P01AI179251

Integrated Program for Cutaneous Immune-Stromal Interactions in SLE (IPCISS) - Project Summary/Abstract (Overall)

Systemic lupus erythematosus (SLE) with its associated skin inflammation remains a difficult-to-treat disease with frequent flares induced by ultraviolet (UV) light exposure.

It is critical to better understand disease mechanisms in order to build effective, personalized, non-toxic therapeutic strategies.

In the past ten years, our work and others' have identified a critical role of the skin itself in contributing to the propensity of disease in SLE patients.

Indeed, keratinocytes (KCs) are now recognized as critical contributors to chronic interferon (IFN) production and as part of a stromal-immune loop that drives disease.

We will build the Integrated Program for Cutaneous Immune-Stromal Interactions in SLE (IPCISS) to further facilitate and synergize the groundbreaking interdisciplinary basic and translational research at the intersection of dermatology and rheumatology that we have built at U-M.

The specific goals of our program are to (Project 1) build on our strengths in multi-omic informatics to fully define stromal-immune interactions in SLE skin, examine how spatial relationships modify the inflammatory response and identify the epigenetic contributions to inflammatory memory within SLE skin and (Project 2) relate these stromal-immune cell interactions to the pro-inflammatory UV response, examine how extracellular vesicles serve as critical cellular communication modulates after UV exposure in SLE, and study the role of type I IFN and UV light in epigenetic modification of keratinocyte inflammatory memory before and after the onset of SLE.

Further, to integrate and innovate data pipelines and analyses to be shared between the projects, we will establish the Bioinformatics and Integrated Omics Pipeline for Stromal and Immune Interaction (BIOPSII) core to dissect mechanism and gene-chromatin interactions in SLE patient skin.

Given the impactful and collaborative basic, translational, and clinical research undertaken by the project PIs, we are uniquely positioned to create a strong and lasting impact in systemic and cutaneous lupus and related fields.

The administrative core will provide leadership, oversight, and structure for the U-M IPCISS, including building program synergy through integrated project meetings and providing common management for the program.

In addition, the program's administrative core will host a robust enrichment program, which includes a visiting speaker series, an annual symposium, and a patient engagement program to promote diversity in SLE research.

There is strong institutional and departmental support for the IPCISS.

In summary, this program aligns with the NIAID P01 mission to support synergistic scientists who, through an interdisciplinary team science approach, will address a highly significant translational research challenge.

Here, we will further synergize our work in stromal-immune interface in SLE skin disease in order to better define disease mechanisms and accelerate new discoveries to ultimately benefit patients.

Regents Of The University Of Michigan

NOT APPLICABLE

93.855 - Allergy and Infectious Diseases Research

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

Ann Arbor, Michigan 481082744 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 $1,540,008 to $3,060,338.