Developing Novel Treatments for Depression and Related Disorders

Developing Novel Treatments for Depression and Related Disorders

Delix Therapeutics, founded by David Olson, an assistant professor in the Department of Chemistry and the Department of Biochemistry and Molecular Medicine, is investigating whether neural plasticity–promoting drugs can lead to new treatments for depression, anxiety and related disorders.

Atrophy of neurons in the prefrontal cortex of the brain is known to play a key role in depression and related diseases. The known antidepressant properties of ketamine, a dissociative anesthetic, may stem from its ability to promote neural plasticity–enabling neurons in the prefrontal cortex to rewire their connections.

In 2018, Olson and his team demonstrated that a wide range of psychedelic drugs, including well-known compounds such as LSD and MDMA (commonly called Ecstasy), increase the number of neuronal branches, the density of small protrusions on these branches (dendritic spines) and the number of connections between neurons. Rats treated with a single dose of DMT (N,N-Dimethyltryptamine), a psychedelic compound found in Amazonian herbal tea known as ayahuasca, showed an increase in the number of dendritic spines, similar to that seen with ketamine treatment. Their work was published in the journal Cell Reports.

While drawbacks of using compounds such as LSD and MDMA as therapeutics include their hallucinogenic and psychostimulant effects, in a significant development Olson and his team discovered how to decouple the beneficial effects of neuroplasticity-promoting compounds from the unwanted hallucinogenic side effects.

This discovery could potentially open doors for the development of novel drugs to treat mood and anxiety disorders. Olson and his team have proposed the term psychoplastogen to describe this new class of “plasticity-promoting” compounds.

The company is investigating several distinct novel chemical scaffolds and molecules capable of promoting plasticity in order to develop safer and more effective alternatives to treat depression and related disorders.

Investigating a Better Therapeutic for Epilepsy

Syncanica Bio, a startup founded by Professor Mark Mascal

Syncanica Bio, a startup founded by Professor Mark Mascal with support from Ph.D. graduate Fei Chang, is investigating a synthetic cannabidiol (CBD) analogue as a novel therapeutic compound for conditions including anxiety, glaucoma and epilepsy.

Products containing CBD derived from cannabis or hemp plants have become popular for their potential health effects in part because CBD is less intoxicating than tetrahydrocannabinol (THC), the major psychoactive component found in marijuana.

Although the U.S. Food and Drug Administration in 2018 approved an oral CBD formulation for the treatment of some seizure conditions, CBD from extracts of cannabis or hemp poses legal problems in some states, as well as under federal law.

Mascal has developed an inexpensive synthetic alternative to CBD known as H2CBD—a molecule with a similar structure but made using commercially available compounds instead of extracts from hemp or cannabis.

H2CBD is non-intoxicating and easier to purify than the plant extract. It also eliminates the need to use agricultural land and irrigation for hemp or cannabis cultivation, avoids possible pesticide contamination and could circumvent the legal complications involved with cannabis-related extracts. Most importantly, unlike CBD, H2CBD cannot be converted to THC, eliminating the potential for abuse.

H2CBD was compared against herbal CBD in rats with induced seizures. H2CBD and CBD were found to be equally effective for the reduction of both the frequency and severity of the seizures. The work was published May 23, 2019, in the journal Scientific Reports.

Mascal is currently working with colleagues at the UC Davis School of Medicine to carry out additional studies in animals with the goal of moving into human clinical trials. UC Davis has applied for a provisional patent on anti-seizure use of H2CBD and its analogues.

Developing New Tools To Improve Food Production and Safety

Developing New Tools To Improve Food Production and Safety

The agriculture sector is facing an enormous task—to increase food production to support the planet’s explosive population growth. At the same time, the industry must address a growing number of food safety challenges associated with pathogenic bacteria like Salmonella and E. coli. These challenges are driving the need for and adoption of innovative solutions at the farm level, including remote sensing and robotics. However, utilizing these new technologies effectively requires the ability to clearly interpret and analyze the vast quantities of data being collected, which comes with its own set of challenges.

AgriNerds, one of 14 startups enabled in FY 2018­–19 by technology developed at UC Davis, is helping farmers harness the power of these technologies by providing a data management and visualization tool to integrate and interpret this information in real time. Their Web-based application uses both machine learning and decision sciences to help farmers optimize production yield, food safety and operational efficiency.

