Dear Colleagues,

This April 2023 issue of the research newsletter recognizes the recent awarding of successful grant applications to several of our researchers, with particular congratulations to Dr. Kristin Schreiber on the five-year renewal of her NIH R35 grant. We will have a strong showing at the 55th annual SOAP meeting with many abstracts to be presented at the conference in New Orleans early in May. There is an interview with Dr. Jeff Karp, with a particular focus on his recent work targeting stem-cell proliferation in order to reverse hearing loss.

Please note that the final deadline to submit medically challenging cases and quality improvement projects to this fall’s annual ASA meeting in San Francisco is nearly here. Medically challenging cases are particularly a good category for residents to submit. The deadline is May 17th.

Chris Connor

Dr. Karp is a chemical engineer from Canada, who grew up in a small town about an hour and a half northeast of Toronto called Peterborough. He grew up in the countryside when he moved out there with his parents and sister in the 3rd grade. This led to all the great exposure nature has to offer. He had a farmer’s field in his backyard, a sheep farm on one side, and a buffalo farm across the road. There was a creek that ran under bridge on his driveway. He recalls waking up in the middle of the night to a pack of wolves in the front yard heading over to the sheep farm. Dr. Karp went to McGill University where he studied chemical engineering. He was there for 5 years, initially registering in biology before transferring to chemical engineering in his 2nd year. He stayed an extra year to take physiology and biomedical engineering courses. Next, he went to the University of Toronto for his Ph.D. in Chemical and Biomedical Engineering. After that he joined Dr. Bob Langer’s lab at MIT for 3 years for post-doctoral work. Finally joining the Brigham in July of 2007.

Dr. Karp has always been interested in science, but school posed a lot of challenges for him as he was diagnosed with learning differences including ADHD imposing significant struggles in his curriculum. Dr. Karp loved everything science and was really fascinated by what he could learn. “In the 7th grade I had an incredible science teacher who was very inspirational. That’s when I got really excited about it,” says, Dr. Karp. He did have his fair share of teachers who didn’t believe in him, but the ones who did were inspirational and saw the potential he had and helped guide him to realize it.

His Ph.D. research in Toronto was in the area of bone engineering where he spent 5 years. He did his Post-doc at MIT and focused for the first year on advancing his bone engineering work to keep it safe and maximize potential for a publication. During his 2nd year he wanted to step outside the box and only work on things that he had never worked on before. He began synthesizing new degradable polymers for biomaterial applications. He also began developing microscale devices for diagnostic applications and for analyzing the biology of stem cells. In 2007, before his faculty position began, at the tail end of his post-doc he began developing new bio-inspired medical adhesive glues and tapes that were intended to attach to tissue to seal them in place of staples or sutures. He built upon this after starting his faculty position and continued to turn to nature for inspiration to help solve medical problems.

Dr. Karp and his colleagues recently had a breakthrough in reversing of hearing loss. “The hearing regeneration work began in the intestine while trying to understand how the lining of the intestine perfectly regenerates every 4 or 5 days,” says Dr. Karp. The stem cell responsible for this incredible regenerative capacity had been identified by a research group in the Netherlands. Karp and team began trying to understand how to control this stem cell with standard drugs like small molecules, but as many know stem cell therapy is complicated due to the need of having to take cells out of the body, manipulate them, and put them back in the body. Transplanted cells respond and behave differently in different areas of the body adding to the complexity of achieving a predictable homogeneous response. Therefore, the question that arose was “could we simplify the approach by being able to deliver small molecules into the body and target the stem cells or progenitor cells in-situ without needing to isolate, manipulate or deliver cells” Dr. Karp says. They started in the intestine and discovered two small molecules that could replicate key signaling in the micro-environment of the stem cells. This enabled control of the division of the stem cells while maintaining their stem cell state and generated substantial excitement.

Rather than keep advancing the discovery in incremental ways, Dr. Karp and his colleagues asked themselves “is there something that we can do with this new information and insights that would be just as exciting or even more than what we had just done.” Dr. Karp describes. They found a paper demonstrating that the progenitor cells of the inner ear had similar properties of the progenitor cells lining the epithelium of the intestine, including a cell surface receptor called LGR-5. Unlike the stem cells in the intestine which keep diving throughout life, in the inner ear these progenitor cells don’t divide after birth and remain dormant. This led them to the question “Might the small molecules discovered in the intestine model work on the progenitor cells in the inner ear?” The answer was yes. They found a 2000-fold greater level of proliferation. This catalyzed the formation of Frequency Therapeutics, a biotechnology company co-founded by Karp, Bob Langer, and others, and the advancement of the work into clinical trials. One of the ongoing trials will have a readout during the first few months of 2023.

In the future Dr. Karp is interested in developing technologies for oral delivery of biologics. Specifically, to orally deliver in the form of pills or capsules proteins, nucleic acids, and peptide-based drugs. He and his collaborators are currently in the process of developing a number of bio-inspired prototypes.  Dr. Karp is also advancing a new platform to achieve a more targeted way to deliver drugs to the brain and a new immune stimulating methodology to treat cancer.

Dr. Karp and his wife started African Drumming the past several months and take lessons together. Dr. Karp has two children. His son is 17 years old and plays quarterback at Brookline High and his daughter is 14 years old plays volleyball, basketball, and is an avid dancer. His wife owns a Pilates studio in Coolidge corner. In Dr. Karp’s free time outside of work and family he likes to spend time meeting with friends and colleagues for lunch and coffee to bring fresh energy to his life. He loves being exposed to different perspectives and the energy transfer between humans and non-human beings (namely his 2 dogs). Finally, Dr. Karp is an amazing scientist who has done two TED Talks, cofounded numerous companies, and several honors and awards.

Follow the link below to see more of Dr. Karp’s work:

Insights from the Lab Lead to a New Approach to Reversing Hearing Loss - Brigham Clinical & Research News