DEVELOPMENTAL AND REGENERATIVE BIOLOGY
Plikus developed an early interest in how whisker hairs in rats grow and regenerate after being surgically amputated. He then went on to receive his Ph.D. in Pathology from the University of Southern California (USC), doubling down on his fascination with hairs and studying how sweat glands in embryonic mouse skin can be turned into hairs with just one molecular “switch.” Through postdoctoral work at USC and the University of Pennsylvania, Plikus became more interested in regenerative biology of adult skin and the biomedical applications of tissue repair for better wound healing.

“What you realize is that regenerative biology and developmental biology are tightly intertwined,” said Plikus. “A lot of concepts from developmental biology have been readily translated into regenerative biology and regenerative medicine.”

Regenerative biology is deeply rooted in developmental biology, as growth and repair of tissues commonly tap into the same cellular and molecular ways of doing things. Through understanding the early mechanisms of tissue growth found in developmental biology, Plikus aims to unearth novel approaches to tissue regeneration.

In 2012, Plikus joined UCI as part of the university’s initiative to bolster stem cell research. The Plikus Laboratory for Developmental and Regenerative Biology, located at the Sue & Bill Gross Stem Cell Research Center, splits its focus between two areas of regeneration: enhancing wound healing and stimulating hair growth.

TEAMING UP TO LISTEN IN ON CELLS
The Plikus Lab benefits from the diverse array of colleagues across the university, and Plikus commends UCI on its interdisciplinary spirit in which individuals from different schools might collaborate on innovative projects.

“From a technical point of view, we are so well positioned to do some really complex and cutting-edge experiments due to an extremely interactive and collaborative faculty mindset that we have here,” said Plikus.

Plikus himself has been the beneficiary of a rewarding interdisciplinary project with Qing Nie, Ph.D., director of the NSF-Simons Center for Multiscale Cell Fate Research and Chancellor’s Professor at the School of Physical Sciences, School of Biological Sciences and the Henry Samueli School of Engineering.

While studying wound healing at the single-cell level, Plikus wished for a way to understand how various cells within the wound “talk” to one another to make collective decisions on the repair process. While such communication data was inherently encoded in the single-cell RNA sequencing they had done, there were no tools to parse that information into a legible format, especially for biologists.

Over the course of a few months, the Plikus team met with the Nie team to present a wish list of functions and usability from the perspective of a biologist. Then, Nie’s team wrote software to address those requests each week, which would eventually become CellChat, a one-of-a-kind tool for biologists to efficiently understand cell-to-cell communication within tissues.

More specifically, biologists can use CellChat to understand how individual cell types interact with each other as well as study each cell’s reactions to chemical compounds and pharmaceuticals. With this information, researchers can very quickly narrow down the list of candidate molecules that can target cells to elicit desired responses, such as enhancing wound healing or stimulating hair growth, as is the case with Plikus’ research.

Recently published in Nature Communications, CellChat was quickly adopted by biologists all over the world and has proven to be incredibly useful in the single-cell analysis space.

ENHANCING WOUND HEALING
In studying wound healing, Plikus spends a lot of time focused on skin and understanding the many forms of trauma it encounters in a lifetime, from physical injury, like blunt and sharp trauma, to DNA-damaging injury, like exposure to chemicals and radiation.

“The skin is a great model for looking at the mechanisms of regeneration,” said Plikus. “When the natural processes of healing work, they work great. But when they don’t, things can go bad very quickly, like diabetic foot ulcers, cancers, and so on.”

One example of the Plikus Lab’s ongoing research into wound healing centers on the differences between the way mice and humans naturally heal large wounds. According to Plikus, mice spontaneously regenerate new hairs and fat cells in large wounds with a high level of effectiveness. Humans, however, rarely exhibit such effective healing when it comes to large wounds. By studying how the processes differ, Plikus and team might one day make it easier for large wounds to heal more quickly in humans.

STIMULATING HAIR GROWTH
The Plikus Lab also looks to developmental biology when researching ways to stimulate hair growth following hair loss.

Contrary to what some might think, intact hair follicles still exist within the scalp skin in individuals experiencing hair loss — they’re simply dormant. If the proper signaling that tells inactive hair follicles to grow is supplied to skin, hair regrowth will soon follow.

Inspired by a congenital skin condition called a hairy nevus or more commonly a hairy birthmark, which is typically dark colored and covered in long hair, the team discovered, with the help of CellChat, a molecule that can prominently stimulate hair regrowth. With this technique, Plikus and team have identified several compounds that have translational potential for promoting hair growth for humans.

“A lot of discoveries were born from some rather unconventional observations,” said Plikus. “So my research is trying to look for what some might call weird biological phenomena to reverse engineer it, figure out the key molecules that drive it, and stimulate hair growth.”

Plikus then submitted a record of invention disclosure form to UCI Beall Applied Innovation’s Research Translation Group which assisted in filing a patent with the United States Patent and Trademark Office.

In 2018, Plikus received Proof of Product (POP) Grant funding to further develop the technology into a commercially viable product. Together with Dr. William Rassman, a world renowned hair transplant surgeon, as well as venture investor Spencer Segura, he formed the company Amplifica Inc., which in turn licensed the technology from UCI. Amplifica is currently conducting research & development to validate the compounds’ efficacy as well as safety. Amplifica’s preclinical results on their lead compound have shown significant early promise and its investors have committed to fund their FDA clinical trials.

Plikus is confident that his lab is on the cusp of discovering even more chemical compounds that can enhance wound healing and promote hair growth, which he plans to also commercialize.

INSPIRED INNOVATION
Plikus continues to inspire those around him through Applied Innovation’s Faculty Innovation Fellowship program. Through the fellowship, Plikus and other faculty in his cohort learn about the entrepreneurial resources available to them and become ambassadors for innovation at their schools.

“It’s inspiring to see faculty from other schools who have started companies,” said Plikus. “I try to take that excitement and on an individual level talk to faculty, especially junior faculty who often have good ideas but don’t know how to get started, and share a phone number or email to point them in the right direction.”