Andrew H. Ahn - US grants

DESCRIPTION (provided by applicant): Andrew H. Ahn, M.D., Ph.D. is a neurologist with prior training in molecular and cell biology. His K08 Mentored Clinical Scientist Career Development Award will be used to develop a career in academic neurology with a research focus on understanding the basic mechanisms of migraine. Migraine is a significant neurological condition that affects over 27 million people in the United States with an annual cost of up to $13 billion in lost wages and medical care. Research Plan: Dr. Ahn will study the mechanism of action of the triptans, serotonin receptor subtype-selective agonists used in the treatment of migraine headache. He plans a series of experiments based on his preliminary findings that a triptan receptor, serotonin receptor subtype 5HT1 D, is concentrated within the central and centrolateral nuclei of the amygdala, regions of the brain with prominent roles in pain processing. He will test the hypothesis that these terminals within the amygdala originate in the dorsal raphe, a structure also relevant to pain modulation and specifically known to synthesize 5HTID receptor. He will then test the hypothesis that triptans affect pain processing through their activation of 5HTID receptors in the amygdala. To do this, he will determine the ability of triptans to interfere with a behavioral model of learned pain-aversive behavior and will follow up on these results with direct electrophysiological recordings of evoked activity in the trigeminal nucleus. Developmental Plan: Dr. Ahn has joined the laboratory of Allan I. Basbaum, Ph.D. to gain an understanding of the basic mechanisms of pain, as well as to learn the relevant techniques of neuroanatomy, physiology and pain behavior in animal models. In addition, UCSF provides a unique training environment through an interdisciplinary pain center with a well-developed academic program. The proposed plan draws upon the expertise of the Basbaum Laboratory in the anatomical, behavioral and physiological techniques that will train Dr. Ahn's to become an independent investigator. He will also draw upon the longstanding pain research and physiology skills of Howard L. Fields, M.D., Ph.D. as a co-sponsor. Dr. Ahn's professional goals are to obtain a tenure-track academic position in neurology, and to investigate the basic mechanisms of migraine in his research laboratory through independent, investigator-initiated funding. He has the wholehearted encouragement of his institution in applying for a clinician-investigator position with a focus on migraine research in the coming years.

DESCRIPTION (provided by applicant): Migraine is a prevalent and disabling disorder that continues to confound best available medical therapy. An important obstacle to new more effective therapy is that we lack critical insights as to the relevant neurobiological targets. This is because the basic mechanisms contributing to this disorder remain elusive, and prevailing theories of the pathophysiology of migraine are based upon indirect or conflicting lines of evidence. Given what little direct evidence supports our understanding of migraine, any fundamental insight into the critical anti-migraine actions of sumatriptan action in the brain would be of great significance to our understanding of the disorder and the rational design of new therapies. The overall goal of this project is to elucidate the neurobiological actions of the migraine-specific drug sumatriptan. The inhibitory actions of sumatriptan in the periphery, on neurogenic inflammation and sensory neurons, are well described, but the mechanisms of sumatriptan in the brain remain virtually unexplored. This project focuses on the action of sumatriptan on pain-related circuits within the amygdala, and its influence on the affective-emotional processing of pain, through the activation of the 5HT1D receptor. Importantly, because a central clinical feature of migraine is the disturbance of the affective component of all sensory modalities, the modulation of the affective-emotional processing of pain by sumatriptan within the amygdala could potentially be a critical site for the anti-migraine activity of sumatriptan, and could be an important target for migraine therapy in the future. This applicant for a K02 Independent Scientist Career Development Award is a physician scientist with a longstanding commitment to a career in neuroscience research. This K02 award will support his continued career development and research that will lead to obtaining peer-reviewed, independent investigator-initiated funding.