Research Interests

• Lysosomal storage diseases
• Enzyme structure and function
• Gene therapy
• Lysosomes and prostheses
• Animal models

Research Activities

Beta-Galactosidase (Gal) activity is deficient in two distinct diseases (GM1-gangliosidosis and Morquio disease, type B) involving mutations in the same gene. We have identified two active site residues and are determining their catalytic roles. A second research focus concerns how the mutations cause these diseases. Knowledge of the molecular aspects of Gal is essential to understand how Gal functions and the pathophysiology of these diseases.

Failure of hip arthroplasties is a significant burden to the health care system. A collaborative project focuses on the role of phagolysosomes in the macrophage digestion of polyethylene particulates. In a collaborative project, we are developing liposome-DNA approaches to treat adult Gaucher's disease.

External Funding

Fondation Leducq: Translatantic network to define mechangisms, mediators and clinical applications of remote ischemic preconditioning

Publications

Zhang H, Mahuran DJ, Callahan JW. Identification of proteins in the ceroid-like autofluorescent aggregates from liver lysosomes of Beige, a mouse model for human Chediak-Higashi syndrome. (2010). Mol Genet Metab. 99: 389-395.

Shimizu M, Tropak M, Diaz RJ, Suto F, Surendra H, Kuzmin E, Li J, Gross G, Wilson GJ, Callahan JW, Redington AN. Transient limb ischemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence for cross-species protection. (2009). Clinical Sci 117: 191-200.

Callahan JW, Bagshaw RD, Mahuran DJ. The integral membrane of Lysosomes: its proteins and their roles in disease. (2009) J Proteomics 72: 23-33

Bukovac SW, Bagshaw RD, Rigat BA, Callahan JW, Clarke JTR, Mahuran DJ. Cryptic splice site in the complementary DNA of glucocerebrosidase causes inefficient expression. (2008). Analyt Biochem 381:276-278.

Martin DR, Rigat BA, Foureman P, Varadarajan GS, Hwang M, Krum BK, Smith BF, Callahan JW,  Mahuran DJ, Baker HJ. Molecular consequences of the pathogenic mutation in feline GM1 gangliosidosis. (2008). Mol Genet Metab. 94:212-221.

Wang L, Oka N, Tropak M, Callahan JW, Lee J, Wilson G, Redington A, Caldarone CA. Remote ischemic preconditioning induction of a transferable blood-borne effector that protects mitochondrial structure and function and preserves myocardial performance after neonatal cardioplegic arrest. (2008). J Thor Cardiovascular Surg. 136:335-342.

McCready ME, Carson NL, Chakraborty P, Clarke JTR, Callahan JW, Skomorowski MA, Chan A, Bamforth F, Casey R, Rupar CA, Geraghty MT. Development of a clinical assay for detection of GAA mutations and characterization of the GAA mutation spectrum in a Canadian cohort of individuals with glycogen storage disease, type II. (2007). Molec Genet Metab 92: 325-335. Epub 2007, Aug 27.

Santamaria R, Chabas A, Callahan JW, Grinburg D, Vilageliu L. Expression and characterization of 14 GLB1 mutant alleles found in GM1 gangliosidosis and Morquio B patients. (2007). J Lipid Res 48: 2275-2282. Epub 2007, Jul 30.

Zhang H, Fan X, Bagshaw R, Zhang L, Mahuran DJ, Callahan JW (SRA). Lysosomal membranes from beige mice contain higher than normal levels of endoplasmic teticulum proteins. (2007). J Proteome Res, 6 (1): 240-249, 2007.

Lepage N, Li D, Kavsak PA, Bamforth F, Callahan JW (PA), Dooley K, Potter M. Incomplete pediatric reference intervals for the management of patients with inborn errors of metabolism. (2006) Clin Biochem 39(6): 595-505.