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Striatal Interneuron Dysfunction: Uncovering the mechanistic basis of autism spectrum disorder in Dravet Syndrome

Award Number: K08NS144513
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Striatal Interneuron Dysfunction: Uncovering the mechanistic basis of autism spectrum disorder in Dravet Syndrome - PROJECT SUMMARY This K08 mentored research career development award proposal details a robust training program to position me to lead an independent R01 funded research program focused on the mechanisms of neurodevelopmental disorders. I am an Instructor in the Division of Neurology at The Children's Hospital of Philadelphia (CHOP). My clinical and research interests converge at the intersection of neurogenetics, autism and epilepsy. My prior research experience in the laboratories of Dr. Rafael Yuste at Columbia University and Dr. Adam Carter at New York University built my expertise in anatomical analysis, brain slice electrophysiology and optogenetics focused on the study of GABAergic interneurons and cell-type specificity of neural circuit connectivity. This proposal will advance my scientific training in cellular and circuit neuroscience to include animal models of neurodevelopmental disorders, in vivo two photon imaging integrated with head-fixed behavior, advanced genetic techniques and machine learning analysis of spontaneous behavior. I will be mentored by Dr. Ethan Goldberg, Associate Professor of Neurology and Neuroscience at CHOP, and Dr. Marc Fuccillo, Associate Professor of Neuroscience at The University of Pennsylvania (UPenn) who have co-mentored my NIH NINDS R25 fellowship. Dr. Goldberg's expertise in animal models of epilepsy, electrophysiology, and 2-photon calcium imaging complements Dr. Fuccillo's expertise in animal models of autism, striatal circuitry, quantitative behavioral analyses and in vivo neural recordings. Additionally, Dr. Goldberg is a highly successful physician scientist himself who was a prior K08 awardee who will provide invaluable career mentorship. I will receive additional mentorship and intellectual development from my advisory committee and the vibrant neuroscience and autism research communities at CHOP and UPenn. This proposal aims to identify mechanisms of autism in a mouse model of Dravet Syndrome (DS), a genetic neurodevelopmental disorder presenting with infantile onset epilepsy and high rates of autism. I will uncover the cellular pathophysiology of DS in subtype-specific striatal interneurons (INs) and investigate how this impacts excitation-inhibition balance in the striatum. I will then use in vivo 2P imaging in the striatum to reveal the impact in different cell types on neuronal activity during distinct behavioral states and neural encoding of goal-directed behavior. This will be the first use of in vivo 2P imaging in the striatum in a disease model. Finally, I will identify behavioral correlates of striatal IN dysfunction and test the contribution of distinct striatal IN subtypes to behavior using a novel intersectional genetic approach to selective gene loss or re-expression. Together training in these cutting-edge approaches combined with the exemplary resources available to me at CHOP and UPenn will prepare me for independence as a physician scientist making crucial discoveries to improve our understanding and therapeutic approaches to neurodevelopmental disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $221,400 )
2026	2026	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/11/2026	NEW	$221,400
														Subtotal = $221,400

Grand Total All Awards = $221,400

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Striatal Interneuron Dysfunction: Uncovering the mechanistic basis of autism spectrum disorder in Dravet Syndrome

Award Number: K08NS144513

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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