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Innovative Academics to Work Elbow-to-Elbow with Big Pharma

Wed, 02/05/2014 - 9:47am
Cynthia Fox, Science Editor

The new $650 million Belfer Research Building at the Weill Cornell Medical College aims to shake up academia with a new interdisciplinary approach. It not only boasts different “research hubs” from Weill Cornell and other academic institutions working side-by-side, engaging in novel cross-talk, inspiring new ideas. But it also has an entire floor where academics and industry work elbow-to-elbow.

With funds from both government and private sources like Bill Gates, the goal is to speed translational research via unconventional partnerships. Department of Microbiology and Immunology Chairman Carl Nathan says the intent is to enable interdisciplinary integration both “vertically and horizontally.”

For instance, the building is about “form fitting function” in two ways, he says. Physically it is energy efficient to maximize natural light. Figuratively, the building will “channel human energy into productive encounters across departments, diseases, and basic and clinical scientists.”

In a recent tour given to Drug Discovery, Nathan noted the research hubs are separated by glass doors, so people can see each other’s work. Labs spill into communal coffee areas. A two-story garden will lure scientists into spontaneous interdisciplinary strolls. The new dean, Laurie Glimcher, wants to snap open “research silos” that keep scientists isolated, he says.

Glimcher has emphasized a “bench/bedside/bench” mentality. When clinical work needs tweaking, it can be popped back to the lab for modification ASAP.

Nathan noted that one pride and joy is the top floor, which houses the Tri-I TDI (Tri-Institutional Therapeutics Discovery Institute). There, academics from Weill Cornell, Memorial Sloan Kettering, and Rockefeller University will work with Big Pharma. It is lined with more tools of chemistry than biology. “This floor will close the Valley of Death,” he says. “Often in academia, our work had an ivory tower quality. We said, ‘Our research might deliver cures, but we don’t know because we haven’t tested it in people or animals. Without medicinal chemistry, we’ll put it out there, and hope a company develops it.’ This was wasteful. The academics put out potential products with such inferior properties companies had to start over— and not well, without biology expertise. There was a lot of talking past each other.”

The Belfer Research Building features 13 floors of laboratories equipped with the most advanced research technology. (Source: Weill Cornell Medical School/Jeff Goldberg, Esto for Ennead Architects)But at the Tri-I TDI, “academics will work with pharmaceutical experts from the earliest moments. Both sides will learn enough of each other’s language they can anticipate what is meaningful to both. Tri-I imports drug company medicinal chemists. People from Takeda will live here for one to five years. They will work with us on projects submitted by scientists at all three institutions,” Nathan says.

That interdisciplinary energy is bi-directional—and trans-continental. One of Nathan’s post-docs just returned from the Tres Cantos Open Lab Foundation in Spain, where Glaxo Smith Kline staff teach academics their ways. “My post-doc came back after a year with a compound she discovered using our assay, which they let us set up in their facility. A second post-doc is also back with compounds. It is very different. We are excited. We think this will break the logjam slowing drug discovery to a trickle.”

Nathan will be the most visible embodiment of all the interdisciplinary work. He works on tuberculosis (TB) research— in part with Bill Gates academic/industrial accelerator funds— in the basement’s new BSL 3 lab. But he is also a founder--and board of directors member--of Tri-I TDI (which is helmed by Michael Foley, former chief of the Broad Institute's Chemical Biology Program). One of Nathan's chemists has already devised a potential project for the Tri-I TDI. In trying to prove certain inhibitors were selective for TB, so they would not harm the host, “[the chemist] discovered versions of his inhibitors that do inhibit a target in the host— that everybody’s been trying to inhibit for years as a treatment for autoimmune inflammatory disease. It was classic serendipity. The target is the immuno-proteosome. We had no idea we would make an immune-proteosome inhibitor more selective for the human immune-proteosome than has ever been reported.”

If the inhibitor is accepted by the Tri-I TDI, aspects of drug development normally handled later by Big Pharma— solubility, safety, arrhythmia-avoidance— will start immediately. “This is the kind of medicinal chemistry we normally do not do systematically,” Nathan says. Takeda will bring Weill Cornell the Big Pharma expertise of “computational chemists, molecular modelers, pharmacologists, toxicologists, etc.” Takeda people will “be inventors with us,” but Weill Cornell will own the intellectual property. Takeda will have rights of first look. “They also will be able to see how we think, which is their primary reasoning. They want to learn the innovation culture. Many companies do.”

The complex has attracted new academic stars like Lewis Cantley. Brought from Harvard University, Cantley discovered the signaling pathway phosphoinositide 3-kinase (PI3K), work oft mentioned as Nobel Prize-worthy. Cantley is the new head of the cancer center. Cantley notes his staffers will choose two programs, one in disease and one in basic science or population, “so clinicians can learn from basic science, and researchers can sense whether their work is relevant to the clinic.”

The bench/bedside/bench aspect is key, Cantley says. There are over 20 PI3k anti-cancer inhibitors. Some patients can go temporarily insulin- resistant on them. “These patients must be managed with metformin or insulin. But if the tumor has insulin receptors on it, this can reactivate tumors. We are designing a trial to tease out whom to give insulin, or Metformin, or higher doses of PI3K. We are making preclinical models, determining biomarkers. We went from bench to bedside— which told us to go back to the bench.”

Cardiologist James Min, another star hire, will head an interdisciplinary team at the Dalio Insitute of Cardiovascular Imaging to marry advanced imaging with other diagnostics. His team will investigate sophisticated questions such as what density of artery calcium is dangerous, and what density is protective. (See related Bioscience Technology story.) Cutting edge CT scan calcium scoring— which top researchers believe best predicts heart disease— will be offered to all patients. He will use the bench/bedside/bench approach. “Our team will push forward rapidly.”


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