Adenosine Modulation of the Bi-Directional Relationship between Sleep and Migraine - PROJECT SUMMARY This proposal describes as 5-year mentored career development and research plan that facilitates the transition of Dr. Sinifunanya Nwaobi to an independent clinician scientist. Dr. Nwaobi is a Pediatric Neurologist who specializes in Headache and Pain Medicine at the UCLA Goldberg Migraine Program. Her overall career goal is to focus on managing adult and pediatric headache while leading translational research that will directly impact her patients’ care. One main career objective is to approach headache and pain research through the lens of a glial biologist, with a focus on astrocytes. The research proposal elucidates the bi-directional relationship between sleep and migraine by examining the specific mechanisms by which sleep modulates migraine pathophysiology. Aim 1 interrogates how both homeostatic and circadian components of sleep impact acute and chronic migraine using three clinically relevant rodent models of migraine. Aim 2 examines astrocytic, neuronal, and receptor-specific adenosine signaling to identify a drug-targetable mediator of the sleep-migraine connection. This tailored proposal builds upon Dr. Nwaobi’s prior experiences in glial biology, while expanding her skillset to include novel technologies that allow for minimally invasive in vivo monitoring of brain activity which are broadly applicable to the field of neuroscience. This research proposal will also expand her expertise in electrophysiology, in vivo fiber photometry, and large data statistical analyses. She will gain increased research exposure to the fields of headache, sleep, and glial biology. This work lays the foundation for future studies that will be the topic of subsequent K- and R- funding proposals. Importantly, this career development plan provides Dr. Nwaobi with world-class mentorship from leading experts in fields of headache medicine, circadian physiology, and glial biology. This diverse mentorship works to ensure her successful transition to an independent clinician scientist, foster collaborative research, and maximize the translational impact of the proposed studies. Overall, the proposed career development and research plan will directly advance the field of migraine with a focus on targeting drug-modifiable processes, while advancing Dr. Nwaobi towards research independence as a clinician scientist in headache and pain medicine.
