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In Vivo

Translational Research


Drive to Boost Translational 
Research Gathers Speed


Eric A. Rose
Eric A. Rose
Sitting in his office in Milstein overlooking the Hudson River, Eric Rose, M.D., chairman of the Department of Surgery and world-renowned cardiac surgeon, doesn't look like a zealot eager to foment a revolution. But Dr. Rose is indeed at the forefront of a revolution – albeit a benign one whose goal is simply to bring new and better therapies to patients. The path to accomplish this, Dr. Rose believes, is through translational research, an approach that is becoming more and more fashionable at the NIH, HHMI, and other funding agencies and one that represents a significant departure from the way scientific research is usually undertaken at CUMC and most other academic medical centers.

InVivo sat down with CUMC's first dean for translational research to talk about the new push to make translational research a more integral part of the research endeavor.

What is translational research and why do you think it is the way to achieve better clinical results?

Translational Research Productivity - Chart

If we use new drugs approved by the FDA as a measure of clinical progress, the trend is going down."

ERIC ROSE

I have a simple definition of translational research: It's the bridge from discovery to delivery. It has a clinical goal or target in mind, which isn't the case for basic research.

Making observations in transgenic mice, for example, in and of itself, is not translational research.

People tend to think of translational research as a linear process starting with a discovery in the lab and then moving straight to the patient. Penicillin is a perfect example of how a discovery made in the lab to understand principles of biology is ultimately found to have tremendous use in combating illness.

But that path is opportunistic. If you do enough research something will eventually fall off the truck and help people. I don't think people realize it took decades to go from the initial discovery that the penicillium mold kills bacteria to the development of a useful drug.

I propose another translational pathway that begins not with a basic science discovery but in the clinic. This pathway identifies a problem in patients, takes that observation back to the lab, designs a solution, and then works through clinical trials and regulatory approval to deliver the solution to patients.

Unlike the traditional pathway, this process doesn't depend on luck and we can employ it for many different diseases. But it has to be fostered within academia and with collaborations among academia, government, and industry.

Why change? What's the problem?

We have a paradox in medicine today: there is abundant new scientific knowledge, and abundant funding [the NIH budget is now about $27 billion], but disappointing clinical progress. If we use new drugs approved by the FDA as a measure of productivity, the trend is going down [see graph]. Advances in biological sciences have been heralded as keys to unlocking cures to diseases like diabetes, heart failure, and Alzheimer's. The Human Genome Project, in particular, generated a lot of expectations. These cures have yet to happen, but in the long term they almost certainly will, if we change the way we do research.

How much translational research is already accomplished at Columbia?

Several groups here have already built translational research programs, in Alzheimer's, neurodegenerative diseases, and cellular therapies (see sidebar below).

There's a concern among some basic scientists that the new emphasis on translational research will detract from basic research. How would you respond to that?

I don't want to displace existing research strengths, but there is ample opportunity for our basic scientists to collaborate and do translational work. There may be some cultural shifts within the university because there is a school of thought that academic tenure should be based on research work that is novel mechanistically – that finds a new gene, or a new biochemical pathway. There should be increased focus on the potential impact of the research on patients, and I believe we're going to have to value that more in our academic culture.

How do you plan to promote translational research at CUMC?

My job is to serve as a catalyst to increase our translational research capabilities. I've now met with multiple investigators and there's lots of research we hope to accelerate. Frequently a solution to a problem comes from an outside group, so I'm trying to connect investigators and outside partners in government or industry. It's not just getting people to talk to each other, but getting them to work together.

—Susan Conova


Translational Research in Action

Andrew Marks


Andrew Marks and his team found the leak in a key channel in the heart that causes heart failure and cardiac arrhythmias – and the drug that fixes the leak.

As a basic scientist and a physician, Andrew Marks, M.D., chairman of the physiology department and a cardiologist, looks for ways to turn observations from the clinic or lab into new therapies for patients. That approach is responsible for a first-of-its-kind treatment for heart failure.

The research began with a clinical observation: The body's "fight or flight" nervous system is active at all times in heart failure patients – not just during times of stress – a condition that puts constant pressure on the heart. In the lab, Dr. Marks found that the constant stimulation of the heart alters the function of the calcium channel that controls the heartbeat and strength of contraction of the heart. In heart failure, the channel starts leaking calcium, which can weaken the heart's pumping action and sets up the potentially fatal arrhythmias that are responsible for half of all deaths from heart failure.



CUMC Receives $17.3 Million Grant for Translational
Heart Research

The NIH has chosen CUMC as one of five institutions nationwide to lead an intensive national research assault on congestive heart failure. Over the next five years, CUMC will receive $17.3 million to fund a Specialized Center of Clinically Oriented Research (SCCOR) program that focuses specifically on heart failure research. SCCOR programs are clinically oriented, collaborative, translational research programs. The SCCOR program at CUMC will look at the treatment of advanced heart disease from the perspectives of coagulation, infection and cell transplantation and myocardial recovery. Dr. Eric Rose is the principal investigator for the grant.

Dr. Marks' team of investigators – Xander Wehrens, Ph.D., Stephan Lehnart, M.D., Steven Reiken, Ph.D., and John Vest, M.D. – searched for ways to stop the leak. The drug they found, which has already been tested in people for another condition and found safe, slowed the leak and completely prevented arrhythmias in mice with leaky calcium channels.

Working with Donald Landry, Ph.D., professor of medicine, and his group of organic chemists the team then modified the drug to make it even more effective at plugging the leak. Dr. Marks is now creating a company to produce the drug and initiate clinical trials.

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