Chemical and Biochemical Approaches for the Study of Anesthetic Function Part B

Originally aspiring to be a marine biologist while at the University of Miami, Rod elected instead to join the ranks in hyperbaric medicine after graduating from Northwestern University Medical School. Since the only formal training program existed in the military, he became a US Naval officer, ultimately spending most of his time performing hyperbaric medicine research at the Naval Submarine Medical Research Laboratory in Groton, CT. Aiming to continue in this area, but in a more academic setting, he returned to civilian life as an anesthesia resident at the University of Pennsylvania, in large part because of the renowned Institute for Environmental Medicine at Penn. But the ability to more definitively answer questions persuaded Dr. Eckenhoff to pursue basic science training in the Andrew Somlyo lab at Penn., where he accidently discovered an approach to measure subcellular concentrations of anesthetics. This launched him in an entirely new direction, ultimately discovering anesthetic photolabeling, and adapting a series of traditionally biophysical approaches to the study of anesthetic mechanisms. Receiving his first NIH grant in 1991, Dr. Eckenhoff assembled an interdisciplinary group to study anesthetic mechanisms, and just a few years later, led a program project grant to funding on the first attempt. This grant is now in its 18th year and has evolved to now include seven different institutions across the country. The study of anesthetic mechanisms opened new doors into adverse effects, such as possible interactions with Alzheimer neuropathology, an issue that has gained considerable traction over the past decade. Finally, Dr. Eckenhoff has had the privilege of mentoring dozens of outstanding physicians, physician/scientists and basic scientists over the last thirty years.

Computational approaches 1. Physical accuracy leads to biological relevance: Best practices for simulating ligand-gated ion channels interacting with general anesthetics 2. Computational approaches for studying voltage-gated ion channels modulation by general anesthetics 3. Anesthetic parameterization 4. Pharmacophore QSAR, QM, ONIOM 5. Kinetic modeling of electrophysiology dataGenetics and model organisms 6. General genetic strategies 7. Worms 8. Flies 9. Tadpoles 10. Zebrafish 11. MicePhotolabeling 12. Mass spect ID of adducts 13. Photolabeling protection/competitionXenon 14. Xenon-protein interactions 15. Xenon gas delivery/recovery procedures 16. Hyperpolarized Xe-129 MRI 17. CT imagingElectrophysiology 18. Native system electrophysiology (slices, cells, in vivo) 19. Voltage-gated ion channels (Kv, Nav) 20. Ligand-gated ion channels 21. Other channels (HCN/K2P/TRP)Structural Approaches 22. Soluble proteins 23. Membrane proteins24. NMR 25. Time-Resolved Neutron Interferometry and the Mechanism of Electromechanical Coupling in Voltage-Gated Ion ChannelsEvolving Biophysical Technologies 26. Fluorescent Anesthetics 27. Investigation of anesthetic-protein interactions by a thermodynamic approach 28. Tissue/organism EPR 29. Lipids, Membranes and Pressure reversalIn vivo technologies; established and evolving 30. Optoanesthesia 31. Optogenetics, Chemogenetics 32. Genetic reporters of neuronal activity: c-fos, genetically encoded calcium indicators 33. Genomics and Proteomic Techniques 34. Neurochemistry of Anesthetic States 35. Electroencephalography 36. PET 37. Drug discovery and development 38. The use of glutamatergic anesthetics (ketamine, nitrous oxide and xenon) in depression 39. Brain Imaging Using Hyperpolarized 129Xe MRI