The technology is based on the work of Maurice Pitesky from the UC Davis School of Veterinary Medicine-Cooperative Extension and former students Roberto Carrasco, Joseph Gendreau and Tristan Bond.

The team received proof-of-concept funding from the UC Davis Data, Informatics and Application Launch (DIAL™) Grant program from the Office of Research to develop and test the initial versions of the product. The startup is working with several poultry companies to further optimize their custom machine learning ­algorithms in order to expand operations throughout the agricultural sector.

Pioneering a New Coffee Industry in California

Juan Medrano and Marta Matvienko

Juan Medrano, co-founder, and Marta Matvienko, lab operations and bioinformatics, breed coffee plants suitable for growth in California at the UC Davis-HM.CLAUSE Life Science Innovation Center in Davis, California.

In 2017, geneticists from UC Davis sequenced the genome of Coffea arabica —a species responsible for 70% of global coffee production—with the goal of developing new high-yielding and high-quality varieties adapted to the stresses caused by climate change.

Progress from the research enabled the formation of a new company, Frinj Coffee, founded by Jay Ruskey, a farmer, and Juan Medrano, a professor and geneticist from the UC Davis College of Agricultural and Environmental Sciences, along with Andy Mullins and Lindsey Mesta. The company is pioneering the coffee growing industry in California, well outside the traditional tropical geographic belt closer to the equator.

In 2018, Frinj Coffee joined the UC Davis-HM.CLAUSE Life Science Innovation Center—part of Venture Catalyst’s DRIVE network of incubators—to further develop novel coffee varietals that are adapted to grow within the specific soil and climate conditions of the state.

Frinj Coffee is providing coffee plants, consulting and post-harvest resources to over 40 new farms across Southern California—and has marketed coffee through Oakland-based roaster Blue Bottle Coffee, San Diego–based Bird Rock and premium international buyers.

14 New Startups Emerge From UC Davis Innovations

4 New Startups Emerge From UC Davis Innovations

Technologies developed at the University of California, Davis, enabled the foundation of 14 startup companies during the fiscal year ending June 30, 2019.

“Research universities like UC Davis are a key source of vital innovation for numerous industries,” said Prasant Mohapatra, vice chancellor for research at UC Davis. “These startups are undertaking the important first steps in developing and refining the commercial potential of their inventions. It’s exciting to see such a wide range of entrepreneurial undertakings based on our campus innovations.”

Several of the startups are focused on technology solutions addressing important societal needs, including data management for the agriculture industry, software for fraud prevention, and distributed and immutable ledger technology for vital records such as birth certificates.

Many are developing potential solutions to address serious health challenges.

Delix Therapeutics, founded by David Olson, an assistant professor in the Department of Chemistry and the Department of Biochemistry and Molecular Medicine, is an example of such a company. It is investigating whether neural plasticity-promoting drugs could lead to new treatments for depression, anxiety and related disorders without the unwanted hallucinogenic effects of such molecules.

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Neurologic Disease Research at UC Davis Contributes to First Treatment Specifically Approved for Postpartum Depression

Michael Rogawski conducted lab and clinical research on the neuro-steroid

Dorota Zolkowska and Michael Rogawski. Michael Rogawski, a professor in the UC Davis Department of Neurology, and Dorota Zolkowska, a project scientist in Rogawski’s research laboratory, conducted studies resulting in inventions related to allopregnanolone as a potential treatment for neurological diseases.

Dorota Zolkowska and Michael Rogawski. Michael Rogawski, a professor in the UC Davis Department of Neurology, and Dorota Zolkowska, a project scientist in Rogawski’s research laboratory, conducted studies resulting in inventions related to allopregnanolone as a potential treatment for neurological diseases. (Rudy Meyers Photography)

Original post: research.ucdavis.edu/ucdavis_sage_therapeutics

(SACRAMENTO) — Sage Therapeutics announced March 19 the U.S. Food and Drug Administration’s approval of its product, Zulresso™ (brexanolone) injection, for the treatment of postpartum depression in women. Initial development of an intravenous formulation of allopregnanolone (also known as brexanolone) and first-in-human clinical studies were conducted by Michael Rogawski, a professor in the UC Davis Departments of Neurology and Pharmacology. Rogawski is former chair of the Department of Neurology.

