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Defining the role of Pi16-expressing fibroblasts in mouse and human fibrosing skin disease

Award Number: K08AR085193
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Defining the role of Pi16-expressing fibroblasts in mouse and human fibrosing skin disease - PROJECT SUMMARY/ABSTRACT This proposal describes a 5-year research and career development plan that will enable Dr. Maxime Kinet to achieve his long-term goal of becoming an independently funded physician-scientist studying how different fibroblast subsets contribute to tissue homeostasis and fibrosing diseases. Currently, very little is known about how individual fibroblast subsets, identifiable in healthy tissues, differ in their responses and contribution to fibrosing skin disease. The proposed research will focus on uncovering the mechanisms by which the Pi16+ fibroblast subset, common to many organs in mammals, responds to and reduces fibrosis. Dr. Kinet will use a novel, fibroblast-subset-specific Pi16CreERT2 line to study this conserved subset. Additionally, he will apply this Cre line alongside a highly innovative in vivo CRISPR/Cas9 technique to enable interrogation of any genetic pathway in these cells. In Aim 1, Dr. Kinet will elucidate how Pi16-expressing fibroblasts molecularly respond to a fibrotic stimulus. Aim 2 will focus the mechanisms used by Pi16-expressing fibroblasts to reduce fibrosis in the overlying skin. In Aim 3, Dr. Kinet will leverage comprehensive single-nuclear and spatial transcriptomic technologies to identify how Pi16-expressing fibroblasts change in human fibrosing skin disease. The aggregate data will provide a major advancement in our understanding of how Pi16-expressing fibroblasts, a conserved subset across tissues and species, respond to and regulate fibrosis. During his post-doctoral work and as Assistant Professor in the University of California, San Francisco (UCSF) Rheumatology Division, Dr. Kinet has strategically sought out additional training and mentorship in cutaneous immunology and fibrosis. Under the primary mentorship of Dr. Michael Rosenblum, an expert in skin Treg biology, the candidate, co-mentors Drs. Dean Sheppard and Ari Molosky, and scientific advisors Drs. Julie Zikherman and Francesco Boin have developed a career development plan for Dr. Kinet to gain additional experience in state-of-the-art immunology and cutting-edge transcriptomic profiling, biostatistics, and scientific communication. To enhance Dr. Kinet’s training, a multidisciplinary advisory committee consisting of mentors and scientific advisors will meet biannually to review his progress and support his career development. The proposed training program draws on the combined resources of the Rosenblum Laboratory, the UCSF Immunology Training Program, and the UCSF Departments of Dermatology and Pathology. This will provide an ideal setting for Dr. Kinet’s transition to an independent investigator.


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 = $175,068 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/3/2026	NON-COMPETING CONTINUATION	$175,068
														Subtotal = $175,068

Issue Date FY: 2025 ( Subtotal = $176,148 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/24/2025	NEW	$176,148
														Subtotal = $176,148

Grand Total All Awards = $351,216

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Defining the role of Pi16-expressing fibroblasts in mouse and human fibrosing skin disease

Award Number: K08AR085193

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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