黑料吃瓜资源

Our immune system is remarkably powerful. It quickly assembles teams of cells to eliminate threats inside our bodies. But sometimes, it hits the wrong target. Autoimmune diseases like lupus and multiple sclerosis result from friendly fire鈥攊mmune cells attacking healthy tissues and organs by mistake. New treatments and therapeutic targets are direly needed for these conditions.

Now, 黑料吃瓜资源 (CSHL) Professor Christopher Vakoc may have stumbled upon a new therapeutic target鈥攐ne hidden in plain sight. Vakoc and his team discovered that I魏B味, a well-studied protein in the immunology field, contains an overlooked sequence, which lets it activate key proteins in immune cells. While the sequence鈥攖he OCA peptide鈥攊s tiny, targeting it may have significant effects in reeling in immune cells gone haywire.

For years, I魏B味 was known for one important job鈥攃ontrolling NF魏B, a protein that’s crucial for mounting an immune response. But it turns out I魏B味 has dual functions. Vakoc鈥檚 team found it also activates another important family of immune proteins called POUs. And it does this through the OCA peptide. Firing up both immune reactions may ensure the quickest response to encroaching dangers鈥攁 vital trademark of our natural defenses.

鈥淭丑别 immune system is held in check most of the time,鈥� Vakoc says. 鈥淏ut the moment a pathogen arrives, it needs to very quickly adapt. The ability to respond within seconds is critical to eliminating bacteria, an invading virus, or even cancer. Time is of the essence.鈥�

Why has evolution assigned I魏B味 this moonlight job? Vakoc suspects it has something to do with the enormous number of tasks immune systems perform. While immune cells activate many of the same proteins, each cell also has its own duties. The duality of I魏B味 might provide our body鈥檚 defenders the versatility to rapidly switch between roles.

鈥淓volution often finds creative and efficient solutions to problems in life,鈥� Vakoc explains. 鈥淲e think the OCA peptide allows different types of immune cells to respond quickly, with the right genes at the right time and place. It’s all about personalizing the immune response for different cells in the body.鈥�

The discovery might form the basis for future immunotherapies against autoimmune disorders. Since the OCA peptide is well-defined and found in many immune cells, it could make for a prime drug target. And that鈥檚 where Vakoc will set his sights next.

鈥淭argeting I魏B味 via its OCA peptide would be expected to have interesting impacts on the immune system, with highly cell-type-specific effects,鈥� Vakoc says. 鈥淥ur future research will explore this question.鈥�

Written by: Luis Sandoval, Communications Specialist | [email protected] | 516-367-6826

Funding

National Cancer Institute, Pershing Square Sohn Cancer Research Alliance, National Institutes of Health, Department of Defense, CSHL-Northwell Health Affiliation

Citation

Alpsoy, A., Wu, X. S., et al., 鈥淚魏B味 is a dual-use coactivator of NF-魏B and POU transcription factors鈥�, Molecular Cell, February 2, 2024. DOI:

Core Facilites

鈥淭丑别 Functional Genomics Shared Resource offers services for functional screens and gene modulation using RNAi and CRISPR technologies. We also assist in the design and implementation of other screening modalities. The process of screening is designed to be a collaborative endeavor between the core and the investigator鈥檚 lab. The core offers custom RNAi/CRISPR library design and construction services.鈥� 鈥� Director Kenneth Chang, Ph.D.

鈥淭丑别 Sequencing Technologies and Analysis Shared Resource provides access to an array of high throughput Next Generation Sequencing (NGS) technologies. We offer cutting-edge technology alongside convenient in-house services for a broad range of genetic analysis.鈥� 鈥� NGS Director Sara Goodwin, Ph.D.

鈥淭丑别 Single Cell Genomics Core Facility brings cutting-edge single-cell technologies to collaborators both inside and outside of the Laboratory. We currently specialize in single-cell transcriptomics and offer assistance in a variety of gene expression workflows, including the latest in spatial gene expression profiling technologies.鈥� 鈥� Director Jon Preall, Ph.D.