Faculty Profiles

Dean R. Tolan

Dean R. Tolan

Professor of Biology

PhD, University of California, 1981
Areas of interest: biochemistry, enzymology, molecular and human genetics of enzymes in sugar metabolism
tolan@bu.edu
(617) 353-5310
http://www.bu.edu/aldolase

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.

Courses Taught

  • BI108 Introductory Biology II
  • BI 421 Biochemistry I
  • BI 527 Biochemistry Laboratory
  • MB 722 Advanced Biochemistry

Selected Publications

  • Ritterson Lew C, Tolan DR (2013) "Aldolase Sequesters WASP and Affects WASP/Arp2/3-Stimulated Actin Dynamics" Journal of Cellular Biochemistry, 114, 1928-1939.
  • Ritterson Lew C, Tolan DR (2012) Targeting of several glycolytic enzymes using RNA interference reveals aldolase affects cancer-cell proliferation through a non-glycolytic mechanism. Journal of Biological Chemistry, 287, 42554-42563.
  • Stopa JS, Tolan DR (2011) Stabilization of the predominant hereditary fructose intolerance causing aldolase variant (A149P) with zwitterionic osmolytes. Biochemistry, 50, 663-671.
  • Coffee EM, Tolan DR (2010) Mutations in the promoter region of the Aldolase B gene that cause Hereditary Fructose Intolerance are common among Hispanics and African-Americans. Journal of Inherited Metabolic Disease 33, 715-725.
  • Funari VA, Voevodski K, Leyfer D, Yerkes L, Cramer D, and Tolan DR (2010) Quantitative gene-expression profiles in real time from expressed sequence tag databases. Gene Expression, 14, 321-336.
  • Coffee EM, Yerkes L, Ewen EP, Zee T, and Tolan DR (2010). Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. Journal of Inherited Metabolic Disease 33, 33-42.
  • Malay AD, Allen KN, Tolan DR (2005) Structure of the thermolabile mutant Aldolase B, A149P: Molecular basis of hereditary fructose intolerance. Journal of Molecular Biology 347, 135-144.
  • Funari VA, Herrera VLM, Freeman D, Tolan DR (2005) Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum. Molecular Brain Research 142, 115-122.