New York Medical College

Libor Velíšek, MD, PhD
Professor of Cell Biology & Anatomy, and Pediatrics
Director, MD-PhD program
Director, Behavioral Phenotyping Core Facility

Libor Velíšek, MD, PhD

 

Email:

Libor_Velisek@nymc.edu

Address:

Department of Cell Biology & Anatomy
Basic Sciences Building, Room A20
Valhalla, NY 10595

 

 

Professional Interests:

For 15 years my lab has been engaged in work across the range of problems associated with research in developmental epilepsy including (1) developing and validation of a model of infantile spasms, a devastating seizure syndrome of infancy with specific features and therapies, and catastrophic consequences; (2) molecular mechanisms of prenatal corticosteroid exposure in the postnatal seizure susceptibility and behavioral outcome and its relevance for autistic behaviors; and, (3) mechanisms and models of idiopathic generalized epilepsy/juvenile myoclonic epilepsy. We were the first to develop and validate a viable model of infantile spasms that can be used for testing of new treatment approaches. This model stems from our previous work investigating the effects and mechanisms of prenatal exposure to synthetic corticosteroids. We noted that prenatal exposure to synthetic corticosteroids on top of postnatal behavioral changes also alters postnatal levels of cortisol and ACTH in experimental animals reproducing thus findings in patients with infantile spasms. In the model, prenatal priming with synthetic corticosteroids provides a background for postnatal development of spasms after a trigger with NMDA during developmentally specific period. Resulting flexion spasms with semiology similar to human spasms have similar electrographic features, and do respond to the principal therapy of infantile spasms, i.e., ACTH. Our most recent work identified that prenatal stress has similar effects as prenatal exposure to synthetic corticosteroids in terms of priming the brain for postnatal expression of changes. We were also able to determine that additional melanocortin-derived peptides (besides ACTH) may be the powerful tools in treatment of infantile spasms. We also study mouse model of idiopathic generalized epilepsy using mice hemizygous for Brd2, a prominent gene associated with idiopathic generalized epilepsy in humans. We have determined that one of the culprits for the occurrence of spontaneous seizures in these mice may be downregulation of inhibitory neurotransmitter GABA along the basal ganglia pathway.

The model of infantile spasms gives us a unique opportunity to study by extracellular and intracellular electrophysiology as well as molecular biology techniques the pathogenetic features of these spasms. Using in vivo metabolic imaging, we identified several brain nuclei intimately involved in development of spasms. We will study neuronal physiology in these nuclei, as well its changes preceding the development of spasms. For this purpose, we will use a simplified synaptic system of brain slices from these critical structures in vitro and whole cell patch clamp approach. Because the prenatal exposure to synthetic corticosteroids is a significant prerequisite of the infantile spasms model and prenatal corticosteroids have multiple effects on DNA transcription, we will use molecular biology techniques including siRNA blockade and DNA power sequencing to determine, which of those genomic changes are significant for the development and expression of spasms.

Finally, we have established a Behavioral Phenotyping Core Facility for mice and rats to determine changes in behavioral phenotypes based on the genome, action of drugs, or environmental changes. The facility is available to NYMC investigators.

Education Profile:

Graduate Degree:   M.D., Ph.D.

Graduate Degree Institution:   Faculty of General Medicine of the Charles University, Prague, Czechoslovakia, 1984 (M.D.), Human Physiology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia, 1989 (Ph.D.)

Selected Bibliography:

 

Search PubMed for publications of Libor Velisek

 

 

 

 

 

 

 

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