UNIVERSITY PARK, Pa. — Melanie McReynolds, Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biochemistry and Molecular Biology, has been honored with a Faculty Early Career Development (CAREER) award from the U.S. National Science Foundation (NSF). The CAREER award is NSF’s most prestigious award in support of early-career faculty members who can serve as academic role models in research and education and lead advances in the mission of their department or organization.
The five-year, $1.3 million CAREER award will support McReynolds’ research to understand a molecule called NAD+, which is present in all living organisms and involved in a wide variety of cellular processes. Low levels of NAD+ have been linked to aging and a wide range of diseases, including Type 2 diabetes, Alzheimer’s and cancer.
“NAD+ is at the center of metabolism, cell-to-cell communication, stress responses and more,” McReynolds said. “We know that levels of this critical molecule decrease with cellular stress and with aging, but there are gaps in our understanding of why this happens and how NAD+ is involved in regulating stress. Using a wide variety of techniques, we plan to map out how NAD+ is used across the lifespan and under stressful conditions, which could help us understand the basis of aging and ultimately to age healthier.”
McReynolds and her research group use the nematode worm, Caenorhabditis elegans, as a model system. Nematodes use NAD+ in a similar way to humans and other animals at the cellular level. Because these transparent worms complete their lifecycle in three to four weeks, it is possible to document cellular process throughout their lifespan. The group will use a multi “omics” approach, using techniques from metabolomics, transcriptomics and proteomics to assess how the molecules work in the systems as a whole, as well as directly tracking metabolites — the molecules produced by the metabolism process — via a process called isotope tracing that follows individual atoms through metabolic processes and biosensors, to better understand NAD+ function and regulation under normal conditions, under stressful conditions and during aging in the worms.
“Undergraduates in my lab are also performing manipulations in the worms, for example by supplementing NAD+, to understand its impact on behavior, reproduction and lifespan,” McReynolds said. “NAD+ supplements, including B3 supplements, are a million-dollar industry — projected to become a billion-dollar industry over the next decade, but how exactly they work, and the consequence of overtaking supplements, remains unclear.”
Additionally, McReynolds will establish “Science in Action” workshops for middle and high school students in Winston County, Mississippi. Younger participants will gain exposure to basic science experiments, while older participants will have an opportunity to see how metabolism of C. elegans is impacted by various stressors.
“My students and I will return to my hometown, Louisville, Mississippi, every summer to share our experiences and journeys in science and to lead hands-on experimental activities related to cellular metabolism and aging,” she said. “Eventually, we hope that students who have participated over multiple years will serve as mentors to younger students.”
McReynolds’ awards and honors include being named an inaugural fellow of the multi-institution Intersections Science Fellows Symposium in 2021, a Rising Star in Health Sciences Research in the field of metabolism by the University of Utah in 2021, a Hanna H. Gray Fellow by the Howard Hughes Medical Institute in 2018 and a member of the Burroughs Wellcome Fund Postdoctoral Research Enrichment Program in 2018. As a postdoctoral researcher, she was recognized as a Rising Star on the Cell Press list of Top 100 Inspiring Black Scientists in America. Her research has been published in journals such as Nature, Science, Nature Metabolism and Cell Systems.
Prior to joining the faculty at Penn State, McReynolds was a postdoctoral researcher at Princeton University from 2017 to 2021. She earned a master’s degree in biological sciences from Alcorn State in 2011 while participating in the Alcorn State to Penn State Bridges to the Doctorate Program, and a doctoral degree in biochemistry and molecular biology at Penn State in 2017.