In laboratory-based and clinical research, Rogawski and his colleagues investigated the neuroactive steroid allopregnanolone as a potential therapeutic agent for neurological diseases. The University of California granted rights to Sage Therapeutics, including licenses to certain patent rights, for the commercial use of allopregnanolone.

This is the first drug approved by the FDA specifically for postpartum depression. Postpartum depression is the most common medical complication of childbirth and affects approximately one in nine women who have given birth in the U.S.

“It’s very exciting to see the development of this treatment reach such a significant milestone, offering new hope to those affected by postpartum depression,” said Prasant Mohapatra, vice chancellor for research at UC Davis. “This is a wonderful example illustrating the role UC Davis research plays in helping to address needs around world.”

Neuro-steroid a good candidate for post-partum depression treatment

Allopregnanolone is a naturally occurring neuroactive steroid derived from the female sex hormone progesterone. Rogawski became interested in allopregnanolone as a potential treatment for postpartum depression because studies with neuroactive steroids conducted in his and other laboratories showed antidepressant potential.

“Blood levels of progesterone, and therefore allopregnanolone, rise dramatically as pregnancy progresses, but begin to decrease in late pregnancy and then fall precipitously during the day or two after giving birth,” said Rogawski. “I reasoned that allopregnanolone levels might also fall and I hypothesized that the withdrawal of this endogenous antidepressant substance could trigger depression for some women. This led to the discovery of allopregnanolone as a treatment for postpartum depression.”

“From my very first engagement with Sage Therapeutics several years ago, the commitment of the company’s principals to work with the university to enable the development and commercialization of this important discovery was evident,” said Dushyant Pathak, UC Davis associate vice chancellor for research and executive director of Venture Catalyst. “At the university, we reciprocated through creative and goal-oriented approaches to structuring patent, data and material transfer agreements to support Sage’s development of this much-needed treatment.”

In addition to licensed patent rights, Sage Therapeutics was granted a right of reference to the University of California’s Investigational New Drug (IND) application package related to the use of allopregnanolone, which facilitated Sage’s transition of allopregnanolone into the clinic. The university also made allopregnanolone drug substance available for Sage’s use in early clinical trials.

“Up until the development of brexanolone, there was no specific treatment for postpartum depression. I am extremely pleased that our research has led to a rapidly acting treatment for this all-too-common condition,” said Rogawski.

About postpartum depression

Postpartum depression is a distinct and readily identified major depressive disorder that may have devastating consequences for a woman and for her family, which may include significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, motor challenges, lack of concentration, loss of energy and poor self-esteem. In developed countries, suicide is the leading cause of maternal death following childbirth. Postpartum depression affects approximately one in nine women who have given birth in the U.S. and 400,000 women annually. More than half of these cases may go undiagnosed without proper screening.

Rogawski and UC Davis project scientist Dorota Zolkowska are the inventors of U.S. Patent No. 10,251,894 B2, issued to the Regents of the University of California on April 9, 2019, and claiming methods of treating post-partum depression.

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Record Number of UC Davis Startups for 2017–18

ara Ann Niendam, an associate professor in residence and the executive director of the UC Davis Early Psychosis Programs, and Laura Tully, an assistant professor of psychiatry, are the co-founders of Safari Health, a digital health technology company focused on evidence-based care for young people experiencing serious mental illness.

Tara Ann Niendam, an associate professor in residence and the executive director of the UC Davis Early Psychosis Programs, and Laura Tully, an assistant professor of psychiatry, are the co-founders of Safari Health, a digital health technology company focused on evidence-based care for young people experiencing serious mental illness. (Lisa Howard/UC Davis)

Original post: research.ucdavis.edu/record-number-of-uc-davis-startups-for-2017-18

The University of California, Davis, enabled the foundation of 16 commercial companies during the fiscal year ending June 30, an all-time high for the university. This brings the total number of startups made possible by UC Davis technologies during the past 10 years to 137.

“Our commitment to supporting innovative faculty, students and staff — with the coordinated suite of resources we offer through Venture Catalyst — is accelerating societal benefit and regional economic impact through a robust pipeline of university spinoffs,” said Dushyant Pathak, associate vice chancellor of research and executive director of UC Davis Venture Catalyst.

