• Title Professor of Biology; Director of Undergraduate Studies
  • Education PhD, University of California
  • Web Address http://www.bu.edu/aldolase/
  • Phone 617-353-5310
  • Area of Interest biochemistry, enzymology, molecular and human genetics of enzymes in sugar metabolism
  • CV

Current Research

Virtually all organisms contain the glycolytic enzyme fructose bisphosphate aldolase. Vertebrates have three distinguishable isoforms of the enzyme; aldolase A, B, and C. Each of these isozymes has different tissue distribution and catalytic properties appropriately for their roles in sugar metabolism. The aldolases have also been implicated in a number of moonlighting functions involved in cell motility, infection, insulin signaling, and endocytosis. It is the goal of the laboratory to understand the biochemical, evolutionary, and developmental mechanisms responsible for the distinguishing features of the various aldolases.

Structure and function of aldolases — The structural and functional details of this ancient and essential glycolytic enzyme are being investigated by structural analysis via x-ray crystallography and electron microscopy of the structures of the different isozymes complexed with substrate or inhibitor.

Characterization of the genetic defects in hereditary fructose intolerance (HFI) — Mutations in the aldolase B gene manifest themselves in HFI, a genetic disorder that can cause liver disease, coma, and death. It is especially problematic for newborn infants at the time they are weaned to fructose-containing foods. A mouse knock-out model is being used to study the disease and mutations from HFI patients of different ethnic groups are being determined.

Evolution of the aldolases — Current projects include the characterization of moonlighting functions that have evolved by oblating these functions with RNAi and mutant forms of the enzyme in tissue culture cells.

Selected Publications

  • Andres-Hernando, A., D.J. Orlicky, M. Kuwabara, C. Cicerchi, M. Pedler, M.J. Petrash, R.J. Johnson, D.R. Tolan, and M.A. Lanaspa (2023). Endogenous Fructose Production and Metabolism Drive Metabolic Dysregulation and Liver Disease in Mice with Hereditary Fructose Intolerance. Nutrients 15:4376.

  • Hicks, K.G., A.A. Cluntun, H.L. Schubert, S.R. Hackett, J.A. Berg, P.G. Leonard, M.A. Ajalla-Aleixo, Y. Zhou, Bott, A.J., S.R. Salvatore, F. Chang, A. Blevins, P. Barta, S. Tilley, A. Leifer, A. Guzman, A. Arok, S. Fogarty, J.M. Winter, H.C. Ahn, K.N. Allen, S. Block, I.A. Cardoso, J. Ding, I. Dreveny, C. Gasper, Q. Ho, A. Matsuura, M.J. Palladino, S. Prajapati, K.K. Sun, K. Tittmann, D. R. Tolan, J. Unterlass, A.P. VanDemark, M.G. Vander Heiden, B.A. Webb, C.H. Yun, P.K. Zhao, B. Wang, F.J. Schopfer, C.P. Hill, M.C. Nonato, F.L. Muller, D.E. Gottschling, J.E. Cox, and J. Rutter (2023). Protein-Metabolite Interactomics of Carbohydrate Metabolism Reveal Regulation of Lactate Dehyrogenase. Science 379:996-1003.

  • Landaverde, L., D. McIntyre, J. Robson, D. Fu, L. Ortiz, R. Chen, S.M.D. Oliveira, A. Fan, A. Barrett, S.P. Burgay, S. Choate, D. Corbett, L. Doucette-Stamm, K. Gonzalez, D.H. Hamer, L. Huang, S. Huval, C. Knight, C. Landa, D. Lindquist, K. Lockard, T.L. Macdowell, E. Mauro, C. McGinty, C. Miller, M. Monahan, R. Moore, J. Platt, L. Rolles, J. Roy, T. Schroeder, D.R. Tolan, A. Zaia, R.A. Brown, G. Waters, D. Densmore, and C.M. Klapperich (2022). Buildout and integration of an automated high-throughput CLIA laboratory for SARS-CoV-2 testing on a large urban campus. Society for Laboratory Automation and Screening Technology 27:302-311.  

  • Hui, M.H., K. Rhine, and D.R. Tolan (2021). Actin filament- and Wiskott-Aldrich syndrome protein-binding sites on fructose-1,6-bisphosphate aldolase are functionally distinct from the active site. Cytoskeleton 78:129-141. 

  • Nakagawa, T., M.A. Lanaspa, I. San Millan, M. Fini, C.J. Rivard, L.G. Sanchez-Lozada, A. Andres Hernando, D.R. Tolan, and R.J. Johnson (2020). Fructose contributes to the Warburg effect for cancer growth. Cancer Metabolism 8:16.

  • Buziau, A.M., C.G. Schalkwijk, C.D.A. Stehouwer, M.C.G.J. Brouwers, and D.R. Tolan (2020). Recent advances in the pathogenesis of hereditary fructose intolerance:   implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease. Cellular and Molecular Life Sciences 77:1709-1719.

  • Johnson, R.J., P. Stenvinkel, P. Andrews, L.G. Sánchez-Lozada, T. Nakagawa, E. Gaucher, A. Andres-Hernando, B. Rodriguez-Iturbe, C.R. Jimenez, G. Garcia, D.H. Kang, D.R. Tolan and M.A. Lanaspa (2020). Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts. Journal of Internal Medicine  287:252-262.

  • Lanaspa, M.A., A. Andres-Hernando, D.J. Orlicky, C. Cicerchi, C. Jang, N. Li, T. Milagres, M. Kuwabara, M. Wempe, J.D. Rabinowitz, R.J. Johnson, and D.R. Tolan (2018). Ketohexokinase C Blockade Ameliorates Fructose-Induced Metabolic Dysfunction in Fructose-Sensitive Mice. Journal of Clinical Investigation 128:2226-2238.

  • Jensen, T., M.F. Abdelmalek, S. Sullivan, K.J. Nadeau, M. Green, C. Roncal, T. Nakagawa, K.J. Masanari, M. Kuwabara, Y. Sato, D.H. Kang, D.R. Tolan, L.G. Sanchez-Lozada, H.R. Rosen, M.A. Lanaspa, A.M. Diehl, and R.J. Johnson (2018). Fructose and Sugar: A Major Mediator of Nonalcoholic Fatty Liver Disease. Journal of Hepatology 68:1063-1075.

Courses Taught:

  • BI108 Introductory Biology II
  • BB 421 Biochemistry I
  • BB 422 Biochemistry II
  • MB 722 Advanced Biochemistry

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