Amazing Science
Learning the Business of Science
NOAH WEISLEDER, PHD
AS A SCIENTIST and entrepreneur, Noah Weisleder knows the rewards and challenges of launching a high-tech business venture. He's co-founder and chief scientific officer of TRIM-edicine, an early-stage, privately held biotechnology company that is developing protein-based therapeutics. Between his work at TRIM-edicine and his ‘day job' as assistant professor of physiology and biophysics at Robert Wood Johnson Medical School (RWJMS), he's keeping pretty busy.
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"You learn a lot of useful things in grad school, but running a start-up business is not one of them," he observes.
Weisleder partnered with his postdoctoral mentor, Jianjie Ma, PhD, founder and president of TRIM-edicine and professor of physiology and biophysics at RWJMS, to develop this new company. Their most promising research focuses on MG53, a protein in the body that may have blockbuster potential because of its remarkable regenerative properties. MG53 is an essential component of the plasma membrane repair machinery in human cells. The researchers found that it has the properties of ‘cellular superglue,' targeting injuries and dramatically stimulating repair and healing. Repair of a cell's plasma membrane following injury or damage is an essential part of normal cell physiology. A breakdown of this process is observed in the progression of many different diseases affecting the heart, muscle, lungs, skin, brain and other organs.
"MG53 is found in the striated muscles of the body: primarily the skeletal and cardiac muscles," explains Weisleder. "We've found that it can be applied to other tissues to increase their regenerative capacity. We initially looked at it in diseases of the striated muscles — for instance, muscular dystrophy and heart failure — and found that after an injury, it will prevent cells from dying that normally would die from that injury, and restore the function of that tissue."
The researchers have taken their discovery a giant step further, finding that MG53 also has tremendous potential for treating a wide variety of diseases caused by disruption of cell membrane repair. "With collaborators we are using MG53 with other tissues, including the lung, and we've seen some remarkable effects," says Weisleder. MG53 is part of a larger gene family, the TRIM (tripartite motif) family of proteins — hence the name TRIM-edicine. The research team has cloned many members of this gene family (approximately 70) and begun to explore other members of the TRIM family that may have the same function as MG53 but are expressed in other tissues. "We're theorizing that a similar protein, say, from the brain, might have even greater regenerating capacities when applied to the brain."
Weisleder's interest in science kicked in at an early age, while he was growing up on a farm in northern Maine. "I know lots of scientists who got their start on farms," he says. "You really learn an appreciation for nature and its majesty. It stimulates your interest in science and how biological systems work together." Cleaning out his childhood bedroom two years ago, he dug out a pile of old school papers. At the bottom was one from kindergarten. "It asked what you wanted to be when you grew up," he recalls. "I wrote down either an astronaut or a chemist — but I spelled it cemist, without an h. I figured it out from there."
As a youngster, he launched his first research project one spring while listening to the sounds of the tree frogs Mainers call ‘peepers' because their mating call is a high-pitched peep. "The frequency is determined by the temperature," explains Weisleder. "The warmer it is, the faster they peep. They only start peeping when the temperature drops to a certain level. That's usually at night when it starts to cool off. I would count the peeps and graph them with the temperature."
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| MG53 IN SKIN CELLS |
He's come a long way since then, researching, teaching and running a startup company. In a typical week, Weisleder spends about twenty percent of his time at TRIM-edicine. It is managed as a virtual biotech model, meaning that the staff is small and each stage of scientific work is contracted out to research companies. "There are a lot of organizations out there specializing in every aspect of drug development," he says. "For example, you can hire a company to do your proof of concept animal testing. Once you get that data you take it to another company specializing in toxicology. A lot of the work I do with TRIM-edicine is managing our relationships with contractors." The company has also partnered with a few major pharmaceutical companies who are interested in MG53 for different indications and are doing their own testing on the protein.
The rest of his time is spent in the RWJMS lab, where he has three major research projects. One of them focuses on the effects of calcium signaling in muscle contraction and how disruption of normal calcium handling within the body leads to muscle diseases. Weisleder's interest in muscle tissue is not new. As a postdoctoral research fellow in Ma's lab, his studies focused on calcium regulation in both skeletal and cardiac muscle. This work continued when he moved to his own lab in 2008. "Calcium controls how much muscles contract and how much force they generate," he states. "Initially we thought that MG53 was involved in that process. But it turned out that it didn't really have much to do with that."
In March 2012, Weisleder received the prestigious 2011 Kaufmann Foundation Outstanding Postdoctoral Entrepreneur Award, which recognizes exceptional efforts in commercializing research conducted during a postdoctoral fellowship. "It was a thrill to get this award, which encourages postdocs to acquire the skills they need to become entrepreneurs," he says. "I didn't really expect it, because TRIM-edicine is a relatively young company and the product cycle for biotechs can be decades. I guess they liked our potential."
The company is currently working to raise enough money to launch clinical trials of MG53. "In our best-case scenario, three to five years to the marketplace is our goal now," he says. "Nine out of every ten biotech companies fail completely. One unsolvable problem can derail you. But so far, we've been fortunate and skillful in moving our company forward."
He adds, "There is
something special to this work,
when you see some of the results
we're getting with fairly
intractable diseases."
— Mary Ann Littell