“Not only are we seeing an uptick in the number of exciting new technology ventures from the university, but we are also seeing the achievement of significant commercialization milestones by prior years’ startups,” Pathak said.

Many of the startups are targeting unmet needs in human health, with new tests, technology platforms and therapeutics for diagnosing, monitoring and treating a wide variety of conditions and diseases.

Four of the new companies have innovations focused on cancer. Others are developing therapeutics aimed at treating obesity, multiple sclerosis, Alzheimer’s disease and optic neuropathy.

Safari Health, co-founded by Laura Tully, an assistant professor of psychiatry, and Tara Ann Niendam, an associate professor in residence and the executive director of the UC Davis Early Psychosis Programs, is a digital health technology company focused on evidence-based care for young people experiencing serious mental illness. The company’s first product, Mobi, is an app-based technology for psychosis clinics to monitor how patients are faring in between caregiver visits.

“In a traditional mental health treatment setting, patients can often go weeks in between seeing a therapist or doctor,” said Tully. “A lot can happen in that time. Mobi closes that loop and allows the provider to monitor how things are going. If there is something predictive of a bad outcome, the provider is notified and can make a care decision.”

“We are using technology to get data in order to improve care,” said Niendam. “With this platform we can connect people to appropriate care and also improve the care that’s provided.”

Petr Janata, a professor in the Department of Psychology and a faculty member in the UC Davis Center for Mind and Brain, is developing a different type of software platform — one that lets people preserve and share memories and stories associated with specific music.

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Startup Founded by Researchers From UC Davis and UC Berkeley Acquired by TDK Corporation

Chirp Microsystems

By Lisa Howard

Chirp Microsystems, a startup enabled with technology developed at UC Davis and UC Berkeley, announced it has been acquired by Japanese electronics giant TDK Corporation.

Based in Berkeley, Chirp Microsystems makes tiny, ultra-low power sensors that function like sonar or echolocation, sending out ultrasonic sound waves and then measuring how long it takes for the returning echo to come back. The micro-electromechanical systems (MEMS) technology enables extremely precise sensing, ranging from several centimeters to several meters.

Chirp’s sensor technology can be used in drones, robots, vehicles, smart home products, augmented reality and virtual reality systems, and many other applications. Because the transducers are just a few millimeters across, they use very little power compared to a conventional ultrasound transducer.

Chirp was one of 13 companies enabled by UC Davis research during fiscal year 2014–15. The company licensed intellectual property from the University of California and currently owns over 20 patents covering the core MEMS device technology, application specific Integrated Circuits (ASIC) design, packaging, signal processing, ultrasound systems, and applications.

David Horsley, a professor in the UC Davis Department of Mechanical and Aerospace Engineering, is a co-founder of Chirp and the chief technology officer.

“Professor Horsley is an exemplar of the type of faculty entrepreneur who is driving societal impact through innovation in the collaborative environment that the University of California fosters, and that the UC Davis College of Engineering enables,” said Dushyant Pathak, associate vice chancellor of research and executive director of Venture Catalyst. “The novel sensor system that he invented and that was developed by Chirp Microsystems, where he was co-founder and chief technology officer, is an example of the cutting-edge technology and engineering innovation being driven by our faculty.”

David Horsley, co-founder of Chirp Microsystems and a professor of electrical and computer engineering at the University of California, Davis, explains the technology behind Chirp’s sensors at CES 2016. (Credit: National Science Foundation)

Horsley and his graduate students developed the sensor technology collaboratively with Bernhard Boser, a professor in the UC Berkeley Department of Electrical Engineering and Computer Sciences. Much of the work was done at the Berkeley Sensor and Actuator Center, which conducts industry-relevant, interdisciplinary research on micro- and nano-scale sensors.

“UC research projects like ours fill an important role of conducting fundamental research that can have commercial impact,” Horsley said. “After the fundamental work was done, we founded Chirp based on a vision of tiny ultrasonic sensors in everyday devices, from smart-phones to robots. As part of TDK, Chirp will have the resources and global scale to make this vision a reality.”

The acquisition announcement from TDK highlighted Chirp’s synergies with TDK sensors and sensor fusion software libraries. TDK also noted the uniqueness of Chirp’s sensors: “Chirp’s ultrasonic sensors are robust, accurate, draw less power and are smaller than the ultrasonic range finders used in today’’s automotive applications and industrial solutions,” the company said in their statement.

