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The Serine Protease HTRA1 Antigen: A Gateway to Elucidating Membranous Nephropathy Pathogenesis and the Targeting of Antigen Epitopes

Award Number: K23DK132487
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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The Serine Protease HTRA1 Antigen: A Gateway to Elucidating Membranous Nephropathy Pathogenesis and the Targeting of Antigen Epitopes - Abstract Primary membranous nephropathy (MN) is a major cause of nephrotic syndrome and kidney diseases. This autoimmune condition is characterized by the accumulation of immune complexes along the glomerular basement membrane (GBM). What triggers autoantibody production and its contribution to organ damage in MN remains incompletely understood. As such, further understanding of these pathological events could enable timely diagnosis and an overall improvement of treatment outcome in MN. Our previous interdisciplinary proteomic approach identified the serine protease HTRA1 as a novel autoantigen in MN. In this “Mentored Clinical Scientist Research Career Development (K23) Award”, mechanistic studies will be implemented to identify the precise pathogenic HTRA1 epitopes targeted by autoantibodies and their impact on HTRA1 protein function (Aim 1). Furthermore, contributions of HTRA1 autoantibodies as well as HTRA1 antigen accumulation to disease development will be investigated in newly developed animal models of MN (Aim 2). This five-year proposal aims to support the transition of the candidate from a junior physician scientist to an independent investigator in nephrology under the mentorship of leading experts in immunology, nephrology, and other relevant fields (Drs. Haecker, Beck, and Hageman). Building upon the candidate’s strong clinical experience (running the glomerular disease clinic at the University of Utah and utilizing biospecimens from the national MN clinical research network of CureGN, ARUP, and Arkana laboratories) and prior research exposure in glomerular disease, various intensive training modules will be designed to refine his scientific knowledge. Career development training will also be implemented to prepare the candidate with the necessary communication and leadership skills to become an independent investigator. Lastly, access to ample resources to support the aforementioned scientific studies and educational programs will ensure a timely successful execution of this proposal, allowing the candidate to begin his career path of scientific independence.


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 = $174,960 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/1/2025	NON-COMPETING CONTINUATION	$174,960
														Subtotal = $174,960

Issue Date FY: 2024 ( Subtotal = $174,960 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/16/2024	NON-COMPETING CONTINUATION	$174,960
														Subtotal = $174,960

Issue Date FY: 2023 ( Subtotal = $176,460 )
2023	2023	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/21/2023	NEW	$176,460
														Subtotal = $176,460

Grand Total All Awards = $526,380

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The Serine Protease HTRA1 Antigen: A Gateway to Elucidating Membranous Nephropathy Pathogenesis and the Targeting of Antigen Epitopes

Award Number: K23DK132487

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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