Shelley J. Russek, Ph.D.
Professor of Pharmacology and Neuroscience
Research Interests of the Russek Laboratory
Plasticity of brain receptor systems and their importance to neurological and neuropsychiatric disease
Our chief interests surround a desire to understand how the dynamic regulation of neurotransmitter receptors in the brain shapes the development of the nervous system and how the re-establishment of developmental processes in the adult brain can precipitate neurologic and neuropsychiatric diseases. The identification of gene families with multiple genes that code for related yet distinct receptor isoforms has added a remarkable increase to the level of specificity and complexity that governs the transcriptional regulation of neurotransmitter receptors in the CNS. For instance, the diverse set of nineteen genes coding for the major inhibitory receptor in the brain, the GABA-A receptor, constitutes a gene family that displays an unusual degree of differential developmental and cell-specific gene regulation. Individual control over specific subunit gene expression leads to functional and pharmacological diversity that enables individual neurons to respond dynamically to alterations in membrane excitability via the alteration of the number or kind of synaptic and/or extrasynaptic inhibitory receptors. We employ a variety of proteomic and transcriptomic techniques, including RNA and chromatin immunoprecipitation (ChIP) high density sequencing, primary neuronal cultures and in vivo models to test hypotheses of disease etiology and potential strategies for novel molecular therapeutics that restore the balance of inhibition and excitation in the brain.
Identification of novel treatments for brain disorders
Our laboratory is also interested in the discovery of novel brain intracellular systems that may provide new therapeutic strategies for the treatment of epilepsy. Working together with our collaborators in Colorado in the Amy Brooks-Kayal laboratory, we have discovered a novel pathway whereby the neurotrophin brain derived neurotrophic factor (BDNF) regulates the activation of the JAK/STAT signaling system in neurons, a discovery that we have shown brings spontaneous seizure production after brain insult under the control of JAK/STAT inhibitors used now in human cancer treatment. We are currently screening unique natural product libraries in collaboration with the John Porco laboratory at BU and our collaborators and friends at UColorado to identify new molecules that may be efficacious in the future treatment of intractable epilepsies.
Molecular tools for probing brain network dynamics and their responses to pharmacological intervention
A new area for the laboratory has been the development of molecular tools that can serve as in vivo sensors for the activation or inhibition of gene regulatory pathways in animal models of disease and for monitoring the functional output of dynamic neural responses that can be used to advance the power of optogenetic manipulation. We have two projects ongoing in this area that use recombinant DNA tools to deliver proteins that interact in a dynamic way to signal the presence of specific intracellular responses upon behavioral manipulation.