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CoNDA Research Projects

Dr. Olga Taraschenko

The Role of Hippocampal Neurogenesis in the Development of Cognitive Deficits in Autoimmune Encephalitis with Seizures

Led by Dr. Olga Taraschenko, MD, PhD

Dr. Taraschenko completed her MD at National Medical University in Kiev, Ukraine. She received her PhD training in Neuropharmacology and Neuroscience as well as postdoctoral training under the mentorship of Stanley Glick, MD, PhD, at Albany Medical Center. Dr. Taraschenko then completed her residency in Neurology at Albany Medical Center and fellowship in Epilepsy at Emory University. During her clinical training she developed interest in autoimmune encephalopathies with seizures, a group of newly discovered disorders for which there were no effective treatments. Under the guidance of Dr. Raymond Dingledine, Department of Pharmacology at Emory, she established a research plan to study basic mechanisms of autoimmune seizures which has remained the focus of her laboratory. As an Associate Professor in the Division of Epilepsy, Dr. Taraschenko provides expert consultations for patients with epilepsy and directs the Comprehensive Epilepsy Center at UNMC. Her current research pursuits have been expanded to define the mechanisms of cognitive decline in patients with autoimmune encephalitis.

Study Overview:
This project will address a critical gap in understanding the correlates of chronic memory loss in autoimmune encephalitis with an emphasis on identifying and testing potential pharmacotherapies. Specifically, the proposal will investigate if antibody-induced seizures alter neurogenesis in autoimmune anti-NMDA receptor encephalitis and whether reduced neurogenesis occurs in parallel with impairment of memory in mice.

Specific Aims:

  1. Establish if seizures and memory impairment induced by neuronal autoantibodies in anti-NMDA receptor encephalitis are accompanied by depletion of the stem cell population in the hippocampus of mice
  2. Establish the role of inflammation in aberrant neurogenesis and memory loss in autoimmune encephalitis with seizures

Impact:
Successful completion of this project will improve our understanding of the pathogenesis of cognitive failure in autoimmune encephalitis and other chronic autoimmune disorders of the brain and will lay the groundwork for identifying potential pharmacotherapies for this devastating condition with a focus on harnessing neuroinflammation. 

 

Dr. Leonardo da Silva Augusto

The Role of Host Amino Acid Metabolism in Behavioral Changes during Latent Toxoplasmosis

Led by Dr. Leonardo da Silva Augusto, PhD

Dr. Leonardo Augusto completed his PhD at the Federal University of Sao Paulo and had his postdoctoral training at Indiana University School of Medicine. His lab aims to understand the host cell metabolism changes in neuroinflammation, neurodegeneration caused by chronic Toxoplasma gondii infection.

Study Overview:
This proposal addresses the function of amino acid metabolism in neuroinflammation, neurodegeneration caused by chronic toxoplasmosis.

Specific Aims:

  1. Identify the role of host amino acid content in neurological alterations caused by Toxoplasma infection.
  2. Elucidate the mechanism by which amino acid metabolic pathways coordinate theneuroinflammation and neurodegeneration of chronically infected mice.

Impact:
These studies capitalize on our novel finding that Toxoplasma infection depletes host amino acids in ways that facilitate the infection. Resolving the mechanism underlying this discovery will provide much needed insight into how the parasite establishes a chronic infection and causes neurological alterations putting us in a better position to develop novel therapies to treat chronic toxoplasmosis in patients.

 

Dr. Peng Zhong

Hypothalamic Sleep-Wake Neuron Defects in Alzheimer's Disease

Led by Dr. Peng Zhong, PhD

Dr. Zhong completed his PhD in Biomedical Sciences at the Medical College of Wisconsin in 2015. His research aims to unravel the neural underpinnings of causal relationship between sleep disturbance and neurodegenerative disorders with the ultimate goal of learning how to repair the diseased nervous systems. Taking advantage of multiple state-of-the-art techniques (e.g., gene profiling, virus-mediated circuit tracing, in vivo calcium imaging/optrode recording, ex vivo patch clamp recording, optogenetic/chemogenetic manipulation and gene manipulation), his work takes a multifaceted but integrated experimental approach for interrogating the neural circuits controlling sleep and studying the pathophysiology of sleep circuits in the generation of sleep disorders and neuropsychiatric/neurodegenerative disorders.

Study Overview:
Sleep problems and Alzheimer’s disease (AD) are interrelated and bidirectional. Understanding sleep circuitry abnormalities in AD could improve our understanding of its pathology and provide insight into the novel therapeutic approaches for this neurodegenerative disease. We will utilize the powerful systems neuroscience techniques to investigate whether and how lateral hypothalamic REM sleep-active melanin-concentrating hormone (MCH) neurons become dysfunctional in AD.  

Specific Aims:

  1. Determine whether MCH neurons are dysfunctional in the PS19 AD mouse model of tauopathy.
  2. Determine whether chemogenetic inhibition of MCH neurons ameliorates dysregulated sleep and cognitive deficits in PS19 mice.

Impact:
The results of this project will help open the door to the development of circuit-based therapeutic interventions for AD-related sleep disorders and cognitive impairments.