N.C. A&T Distinguished Professor’s Biomedical Research Garners Collaboration, Support

EAST GREENSBORO, N.C. (May 7, 2025) – Robert H. Newman, Ph.D., Nathan F. Simms Distinguished Professor in the Department of Biology at North Carolina Agricultural and Technical State University, is uncovering new modes of protein kinase regulation involved in health and disease, building collaborations with academic and industry partners, and creating exciting opportunities for students to engage in cutting-edge biomedical research.

National Institutes of Health

Newman was recently awarded a $1.8 million R35 Maximizing Investigators’ Research Award (MIRA) from the National Institute of General Medical Sciences (NIGMS). The R35 grant mechanism, which recognizes an individual investigator’s sustained research excellence and potential for groundbreaking research, is one of the most prestigious grants awarded by the National Institutes of Health (NIH).

Newman’s R35 project will explore the impact of redox modification on the function of protein kinases in health and disease. Protein kinases are a family of signaling enzymes that play a central role in regulating essential cellular functions such as metabolism, cell division, cell migration, and programmed cell death. Consequently, the dysregulation of kinase-dependent signaling has been implicated in many pervasive diseases, including diabetes, cancer, cardiovascular disease, and a variety of neurological disorders.

A growing body of evidence suggests that protein kinases are directly regulated by redox modifications. For instance, the reversible oxidation of cysteine residues in redox-sensitive kinases has been shown to influence their activity (both positively and negatively), subcellular localization, and protein-protein interactions. In many cases, the modified cysteine residue is conserved among other members in the same kinase family. This raises the intriguing possibility that reversible oxidation may be a general means of regulating kinase function inside cells.

To explore this hypothesis further, the Newman Lab in the College of Science and Technology is using a combination of complementary biochemical, biophysical, synthetic biology, and computational biology strategies to better understand how redox modification affects interactions between kinases and their cellular ligands. Specifically, the project builds on research conducted as part of an NIGMS-supported SC1 award, where his laboratory demonstrated that oxidation of the canonical CMGC and AGC family members, extracellular signal-regulated kinase 2 (ERK2) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), respectively, alter their global substrate selection by differentially affecting interactions between the kinases and their downstream substrates.

In an article published in iScience, Newman’s team demonstrated that hydrogen peroxide (H₂O₂)-dependent oxidation of ERK2 decreased its affinity for some substrates while increasing its ability to bind others (and having little effect on still others). Similarly, in a paper published in Life, Newman’s group found that while diamide-mediated oxidation of PKA decreases its activity toward a series of model PKA substrates, H₂O₂-dependent oxidation of the kinase by low, physiologically relevant concentrations of H₂O₂ increased its activity toward the same substrates.

The R35 project will expand on these studies by asking questions about 1) the effects of redox modification of kinase substrate selection in various cellular contexts and their impact on signaling outcomes related to disease; 2) the impact of redox modification on the spatiotemporal regulation of kinase activity profiles in cells; and 3) how the global substrate profiles of other protein kinases, including understudied kinases in the “dark kinome,” are affected by H₂O₂-dependent oxidation and/or different types of redox modifications. Together, these studies will offer novel insights into the mechanisms of crosstalk between redox- and phosphorylation-dependent signaling pathways in both physiological and pathological processes.

National Cancer Institute

Through a $2.5 million National Cancer Institute (NCI)-sponsored R01 award, Newman is collaborating with an interdisciplinary team of researchers at the University of North Carolina at Chapel Hill and Tulane University to develop molecular tools, such as genetically targetable kinase activity reporters and small molecule inhibitors, to better understand the regulation of members of the Never-in-mitosis-A-related kinase (NEK) family of kinases. The NEKs are an important, yet understudied, family of mitotic kinases involved in a variety of critical cancer-linked biological processes, including cell cycle regulation, cell motility, RNA splicing, ciliogenesis, the DNA damage response, and inflammation. Consistent with their poorly characterized nature, nine of the 11 NEKs are included in the Illuminating the Druggable Genome (IDG) program, supported by the NIH common fund.

As part of the R01 project, students in Newman’s lab are using functional protein microarrays composed of >21,000 human proteins to identify substrates of each NEK family member and synthetic biology strategies to construct sensitive excitation ratiometric indicator-based NEK activity reporters (ExRai-NEKARs) to track changes in the spatiotemporal regulation of NEK family members in real time in living cells and organoids.

This project is not only offering new insights into the regulation and functional roles of NEK family members in cancer and related disorders, but also providing exciting opportunities for N.C. A&T students to engage in cutting-edge biomedical research that has the potential to positively impact human health.

Department of Defense-sponsored Center of Excellence in Biotechnology

Newman is also working with researchers in the Departments of Chemistry and Chemical, Biological and Bioengineering at N.C. A&T and at the Wake Forest Institute for Regenerative Medicine (WFIRM) to develop new technologies to better understand the impact of various cytotoxic agents on cellular signaling processes in lung, gut, and liver organoids. This project, which is part of the $7.5 million Department of Defense (DOD)-funded Center for Excellence in Biotechnology (CoEB), involves the construction of an integrated microfluidics system that allows changes in signaling dynamics caused by exposure to toxicological and pathological agents to be correlated with changes in the metabolomics profiles of the organoids. This information can be used both to assess the mode of action of existing and emerging threat agents and to inform therapeutic interventions through the principles of systems pharmacology.

The CoEB is also providing integrated research training opportunities for undergraduate students majoring in STEM disciplines such as biology, chemistry, mathematics, and biomedical engineering through the Biotechnology Scholars Program (BSP) at A&T. To date, 12 BSP scholars have conducted research in the Newman laboratory, where the students have contributed to the development of novel genetically encodable fluorescent biosensors and strategies to deliver them to the organoids.

Merck Partnership

Newman is helping to build relationships with industry partners at Merck, one of the premier biopharmaceutical companies in the world. As a member of the Merck-A&T Joint Partnership Team, he helped to establish the Merck Biotechnology Learning Center (MBLC), a 4,025-square-foot facility at the Gateway Research North Campus that includes classroom space, a process laboratory, and state-of-the-art biopharmaceutical manufacturing equipment. Through the MBLC, students and Merck employees are able to gain hands-on training experience and advanced discovery opportunities that enhance academic programming and catalyze biotechnology careers.

Newman has been working together with a team consisting of industry partners at Merck, Rosalind Dale, Ed.D., vice provost for engagement and outreach at A&T, and Nina Davis, director of A&T’s Office of Career Services, to launch a monthly biotechnology seminar series at the university. The seminars provided opportunities for A&T students to interact with professionals at Merck while learning more about various aspects of the biotechnology industry, ranging from drug development to clinical trials to biomanufacturing and working with regulatory agencies. Students engaged in career development activities, learned about internship opportunities at Merck, built their professional networks and visited Merck’s new $1 billion biomanufacturing facility in Durham, North Carolina.

Newman has also helped lead the Merck Biotechnology Summer Camp at A&T. During the one-week camp, 12 high school students from Greensboro and the surrounding area were introduced to core technologies used in the biotechnology industry through hands-on activities. Specifically, students engaged in a guided research project where they learned to express, purify and analyze recombinant proteins, and participated in professional development activities. He and his team will host the camp again this summer, with the goal of introducing students to biomedical research and growing their interest in the biotechnology industry.

Together, these initiatives are offering new insights into the regulation of kinase-dependent signaling processes, building interdisciplinary research teams in academia and industry, and creating exciting opportunities for students to participate in exciting biomedical research initiatives and to learn more about the biotechnology industry.