Chirp will become a fourth business unit, Ultrasonic Tracking and RangeFinding, within InvenSense, a TDK Group company headquartered in San Jose. InvenSense is a world leading provider of MEMS sensor platforms. Chirp will remain based in Berkeley.

About Chirp Microsystems
Chirp Microsystems mission is to bring ultrasonic sensing to everyday products. Founded in 2013 based on pioneering research performed at the University of California, Chirp’s piezoelectric MEMS ultrasonic transducers offer long range and low power sensing capabilities in a micro-scale package, enabling products to accurately perceive absolute position in the three-dimensional world in which we live. Combined with Chirp’s embedded software library, these sensors advance user experiences with VR/AR, mobile, wearables, robotics, drones and occupancy detection.

About UC Davis
UC Davis is a global community of individuals united to better humanity and our natural world while seeking solutions to some of our most pressing challenges. Located near the California state capital, UC Davis has more than 35,000 students, an annual research budget of over $780 million and a comprehensive health system. The university offers 102 undergraduate majors and 99 graduate programs through four colleges and six professional schools.

About Venture Catalyst
Venture Catalyst is one of three units within the Technology Management & Corporate Relations division of the UC Davis Office of Research. Venture Catalyst furthers the university’s educational, research and public mission by supporting UC Davis students, faculty and researchers in translating science, engineering and innovative research, through well-resourced startups, into societal impact.

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Collaboration between UC Davis Foods for Health and Company Spin-off Evolve BioSystems Identifies Detrimental Generational Change in Gut Bacteria of Infants

Collaboration between UC Davis Foods for Health and Company Spin-off Evolve BioSystems Identifies Detrimental Generational Change in Gut Bacteria of Infants

Evolve BioSystems, Inc., a spin-off from the UC Davis Foods for Health Institute (FFHI) that is developing novel solutions to restore and maintain a healthy newborn gut microbiome, announced findings from new research that connects elevated infant fecal pH levels to a change in the infant gut microbiome. Their release states that over the past 100 years, the average pH of a baby’s stool, which can indicate the type of bacteria in the baby’s gut, has undergone an alarming increase from pH 5.0 to 6.5. The study, published in the American Society for Microbiology journal mSphere, connects this rise in pH to a generational loss of Bifidobacterium, a critical gut bacteria during infancy, and an accompanying increase in a number of harmful bacteria.

The team reviewed 14 clinical studies published between 1926 and 2017, identifying a change in pH from 5.0 to 6.5 over this time period. The authors attributed this trend to an observed reduction of Bifidobacterium in the infant gut, along with an increase in potentially harmful bacteria such as E. coli and Clostridia, resulting in “dysbiosis”, a potentially detrimental imbalance of the gut microbial ecosystem.

Evolve’s founding team, which includes UC Davis faculty members Bruce German, David Mills, Carlito Lebrilla and Daniela Barile, along with former FFHI Assistant Director Samara Freeman, has been conducting research at the forefront of infant nutritional health for over a decade, focusing on the key role that breast milk plays in creating a healthy intestinal tract.

The full release can be found here.

UC Davis Startup Receives FDA Clearance for Polymer That Can Help Injured Bones Regrow

Charles Lee

Charles Lee, the founder of Molecular Matrix Inc., is a stem cell biologist and an assistant adjunct professor at the UC Davis School of Medicine. Molecular Matrix has received Food and Drug Administration clearance for a synthetic bone void filler, Osteo-P, that can help injured bones regrow. (Gregory Urquiaga, UC Davis)

By Lisa Howard

A biotechnology startup enabled by UC Davis, Molecular Matrix Inc., has received Food and Drug Administration clearance for a carbohydrate-based polymer that can help injured bones heal and regrow.

Osteo-P™, a synthetic bone graft substitute, supports and guides the growth of new bone — such as when there is a loss of bone due to injury or surgery — after which the biomaterial is resorbed and replaced with the patients’ own bone during the healing process. With the 510(k) FDA clearance, Molecular Matrix will now be able to take Osteo-P to market.

