Research Overview
We study how metabolism mechanistically controls precancer formation and progression in the pancreas and stomach. We are specifically interested in how metabolism guides cell competition dynamics, environmental changes, and cell type-specific behaviors. Our work integrates tools from cell biology, biochemistry, transcriptomics, and metabolomics, using various systems, including clinical samples, animal models, and primary cell cultures. Our current interests are briefly described below.
Tumorigenesis is dependent on changes within the local tissue environment. Additionally, systemic metabolic conditions, including insulin resistance, obesity, and dyslipidemia, are often cancer risk factors. This project aims to investigate how metabolism can change the persistence or restriction of mutant cells within a tissue, define the metabolic mechanisms that healthy cells use to restrain cancer formation, and determine how these metabolic pathways can be leveraged for cancer prevention though dietary intervention.
How do metabolic changes in the environment influence precancer?
We previously discovered that NADPH-producing enzymes restrict precancer formation in the pancreas. Our lab continues to investigate the metabolic landscape of precancer, especially how it differs from established cancer. This project aims to understand how metabolism is altered in cells that border precancerous lesions, determine the metabolic pathways involved in precancer progression, and identify strategies to therapeutically target metabolic vulnerabilities to improve treatment outcomes.
What is the metabolic landscape of precancer?
Selected Publications
A complete list of publications from Dr. Megan Radyk is available on PubMed.
NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions
Radyk MD, Nelson BS, Ruckert MT, Halbrook CJ, Shan M, Alektiar JM, Lavoie BL, Salvatore L, Yan W, Perricone MD, Buscher K, Wood A, Hong HS, Sajjakulnukit P, Zhang L, Corfas G, Bednar F, Frankel TL, Pasca di Magliano M, Colacino JA, Shah YM‡, Crawford HC‡, Lyssiotis CA‡
Accepted in Nature Metabolism. Preprint on bioRxiv. PMC10659312.
The Hallmarks of Precancer
Stangis MM*, Chen Z*, Min J*, Glass SE*, Jackson JO*, Radyk MD*, Hoi XP, Brennen WN, Yu M, Dinh HQ, Coffey RJ, Shrubsole MJ, Chan KS, Grady WM, Yegnasubramanian S, Lyssiotis CA, Maitra A, Halberg RB, Dey N‡, Lau KS‡
Cancer Discovery 2024 Apr 4;14(4):683-689. doi: 10.1158/2159-8290.CD-23-1550. PMC11170686.
Metabolic landscape of the healthy pancreas and the pancreatic tumor microenvironment
Bonilla ME, Radyk MD, Perricone MD, Elhossiny AM, Harold AC, Medina-Cabrera PI, Kadiyala P, Shi J, Frankel TL, Carpenter ES, Green MD, Mitrea C‡, Lyssiotis CA‡, Pasca di Magliano M‡
JCI Insight. 2024 Aug 13;9(18):e180114. doi: 10.1172/jci.insight.180114. PMC11457849.