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NY Genome Center Moves into New Phase as Executive Resigns, Project Proposals Get Underway

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Three months after the New York Genome Center appointed Bob Darnell as its first president and scientific director, the organization appears to be entering a new phase, with the departure of its founding executive director, Nancy Kelley, and emerging plans for a variety of scientific projects.

The center last week announced the departure of Kelley, who had been the driving force behind its creation. At the time of Darnell's appointment last November, she had also taken on the role of chief operating officer (IS 12/4/2012). Kelley will remain a director and an advisor to the NYGC.

According to a statement from the center, Darnell "will build on the strong foundation established by Ms. Kelley to deliver NYGC's vision of collaborative genomics research," both to improve disease treatment and to provide sequencing and bioinformatics services to researchers in and around New York.

Kelley said in a statement that the center "is now well positioned to become a world-class collaborative center for translational genomic research under the strong leadership of Dr. Darnell," adding that it is "an appropriate time" for her to "pursue other endeavors."

Officials at NYGC declined to comment on whether her positions of executive director and chief operating officer will be refilled.

Neither NYGC's board of directors nor its executive committee were involved in the decision on Kelley's departure, according to a scientist from one of the center's institutional founding members who is familiar with the situation.

He called the development a "natural transition," suggesting that the organization could probably not sustain two leaders whose visions differed somewhat. "Bob definitely has a path he wants to push and it's not really the path Nancy had always talked about," he said.

Last month at the Advances in Genome Biology and Technology conference in Marco Island, Fla., Darnell provided a first glimpse of various projects, all still at the planning stage, that he would like the New York Genome Center to take on.

In an interview during the meeting, Darnell told In Sequence that he spent much of the last several months talking to scientists and clinicians at the center's member and associate member institutions.

Based on feedback from those discussions, Darnell has identified two sets of pilot projects: one set headed by the center that will involve collaborations with member institutions; and another set of projects spearheaded by member institutions who will be conducting their work through the genome center.

Member institutions include Cold Spring Harbor Laboratory, Columbia University, Cornell University/Weill Cornell Medical College, the Jackson Laboratory, Memorial Sloan-Kettering Cancer Center, Mount Sinai School of Medicine, New York-Presbyterian Hospital, the New York University School of Medicine, North Shore-Long Island Jewish Health System, Rockefeller University, and Stony Brook University. The Hospital for Special Surgery is an associate member.

Both project sets are "evolving ideas," he said, that will take advantage of the center's genome sequencing and bioinformatics resources, as well as its expertise in dealing with the "massive amount of data in a very state-of-the-art and intelligent way."

While funding for the projects has not yet been secured, Darnell said he is confident they will get off the ground this year.

Among the projects to be initiated by the genome center itself is a study of traumatic brain injury in professional athletes. The idea is to look for markers that could distinguish between significant and non-significant head trauma and could provide prognostic information. Scientists would draw blood before and after a game, and sequence both samples if a player sustains a concussion during the game.

The pathology of traumatic brain injury overlaps with that of Alzheimer's and other neurodegenerative diseases, Darnell said, so any findings could potentially translate to those conditions, as well as to non-sports-related traumatic brain injury. He declined to provide details about the sequencing approach to be used in this project. However, he noted that as sequencing technologies become smaller and more user-friendly, he could envision diagnostic sequencing tests for brain injury at the point of care.

Another project the NYGC plans to pursue is a glioblastoma study, in which four institutional founding members have expressed an interest. This project would involve whole-genome sequencing of archived samples from all patients who died of glioblastoma in the New York area within the last 10 years – several thousand samples in total -- in order to gain a deeper understanding of the molecular pathways involved in their disease.

Coupled with this retrospective study would be a clinical trial that would use existing drugs and, possibly, drugs in late clinical development to target specific pathways in current glioblastoma patients, based on mutations found in their tumors.

"The idea would be a clinical outcomes trial, as opposed to a standard clinical trial where you're comparing best care vs. best care plus one new variable," Darnell explained. "This would be to take each patient as a de novo experiment."

The trial would involve a few dozen patients initially for proof of concept and would be a collaborative clinical study between several academic institutes in New York, he said. It would be concurrent with the retrospective study. Glioblastoma patients face a dire prognosis – the median survival is currently only 12 months – so the potential benefit of such a "very aggressive trial" that involves multiple drugs would likely justify the risk, he said. The center is working on IRB approval and funding for the project, he said, which would be overseen by Rockefeller University Hospital, which he said is "ideally suited as a hospital to look over an unusual study like this and move forward quickly."

For frozen glioblastoma samples, this project would also involve RNA-seq, as well as HITS-CLIP, a method to map protein-RNA binding sites that Darnell's lab invented.

A third projected to be initiated by the NYGC is in the area of paraneoplastic neurological disorder, which has been a focus of Darnell's own research for many years. In a subset of the disease, common tumors start expressing neuron-specific proteins, which triggers an immune response against the tumor. Later, the immune system breaks the blood-brain barrier and starts attacking neurons expressing the same proteins, resulting in an autoimmune disease that is similar to multiple sclerosis.

Darnell and his collaborators would like to compare the genomes of tumors and the genomic profile of the immune system between patients who do or don't develop the anti-tumor immune response. In particular, they are interested in pediatric neuroblastoma, where tumors disappear spontaneously without treatment in some patients, who they want to compare to patients where this does not happen.

In terms of projects initiated by institutional founding members, Darnell said there is "great interest" among several members in infectious disease, specifically a microbiome project related to host-immune interactions. He said the NYGC could be instrumental in helping these groups come together and secure funding for the project from the National Institutes of Health. "It's a nice example of how the genome center can forge collaborations in the city that otherwise absolutely would not be happening."

In addition, several founding members have expressed an interest in neurodegenerative disease, and some have talked about forming a consortium to study amyotrophic lateral sclerosis. Darnell provided no further details at this time but noted that an ALS whole-exome sequencing project is ongoing already that is spearheaded by researchers at Columbia University.

While funding for NYGC's projects still needs to be raised, the center has received "tremendous support, both intellectually and in terms of possible resource support" from Illumina, Darnell said, and has been interacting with other technology providers that "may play unexpected roles in collaborating with some of these projects."

Besides providing sequencing and computational resources to its members, the center plans to offer bioinformatics education and is currently putting together bioinformatics courses, one of them potentially in collaboration with Cold Spring Harbor Laboratory.

The NYGC is still on track to start moving into its permanent location in downtown Manhattan this spring. Building renovations are "on time and on budget," Darnell said, adding that office space will be ready in May and the "wet lab" component in June.

To avoid interruptions in sequencing services, the center's pilot lab, currently located at Rockefeller University, will only move around June or July when "everything is up and running," he said.

As reported earlier, the NYGC's permanent location will also include a CLIA-certified laboratory. The center is currently seeking to hire a director of molecular diagnostics to help establish and build out a diagnostics laboratory, and to develop and perform next-gen sequencing based molecular diagnostics assays in accordance with CLIA and New York State regulations, according to its website.

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