Overview

Signaling and Metabolism

Many human diseases, such as diabetes, neurodegeneration, cancer and heart problems, are linked to old age. Our laboratory studies the interface between cellular metabolism and signal transduction, with a specific focus on key steps in glucose and lipid metabolism, in order to understand the ways that nutrients can delay aging effects and thus postpone the onset of disease.

Glucose is a vital, highly regulated metabolite in the human body. Its concentration is tightly controlled within a narrow range by factors secreted from several tissues. Too much glucose uptake leads to systemic problems that partly stem from oxidative stress generated by the mitochondria. Our lab examines the mechanism by which cells control glucose uptake, what regulates the flux from glucose to unwanted lipid accumulation, and how mitochondrial function is affected by glucose concentration.

We utilize a variety of systems and techniques to accomplish our goals. At the atomic scale, we employ cryo-electron microscopy (cryo-EM) to solve the structures of transporter proteins and their regulators. At the cellular level, we investigate how cells respond to metabolic stress. And at the organism level, we integrate cellular responses with systemic responses to understand how diet can modify and curb unwanted oxidative damage. This research will provide better insight into the relationship between diet and health and open the possibility of individualized diet recommendations to delay aging effects.

Our Impact

We’re raising thousands to save millions.

We’re turning hope into action for the millions of people around the world affected by diseases like cancer and Parkinson’s. Find out how you can help us make a difference.

  • 171 studies published from Nov. 1, 2020 to Oct. 1, 2021
  • 68 studies in high-impact journals from Nov. 1, 2020-Oct. 1, 2021
  • 41 clinical trials launched

Ning Wu, Ph.D.

Assistant Professor, Department of Metabolism and Nutritional Programming

Areas of Expertise

Metabolism, diabetes, cell signaling, cancer, protein structure

Biography

Dr. Ning Wu received her Ph.D. in the Department of Biochemistry from the University of Toronto in 2002. She then served as a research associate at The Scripps Research Institute in the Department of Chemistry. In 2004, Dr. Wu joined the Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, as a research fellow where the primary lab focus was to understand the signaling pathways that regulate normal mammalian cell growth and the defects that cause cell transformation. Dr. Wu joined Van Andel Institute in 2013 as an assistant professor.

Project 1

Glucose Metabolism in Cancer

  • Unraveling the molecular mechanisms that regulate glucose uptake in cancers.
  • Investigating the effect of glucose on mitochondria activity.
  • Exploring the role of glucose in the link between metabolic syndrome and cancer incidence.

SELECTED PUBLICATIONS

Dykstra H, Fisk C, LaRose C, Waldhart A, Meng X, Zhao G, Wu N. 2021. Mouse long-chain acyl-CoA synthetase 1 is active as a monomerArch Biochem Biophys 700:108773.

Waldhart AN, Muhire B, Johnson B, Pettinga D, Madaj ZB, Wolfrum E, Dysktra H, Wegert V, Pospisilik JA, Han X, Wu N. 2021. Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissueCell Rep 35(5):109488.

Lee HJ, Jedrychowski MP, Vinayagam A, Wu N, Shyh-Chang N, Hu Y, Min-Wen C, Moore JK, Asara JM, Lyssiotis CA, Perrimon N, Gygi SP, Cantley LC, Kirschner MW. 2017. Proteomic and metabolic characterization of a mammalian cellular transition from quiescence to proliferationCell Rep 20(3):721–736.

Waldhart AN, Dykstra H, Peck AS, Boguslawski EA, Madaj EA, Wen J, Veldkamp K, Hollowell M, Zheng B, Cantley LC, McGraw TE, Wu N. 2017. Phosphorylation of TXNIP by AKT mediates acute influx of glucose in response to insulinCell Rep 19(10):2005–2013.

Wu N, Zheng B, Shaywitz A, Dagon Y, Tower C, Bellinger G, Shen C, Wen J, Asara JM, McGraw TE, Kahn BB, Cantley LC. 2013. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1Mol Cell 49(6):1167–1175.

Christofk HR, Wu N, Cantley LC, Asara JM. 2011. Proteomic screening method for phosphopeptide motif binding proteins using peptide librariesJ Proteome Res 10(9):4158–4164.

Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. 2008. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452:181–186.

Asara JM, Zhang X, Zheng B, Maroney LA, Christofk HR, Wu N, Cantley LC. 2006. In-gel stable isotope labeling for relative quantification using mass spectrometryNat Protoc 1(1):46–51.

Asara JM, Zhang X, Zheng B, Christofk HH, Wu N, Cantley LC. 2006. In-gel stable-isotope labeling (ISIL): a strategy for mass spectrometry-based relative quantificationJ Proteome Res 5(1):155–163.

Summerer D, Chen S, Wu N, Deiters A, Chin JW, Schultz PG. 2006. A genetically encoded fluorescent amino acidProc Natl Acad Sci U.S.A. 103(26):9785-9789.

*Benes CH, *Wu N, Elia AE, Dharia T, Cantley LC, Soltoff SP. 2005. The C2 domain of PKCd is a phosphotyrosine binding domainCell 121(2):271–280.
*Co-authors

Xie J, Wang L, Wu N, Brock A, Spraggon G, Schultz PG. 2004. The site-specific incorporation of p-iodo-L-phenylalanine into proteins for structure determinationNat Biotechnol 22:1297–1301.

Garces RG, Wu N, Gillon W, Pai EF. 2004. Anabaena circadian clock proteins KaiA and KaiB reveal a potential common binding site to their partner KaiCEMBO J 23:1688–1698.

Wu N, Deiters A, Cropp TA, King D, Schultz PG. 2004. A genetically encoded photocaged amino acidJ Am Chem Soc 126(44):14306–14307.

*Anderson JC, *Wu N, Santoro SW, Lakshman V, King DS, Schultz PG. 2004. An expanded genetic code with a functional quadruplet codonProc Natl Acad Sci U. S. A. 101(20):7566–7571.
*Co-authors

Wu N, Pai EF. 2004. Crystallographic studies of native and mutant orotidine 5’-phosphate decarboxylaseTopics Curr Chem 238:23–42.

Wu N, Pai EF. 2002. Crystal structures of inhibitor complexes reveal alternate binding mode in orotidine 5’-monophosphate decarboxylaseJ Biol Chem 277(31):28080–28087.

Wu N, Gillon W, Pai EF. 2002. Mapping the active site-ligand interactions of Orotidine 5’-monophosphate decarboxylase by crystallographyBiochemistry 41(12):4002–4011.

Wu N, Mo Y, Gao J, Pai EF. 2000. Electrostatic stress in catalysis: structure and mechanism of the most proficient enzyme orotidine monophosphate decarboxylaseProc Natl Acad Sci U.S.A. 97(5) 2017–2022.

Wu N, Christendat D, Dharamsi A, Pai EF. 2000. Purification, crystallization and preliminary X-ray study of orotidine 5’-monophosphate decarboxylase. Acta Crystallographica D56(7):912–914.

Christendat D, Yee A, Dharamsi A, Kluger Y, Savchenko A, Cort JR, Booth V, Mackereth CD, Saridakis V, Ekiel I, Kozlov G, Maxwell KL, Wu N, McIntosh LP, Gehring K, Kennedy MA, Davidson AR, Pai EF, Gerstein M, Edwards AM, Arrowsmith CH. 2000. Structural proteomics of an archaeonNat Struct Biol 7:903–909

Holly Dykstra, MPH

Research Associate

Chelsea Fisk

Reseach Technician

Althea Waldhart, B.S.

Senior Research Technician

Jeanie Wedberg

Senior Administrative Assistant II