorigenesis
  • Unraveling the mechanisms through which DNMT1 inhibitors block tumorigenesis
  • Methylation independent mechanisms of regulation of gene expression by DNMT1 inhibitors
  • Understanding the mechanisms through which DNMT1 regulates DNA replication

Deciphering mechanisms of active demethylation

  • Understanding the links between chromatin structure and demethylase
  • Structure function analysis of MBD2/demethylase
  • Mechanism of the demethylase reaction

Read Moshe Szyf, James McGill professor of Pharmacology and Therapeutics and New professorship for McGill Faculty of Medicine.