Wednesday, July 2, 2025 7/2/2025

Sensory neuron-skin interaction in health and disease

Award Number: K01AR080833
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Sensory neuron-skin interaction in health and disease - PROJECT SUMMARY My career goal is to lead an independent research group to investigate the pathology and resolution of pain to solve neuropathic pain problems. To achieve this goal, I propose to develop and use novel translational strategies to investigate neuron-substrate interactions in the skin layer using a combination of human and animal models of peripheral sensory neuropathy. My research focuses on a common type of peripheral sensory neuropathy induced by chemotherapy, which affects over 3 million people in the US alone. While chemotherapy- induced peripheral neuropathy (CIPN) develops in up to 80% of cancer patients treated with chemotherapeutics, there are no effective prevention or treatment strategies. Considering the dynamic extracellular environment of cutaneous sensory nerves and recent understanding that keratinocytes can also function as a nociceptor, it is vital to understand the maintenance and function of both neurons and keratinocytes to solve neuropathic pain. Hence, I propose to test the hypothesis that dysregulation of neuron and epidermal interactions underlie pathological progression of CIPN. Building from my recent work that identified protective roles of integrins in CIPN, my proposal has three aims that use cutting-edge tools and innovative multi-disciplinary approaches. In Aim 1, I will investigate neuron-substrate interactions and their regulatory mechanisms in a Drosophila in vivo CIPN model. I will use genetics and advanced microscopy approaches to label, manipulate, and detect subcellular changes in neuron to substrate contacts and link with functional changes in a CIPN model. Using integrins as a model to understand cell surface protein-mediated mechanisms underlying CIPN, I will characterize endocytic regulators that modulate surface protein expression mediating neuron-substrate contacts. In Aim 2, I will use human induced pluripotent stem cell (iPSC) technology to identify keratinocyte-nociceptive neuron interactions and cell-type-specific pathology in a co-culture CIPN model. Given species differences in sensory neurons, I expect that establishing a human model to investigate the impact of sensory neurons and extrinsic factors on pathological progression in CIPN will provide critical insights. In Aim 3, I will establish and validate a 3D human skin-nerve co-culture CIPN model to investigate neuron-substrate relationships and integrin-mediated protection. Because subtypes of nociceptive neurons target different epidermal layers and contribute to distinct pathology in peripheral neuropathy, a 3D engineered human skin will be incorporated in the model. This will allow me to investigate subtype-specific pathology and to resolve nociceptive neuron terminal degeneration and dysfunction in CIPN. This proposal will provide new insights into pathological progression and mechanisms mediated by neuron-substrate interactions and a strong foundation for my future research. As my primary expertise is in neuroscience using Drosophila models, investigating human neurons and epidermal cells requires new training in skin biology and stem cell biology. The proposed plan will significantly facilitate my career goal to solve intractable neuropathic pain problems in patients.


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: 2025 ( Subtotal = $125,442 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/28/2025	NON-COMPETING CONTINUATION	$125,442
														Subtotal = $125,442

Issue Date FY: 2024 ( Subtotal = $182,231 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	2	8/14/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$150,314
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	2/2/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$182,231
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	8/14/2024	NEW	-$81,046
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/1/2024	NEW	$0
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	1	8/14/2024	SUPPLEMENT FOR EXPANSION	-$69,268
														Subtotal = $182,231

Issue Date FY: 2023 ( Subtotal = $232,653 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	9/14/2023	SUPPLEMENT FOR EXPANSION	$107,211
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/25/2023	NEW	$125,442
														Subtotal = $232,653

Grand Total All Awards = $540,326

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Sensory neuron-skin interaction in health and disease

Award Number: K01AR080833

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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