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Hospital for Special Surgery Starts with RNA, CHIP-Seq Projects under New RA and Lupus Genomics Center

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New York's Hospital for Special Surgery is planning five years of sequencing-based research, starting with functional genomics and then moving later to whole-genome sequencing at its new Genomics Center.

The hospital announced the creation of the new center, funded with $5.6 million from The Tow Foundation, last month to study rheumatoid arthritis and systemic lupus erythematosus, with the aim of developing more effective therapies.

According to Lionel Ivashkiv, the associate chief scientific officer at HSS and director of the new center, the project's first goal and first efforts will be to use methods like ChIP-seq and RNA-seq in functional genomic research that the center hopes will help illuminate how genes and the environment interact in these two diseases.

Researchers, including investigators at HSS, have already discovered a number of proteins that play a role in rheumatoid arthritis and lupus that have led to advances in treatment.

With the new center, the hospital is hoping to use sequencing to understand the regulation and function of the genes associated with many of these proteins, and to identify new genes associated with lupus and rheumatoid arthritis that may lead to more effective treatments with fewer side effects. According to the group, the new center expects to be able to start testing new treatments in animal models by the fourth year of the grant.

"We'll be doing next-gen sequencing, but using techniques like ChIP-seq and RNA-seq to analyze how genes are regulated and expressed, focusing on these autoimmune-associated genes," Ivashkiv told CSN this week.

"In terms of clinical relevance, what we are doing is trying to understand gene-environment interaction using these high-throughput sequencing approaches," he added. "What we hope is that we can identify new therapeutic targets that would allow us to modulate gene expression in these diseases."

According to Ivashkiv, the hospital plans to eventually work with the New York Genome Center, but it has not yet begun that collaboration. Currently, he said, sequencing is being done at Weill Cornell Medical Center on an Illumina platform.

He noted that the New York Genome Center is just getting started, "so currently we have been working with the epigenomics core at Weill Cornell. We plan to continue that collaboration, too, but once [NYGC] is fully operational, we'll be working with them as well," he said. HSS is an associate founding member of the NYGC.

Ivashkiv said that his team hopes to perform several hundred sequencing runs in the first few years of the project, focused on functional genomic analyses.

In the later years of the grant, Ivashkiv said the new center also plans to start doing whole-genome sequencing to try to look at variation among lupus and RA sufferers and how it may be linked to therapy response or prognosis to help better personalize treatment. "That's a longer-term goal," he said.

"[This] is a very complex undertaking, but we think that it would also have a very big impact on improving patients' lives," he said in a statement from the hospital.

According to HSS, the new Genomics Center will have an estimated 20 scientists and will recruit four genomics fellows, a computational biologist, and a senior genomics researcher who will interact closely with NYGC staff. In the future, research may expand to other autoimmune and musculoskeletal diseases, the hospital said.

Ivashkiv also said an important step in moving toward whole-genome sequencing will be hiring a dedicated expert in that area to the center.

"Before we start doing whole-genome sequencing on our patients we need to recruit another scientist to the center with expertise in that, which we have plans to do."

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