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.
