P01AI179405

Lupus Nephritis: Novel Insights in the Pathogenesis and Treatment - Overall Abstract

Little is known about the pathogenesis of lupus nephritis (LN), particularly as it relates to the initiation and propagation of the inflammatory response which accounts for the development or end stage renal disease. LN may complicate up to two thirds of patients with systemic lupus erythematosus with higher rates commonly seen among minorities and children.

Besides the needle kidney biopsy, we lack tools that reflect tissue pathology with fidelity. Although two drugs have been recently approved to treat patients with LN, all treatment protocols involve systemic administration of drugs or biologics which are laden with side effects and limited clinical efficacy.

Ample evidence has revealed that kidney resident cells and newly formed high endothelial venules in the presence of an autoinflammatory environment, upregulate molecules which account for the ensuing inflammation and cell damage, while in their absence, kidney damage is averted. These molecular changes can be recorded in parallel in podocytes and tubular epithelial cells in the urine.

This proposal will test the hypothesis that interaction of constituents of the immune system with kidney resident cells and the ectopically formed high endothelial venules, determines the development of inflammation and injury in the setting of LN. Corollaries of this hypothesis are that kidney resident cells can serve as gateways for the administration of targeted therapeutics for the treatment of LN and that kidney tissue pathology can be recorded with high fidelity in the urine cells of patients with LN.

There are 2 projects in this proposal: 1) Interplay between Autoimmune Effectors and Kidney Resident Cells in Lupus Nephritis and 2) Newly Formed High Endothelial Cells in the Kidney- Pathogenesis and Implications in Lupus Nephritis.

The proposal will be supported by 3 cores: The Administrative Core will be responsible for regulatory compliance, budget management, scheduling meetings. The Nanoparticle Immune Delivery Core will be responsible for the construction of nanoparticles loaded with drugs and biologics and tagged with antibodies for cell-specific delivery. The Single Cell, Spatial Transcriptomics and Bioinformatics Core will perform single cell transcriptomics studies and will provide statistical and bioinformatics support.

This proposal through extensive synergistic plans between the project leaders brings forward novel and significant elements in the study of the pathogenesis, treatment and biomarker development in patients with LN.

Beth Israel Deaconess Medical Center

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Boston, Massachusetts 022155400 United States

Single Zip Code

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-22-225)

Amendment Since initial award the total obligations have increased 99% from $2,247,493 to $4,476,762.