“This is yet another meaningful milestone for UC Davis and our technology commercialization efforts,” said Dushyant Pathak, associate vice chancellor of Technology Management and Corporate Relations, and executive director of Venture Catalyst at UC Davis. “Our focus on innovation and technology commercialization is a direct reflection of its being one of the most tangible ways in which the university can fulfil its mission of public benefit and societal impact.”

For Charles Lee, the founder of Molecular Matrix and also an assistant adjunct professor in the Department of Cell Biology and Human Anatomy at the UC Davis School of Medicine, the FDA clearance marks an exciting turning point for the company UC Davis helped him found in 2011.

“What began as an idea from UC Davis has reached all the way to FDA clearance,” Lee said.

Lee received his B.S. in microbiology and Ph.D. in comparative pathology and did his postdoctoral work at UC Davis. He became fascinated by stem cells as an undergraduate when he had an internship with Alice Tarantal, professor of pediatrics and cell biology and human anatomy in the UC Davis School of Medicine, and the associate director of the UC Davis School of Medicine Stem Cell Program.

Tarantal gave him a line of stem cells to culture.

“I fell in love with those cells,” Lee said. “That’s how I got into stem cell biology. There was nothing else I wanted to do than study and research them.”

The stem cells he worked with were grown in a single layer, but Lee began thinking about new ways to grow them.

“Stem cells behave much differently when they are grown in an aggregate as opposed to a monolayer,” he said. “But building up stem cells is not easy. It requires a scaffold — a matrix or structure — to help support the cells to grow into an organoid.”

Stem cell substrates did exist, but Lee said none was ideal. “I specifically wanted to use a carbohydrate, a sugar, for scaffolding. I wanted it to be degradable and nontoxic, to not affect stem cells in any way,” Lee said.

The invention he came up with, a hyper-crosslinked carbohydrate polymer technology, provides a platform for stem cells to grow both in vitro and in vivo. Lee explained that the platform is all about cross-linking.

“We chemically crosslink the carbohydrate molecules to build a massive structure. It’s crosslinked so much that it can hold its shape under heat and pressure.”

Helping bones regrow

For its first clinical launch, Molecular Matrix focused on creating a polymer product to help bones regrow without stem cell transplantation.

“Bone is a good place to start,” Lee said. “It is simpler to regenerate than other organic systems.” The polymer platform has potential to be used for other clinical and research applications. “Cartilage or heart tissue, for example,” Lee said.

In its unprocessed form, Osteo-P is spongy and porous and can be made in a variety of shapes and sizes. Lee explained that the unique composition of Osteo-P creates an optimal microenvironment for bone precursors such as osteoblasts, leading to the formation of healthy bone.

“The need for bone substitute products is expected to expand,” said Jim Keefer, COO of Molecular Matrix. “The global bone graft and substitutes market was estimated at $2.1 billion in 2013 and is expected to grow to $2.7 billion by 2020.”

The company plans to release the product for single-patient use possibly as early as mid-March. It will be available as large pore granules, sheets, cubes, wedges and cylinders or in custom sizes.

Lee credits the Technology Management and Corporate Relations unit at UC Davis as being essential to Molecular Matrix’s success, helping him navigate the dual roles of innovative researcher and entrepreneur. TMCR provided support for everything from patent processing to incorporation to networking to helping him raise capital.

Starting out, Lee thought he would need to focus primarily on raising capital to grow his startup, but focusing on people turned out to be his best investment.

“I ended up getting more and more people who believed in the technology, and when the people came together, the money followed,” Lee said. “Jim Keefer, our COO, was instrumental in getting broader interest in the company.”

“What is most heartening about how Charles has grown and developed Molecular Matrix is his engagement of UC Davis students as interns and employees within the company,” said Pathak. “Charles could have set up the company anywhere, but he chose to build and grow it in proximity to UC Davis, thereby benefiting from close access to university resources, including Venture Catalyst, while contributing to regional economic impact. Charles’ recognition of the talent pool that UC Davis represents is no small driver of the company’s success.”

Despite the challenges of juggling many roles, Lee never once considered letting another company commercialize the scaffolding technology he developed.

“We scientists have fun developing projects, ideas and concepts into something that can ultimately help patients,” Lee said. “I can’t imagine stopping in the middle and having someone else have all the fun. I want to take it all the way — from benchtop to bedside.”

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