Neuronal Chloride Transporters in Health and Disease

Dr. Tang is a Simons postdoctoral scholar at the Massachusetts Institute of Technology in Cambridge. As part of The Whitehead Institute for Biomedical Research, he is a member of Dr. Rudolf Jaenisch’s lab, a world-renowned pioneer of transgenic science and a Whitehead founding member. His current research focus is the identification of drugs and chemical compounds that increase KCC2 expression, a neuronal chloride transporter implicated in Rett syndrome, a severe autism spectrum disorder primarily affecting young girls. He is known in the neurodevelopment field for his seminal work with human stem cell-derived neurons linking a reduction in chloride transporter expression to Rett syndrome pathogenesis, providing compelling evidence that disruptions in neuronal chloride transporters and excitation/inhibition balance may be a main cause of autism. Dr. Tang holds a position at the Simons Center for the Social Brain and holds research funds from the Rett Syndrome Research Trust.

• 1. Introduction: A historic overview of chloride transporter researchPart I: Function of neuronal chloride transporters in regulating neuronal chloride homeostasis and brain development2. Methods for investigating the activities of neuronal chloride transporters3. The relationships between neuronal chloride transporter activities, GABAergic inhibition, and neuronal excitability4. Chloride transporter activities shape early brain circuit development5. Regulation of neuronal cell migration and cortical development by chloride transporter activitiesPart II: Function of KCC2 in regulating excitatory synapse development6. KCC2 regulates dendritic spine development7. Transport-dependent and independent functions of KCC2 at excitatory synapses8. KCC2 is a hub protein that balances excitation and inhibition Part III: The molecular and cellular biology of neuronal chloride transporters9. Structures of KCC and NKCC family of chloride transporters in relationship to their functions10. Expression pattern of neuronal chloride transporter in different brain regions and sensory organs during development11. Post-translational modification of neuronal chloride transporters12. Protein interaction partners of neuronal chloride transporters13. Genetic and environmental regulators of chloride transporter gene expressionPart IV: Linking neuronal chloride transporter deficiencies to nervous system diseases14. The involvement of neuronal chloride transporter deficiencies in epilepsy 15. Deficiency in chloride transporter cause cardiac and respiratory abnormalities and SUDEP16. Impaired chloride transporters following brain injury and cerebral palsy17. WNK-SPAK/OSR1-CCC Signaling in Ischemic Brain Damage 18. The role of chloride transporters in neuropathic pain and spinal cord injury19. Neuronal chloride homeostasis and nerve injury20. Disruptions in Chloride transporters in autism spectrum disorders21. Chloride transporters in early brain development and Down syndrome 22. Alterations in chloride transporter activity in stress and depression23. The relationships between neuronal chloride transporters, brain aging, and neurodegenerative diseasesPart V: Development of therapies targeting neuronal chloride transporters24. Gene therapy approaches to restore the expression levels of Chloride transporters25. Utilization of NKCC1 blockers to treat brain disorders26. Quest for pharmacological regulators of KCC2