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CSHL, North Shore-LIJ Pact Marries Omics Research, Clinical Oncology to Speed Rx Discovery

NEW YORK (GenomeWeb) – Cold Spring Harbor Laboratory and the North Shore-LIJ Health System have announced a strategic partnership that will pair CSHL's basic and translational cancer research capabilities — particularly its omics expertise — with North Shore-LIJ's growing clinical cancer program, which includes more than 16,000 new cancer cases annually across the New York metropolitan area.

The partnership will be supported with more than $120 million over the next 10 years from undisclosed investors, and will be CSHL's first comprehensive clinical-oriented collaboration, which is expected to enable the institution to more quickly move its basic biomarker and therapeutic discoveries to the clinic, CSHL Director of Research David Spector told GenomeWeb.

"I think this more structured back and forth between clinicians and basic scientists will really allow us to make tremendous leaps forward … that would probably not be possible with the more casual type of relationship that exists today," Spector said. "By working together in this context, we can make great strides to identify great targets, mechanisms, and ultimately to help treat and cure patients."

Although oncology biomarker discovery and therapeutic development will be the main thrust of the collaboration, the organizations also plan to use funding to develop a new clinical cancer research unit at the North Shore-LIJ Cancer Institute's headquarters in Lake Success, NY, and to recruit and train more clinician-scientists in oncology.

"We plan to hire clinician scientists at North Shore-LIJ who have expertise in Phase I clinical trials [which] will help us in our translational research," Spector said. In addition, the partners plan to support clinical fellows from North Shore-LIJ healthcare system who want to work in basic science laboratories at CSHL. "The clinical fellow will provide some insight from the clinic, and he or she will gain some basic science insight, so again this will hopefully bridge the two groups," Spector noted.

As an example of the type of translational research at CSHL that could benefit from a clinical oncology conduit, Spector cited the work of CSHL scientists Chris Vakoc and Greg Hannon. Vakoc, Spector said, "has identified a battery of potential targets and has developed [short-hairpin] RNA libraries" in conjunction with Hannon's group to knock down individual members of a family of chromatin-associated proteins to develop new treatments for specific leukemia subtypes.

Vakoc and Hannon, in collaboration with James Bradner at the Dana-Farber Cancer Institute, have already made significant advances in this field by using RNAi screens to identify Brd4 — a member of the BET family of proteins that contains a distinct domain known as a bromodomain and helps regulate gene expression.

The group is already testing a drug candidate targeting Brd4 in clinical trials, Spector noted. "We want to capitalize on that initial discovery, and Chris now has a larger number of other exciting candidates, and we will work together with North Shore-LIJ to pursue that basic research as it moves from the laboratory to a more clinical opportunity," Spector added.

Another potential research program at CSHL that could benefit from access to North Shore-LIJ's large clinical cancer cohorts and clinical oncology expertise is work being done on pancreatic cancer in Dave Tuveson's lab. There, researchers are trying to identify blood-based biomarkers that could serve as early indicators of disease.

"One of the big issues with pancreatic cancer is once it's detected, it's pretty much too late," Spector said. Tuveson, he added, is using both proteomics and 3D culture systems as an alternative to mouse models in order to identify these potential new biomarkers. "He is able to take material from actual human pancreatic cancers, grow them in culture, and then treat them with various molecules to see if he can alter their gene expression profiles as a strategy to tailor treatment to a specific patient," Spector said.

Finally, Spector underscored his own research as a potential beneficiary of a clinical oncologist's perspective.

"We have a big focus on breast cancer, and we are trying to identify long non-coding RNAs that are upregulated in breast tumors versus normal mammary glands," he said. "The idea here would be to then develop approaches to modulate the expression level of those targets, so that we might be able to have an impact on both the primary tumor as well as on metastases."

Having a clinician's perspective on these types of basic research questions, Spector noted, might change the tack taken by CSHL researchers. "It's all about designing the experiment properly, and as basic scientists we have a particular view of how an experiment should be designed, but I think ... clinicians who know the disease really well and deal with patients on a daily basis ... may be able to provide additional insight to modulate the direction of that research, and put it on a slight tangent that will get us to a better end point," he said. "I think it's going to change the ultimate outcome of our approach to thinking about science, even in the early stages, as well as when we're ready to move them toward the clinic."

As part of their affiliation, CSHL and North Shore-LIJ have appointed an oversight committee with responsibility for oversight, staffing, and implementation. The committee includes three CSHL representatives — Spector; President and CEO Bruce Stillman, and Tuveson, who is also deputy director of CSHL's Cancer Center — and three representatives from North Shore-LIJ — Physician-in-Chief Lawrence Smith; Feinstein Institute for Medical Research President and CEO Kevin Tracey; and Chair of Medicine Thomas McGinn.