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In our lab, we ascertain the mechanisms (gene expression, epigenetically regulated) by which prenatal and parental and maternal and paternal preconception insults induce neurobehavioral birth defects in mouse and chick model and their reversal by adult stem cell therapy and by manipulating the regulating system. Ascertaining the mechanisms by which our reversal agents exert their therapeutic action provides the groundwork for future studies on reversal of preconception-induced neurobehavioral teratogenicity toward clinical application.
Further developing chick and mouse models for studying the effect of parental preconception exposure to neuroteratogens on the offspring’s neurobehavioral development (neurobehavioral teratology models).
Assessment of pertinent alterations of gene expression in the offspring (nearly hatching chick embryos and mice offspring) which are mediated by parental neuroteratogen exposure. For example, cholinergic (CHRM1, CHRM2, SLC18A3 and the mechanistically related, PKCß), serotonergic (SLC6A4), neurogenesis (BDNF, DCX) and the early gene FOS.
Investigating the potentially involved epigenetic mechanisms mediating the transfer of deleterious effects to the offspring after paternal neuroteratogen exposure. This includes investigating alterations in genes involved in DNA methylation (MBD2, MBD3 and MeCP2), histone modification (SETDB1 and SETDB2), microRNA regulation (miR-29a, miR-6612 and miR-221) and other potentially involved “epigenetic” genes (CREB and REST).
Reversal of the molecular alterations induced by parental exposure to insults with a. stem cell transplantation b. epigenetic manipulations (e.g., RNA mimics/antisense oligonucleotides.)
Chick mesenchymal stem cell culture for transplantation into the chick embryo’s brain
Rimawi, I. A. Ornoy and J. Yanai. Paternal and/or maternal preconception-induced neurobehavioral teratogenicity in animal and human models. Research Bulletin 174: 103–121 (2021).
This review discusses old and recent findings in animal and human models on neurobehavioral teratological consequences of various insults induced during maternal preconception and paternal exposure. The Accumulating findings suggest that many of these insults produce long-lasting, often robust, consequences. In a few studies, the findings extend across more than one generation, as is mentioned in the specific studies and in the summary table. Previously associated mechanisms and new suggested mechanisms are being presented. Preliminary understanding of these mechanisms enabled initial research on the prevention and even reversal of the various deficits induced by parental exposure to insults. A review and discussion of these mechanisms is another major leap of the present review.
Yanai, J., M. Vigoda, and A. Ornoy Reversal of Neurobehavioral Teratogenicity in animal models and human: Three Decades of Progress. Brain Research Bulletin 150: 328–342 (2019).
This review intends to present the development of the field of neurobehavioral teratogenicity since the pioneer studies in the 80’s and raises the central issues related to reversal/alleviation of neuroteratogenicity.
Pinkas A., G. Turgeman, S. Tayeb and J. Yanai. An avian model for ascertaining the mechanisms of organophosphate neuroteratogenicity and its therapy with mesenchymal stem cell transplantation. Neurotoxicology and teratology 50: 73-81(2015).
A fast and simple model which uses animals lower on the evolutionary scale is beneficial for progress in neuroteratological research. Here, we established this novel model and applied it in the study of the detrimental effects of pre-hatch exposure to chlorpyrifos on neurogenesis and several neurotransmitter systems in the chick and their reversal, using mesenchymal stem cell (MSC) transplantation.
Ben-Shaanan T. L., T. Ben-Hur, and J. Yanai. Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain. Molecular Psychiatry, 13: 222-231 (2008).
This study suggests one mechanism for the therapeutic action of transplanted neural progenitors, the enhancement of the production of endogenous cells, pointing to future clinical applications in this direction by use of neural progenitors or by analogous cell-inducing techniques.
Yanai, J. and G.E. McClearn. Assortative mating in mice and the incest taboo. Nature 238:281-282 (1972).
PhD student
Parental chlorpyrifos exposure effects on the offspring, involved mechanisms and methods of reversal.
98501 Neurobehavioral Birth Defects: Mechanisms and Reversal
אנטומיה של האדם, אחראי על פרק הגפיים – 75210
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1972 – Ph.D. Univ. of Colorado.
1978 – Present, Lecturer, Senior Lecturer; Associate Professor; Professor.
1991 – 2020, Professor (Adjunct); Department of Pharmacology, Duke University Medical School, Durham, North Carolina, USA