Two Teams Selected as Creativity Hubs Award Winners

The Office of the Vice Chancellor for Research is pleased to announce the winners of the 2022-2023 competitive funding for the Creativity Hubs Pilot Award: Development of a Novel Platform Approach to Expand the Degradable Proteome led by Lindsey James and the Systems Science Hub: Youth Mental Health co-led by Samantha Schilling and Paul Lanier.

Now in its sixth year, the Creativity Hubs program provides seed funding for researchers at UNC-Chapel Hill to explore new science with an emphasis on convergence, sustainability, innovation, and impact — all of which are exemplified in this year’s winning projects.

Investigator Team: Lindsey James, School of Pharmacy, PI; Michael Emanuele and Nicholas Brown, School of Medicine; Jon Collins, Office of the Vice Chancellor for Research (OVCR)

Small molecule-induced protein degradation is an emerging pharmacologic approach that is revolutionizing drug discovery. It creates a new ability to target a wide range of disease-causing proteins that cannot be targeted with traditional small molecules, paving the way for new drugs to be developed.

In this strategy, bifunctional molecules are designed to recruit a protein of interest to endogenous cellular degradation machinery, triggering destruction of the targeted protein. The limited number of E3 ligase ligands currently available to incorporate into bifunctional molecules is a major challenge to this new approach and additional strategies that can facilitate targeted protein degradation are needed to expand the degradable proteome.

“Targeted protein degradation is considered by many as a game-changing technology in drug discovery and there is a lot of excitement to see how targeted protein degraders fare in the clinic,” says principal investigator Lindsey James. “However, limitations exist that may prevent this technology from reaching its full potential. For example, there is a need to find new approaches to recruit E3 ligase complexes when the existing limited strategies are unsuccessful.”

The James Lab recently identified a novel E3 ligase recruitment strategy that has the potential to enable new access to important therapeutic targets. For the Creativity Hubs project, James has assembled a multidisciplinary team to build upon this discovery and develop a platform to rapidly demonstrate that the strategy has broad utility and can be applied to target a range of cancer-related proteins.

“I’m thrilled to have the opportunity to work with a fantastic group of UNC-Chapel Hill colleagues with an incredible amount of expertise in this area to transform our early findings into a more translational research program,” James says. “We hope to provide the drug discovery community with a new mode of protein degradation and catalyze the development of new therapeutics.”

Investigator Team: Samantha Schilling, School of Medicine, PI; Paul Lanier, School of Social Work, co-PI; Kirsten Hassmiller Lich, Michael Kosorok, and Mark Holmes, School of Public Health; Kori Flower, Stephanie Brennan, and Brianna Lombardi, School of Medicine

North Carolina has the highest prevalence in the nation of children living with an untreated mental health (MH) diagnosis. The COVID-19 pandemic exacerbated this crisis and exposed the ineffectiveness of the state’s MH system. Nationally, nearly one in five children have a MH disorder and suicide is currently the second-leading cause of death for children ages 10-17. Yet only 20% of these children ever receive treatment from a MH provider.

“As a primary care pediatrician, I’ve seen first-hand the mental health crisis affecting children in North Carolina. Youth mental health is one of the biggest public health problems we face and now is the time to act,” says co-PI Samantha Schilling. “Paul and I are well-positioned to take action along with an incredible team of scientists, mental health experts, and our critical partners.”

Leveraging existing data and deploying data science methods present an underutilized opportunity for improving the efficiency and effectiveness of a highly stressed and fragmented MH system.

In collaboration with the UNC School of Data Science and Society, this project will combine participatory methods and data science to build a complex simulation model of the system, and then apply machine learning methods to improve modeling efficiency and identify patterns from large administrative datasets.

The project will provide a platform for data scientists to work directly with policymakers, public health leaders, clinical providers, community members, and experts across scientific disciplines to design systems that improve the MH of children in the state.

The project is grounded in an ongoing partnership with NC Integrated Care for Kids (NC InCK) and is critical for gaining family, community, and stakeholder input and for translation of findings into real-time changes. The hub will also leverage regularly updated health system data available through the Sheps Center for Health Services Research in the form of health insurance enrollment and claims from NC Medicaid and Blue Cross Blue Shield of N.C. The use of system dynamics and data science has not been applied to the youth MH crisis to date, and this multidisciplinary team aims to leverage this innovation to create lasting impact.

“The Creativity Hubs award will be a gamechanger for our research team,” says co-PI Paul Lanier. “With this funding, we’ll have the resources needed to bring an amazing collaborative group together and apply our collective skills to this critical issue. We hope that the data will help us understand what has transpired with youth mental health services over the past few years and tell the story about how the system can better support families.”

About Creativity Hubs

The Creativity Hubs funding program was developed by OVCR to assemble teams of researchers from diverse disciplines to tackle major societal challenges and leverage additional support from external sponsors.

“The Creativity Hubs is the signature intramural funding program of OVCR and has served as an important catalyst for several major research projects at Carolina,” says Interim Vice Chancellor for Research Penny Gordon-Larsen. “These awards provide an engine for convergent projects that address some of the world’s greatest challenges through innovative approaches with tangible impact. I am so excited about this year’s projects, which promise to make inroads in two critical areas: development of a novel approach to the rapid discovery of new therapeutics; and use of a novel combination of system dynamics and data science methodologies to address the critical mental health issues facing our North Carolina pediatric population.”

To date, winning Creativity Hubs projects have stimulated exciting results and tens of millions in extramural funding. Through this award, both teams are eligible for $500,000 in continued funding to execute their project over the next two years.

Creativity Hubs awardees are guaranteed proposal development assistance from the Office of Research Development to pursue large-scale, follow-on awards that build from the program’s funding. The office also works with finalist teams that were not selected in each round to further develop their projects and connect them to other funding opportunities.