Dr. Francis Choy

Dr. Francis Choy
Office: CUN 062

Areas of research focus

  • Human molecular genetics
  • Molecular genetics and enzymology of lysosomal storage diseases (LSD), specifically Gaucher disease and Sanfilippo B syndrome
  • Recombinant N-acetyl glucosaminidase expression for potential treatment of Sanfilippo B syndrome
  • CRISPR-Cas9 genome editing and base editors for potential treatment of lysosomal storage disease
  • Stem cell biology in regenerative medicine

My research focuses on lysosomal diseases. I have chosen two autosomal recessive disorders: Gaucher disease and Mucopolysaccharidosis IIIB (MPS IIIB), as models for my study. GD and MPS IIIB result from mutations in the GBA1 and NAGLU gene and lead to deficient glucocerebrosidase and N-acetyl- glucosaminidase activities, respectively. MPS IIIB and Gaucher Types 2 and 3 are characterized by progressive neurodegeneration. Currently, there is no effective treatment since the blood-brain barrier restricts delivery of the therapeutic enzyme to the brain.

We are investigating two approaches to overcome this barrier. One approach utilizes PTD4– a synthetic protein transduction domain modified from the HIV-TAT protein– to facilitate recombinant Naglu-PTD4 delivery across the blood-brain barrier in MPSIIIB.

We also utilize a modified CRISPR/Cas9 gene editing system, called adenine- and cytosine-base editing, to target and correct GBA1 and NAGLU mutations in patient-derived induced pluripotent stem cells, for potential cell therapy in GD and MPS IIIB.

Centre for Biomedical Research - Francis Choy

  • Biol. 230 Genetics (team teach with Dr. Barbara Ehlting) Biol. 436 Human Molecular Genetics
  • Biol. 401A Biotechnology (with Dr. Barbara Ehlting)
  • Biol. 490F Directed Research in Cell and Molecular Biology Biol 499 Honours Thesis Research
  • Biol. 536 Advanced Human Molecular Genetics

Jantzen, R.R., Truelson, S.N., and Choy, F.Y.M. 2013. Human α-N-acetylglucosaminidase: cDNA cryptic site removal and native secretion signal addition significantly enhance enzyme expression and secretion. Process Biochemistry 48:1197-1202. http://dx.doi.org/10.1016/j.procbio.2013.05.007, http://www.sciencedirect.com/science/article/pii/S1359511313002055

Treulson, S.N., Choy, F.Y.M. 2013. Sanfilippo Syndrome: Cellulose affinity purification α-N- acetylglucosaminidase for potential enzyme replacement therapy. Journal of Biochemical and Microbial Technology 1(2):16-19. http://nobleresearch.org/downloadfile.aspx?file=articles\JBMT13-10006.pdf

Jack, A., Amato, D., Morris, G., and Choy, F.Y.M. 2014. Two novel mutations in glucocerebrosidase, C23W and IVS7-1 G>A, identified in Type 1 Gaucher patients heterozygous for N370S. Gene 538:84-87. http://www.sciencedirect.com/science/article/pii/S0378111914000365

Turner, K., and Choy, F.Y.M. 2014. Current methods for the prevention of transmission of mitochondrial DNA diseases. Journal of Molecular and Genetics Medicine 8:127-131, 2014. http://dx.doi.org/http://dx.doi.org/10.4172/1747-0862.1000127

Turner, K., and Choy, F.Y.M. 2015. Treatment of nonsense mutations using stop codon read-through therapeutics and creation of animal models using CRISPR-Cas9. Journal of Molecular and Genetics Medicine 9(3):174-179. http://dx.doi.org/10.4172/1747-0862.1000175

Hoisema, K., Amato, D., Khan, A., Sirrs, S., and Choy, F.Y.M. 2016. Identification of novel splice site mutation IVS9+1(G>A) and novel complex allele G355R/R359X in Type 1 Gaucher patients heterozygous for mutation N370S. Meta Gene 7:47-51. http://dx.doi.org/10.1016/j.mgene.2016.03.003

Choy, F.Y.M. and Christensen, C.L. 2016. Progranulin as a novel factor in Gaucher disease. Christensen, C.L. EBioMedicine http://dx.doi.org/10.1016/j.ebiom.2016.10.010.

Christensen, C.L. and Choy, F.Y.M. 2017. A prospective treatment option for lysosomal storage diseases: CRISPR/Cas9 gene editing technology for mutation correction in induced pluripotent stem cells. Diseases 5, 6-21; doi:10.3390/diseases5010006

Christensen, C.L., Ashmead, R., and Choy, F.Y.M. 2017. Identification and characterization of NAGLU mutations in a Sanfilippo B syndrome patient with a novel genotype (p.Y140C/p.R297X). Archives of Clinical and Biomedical Research 1 (4):200-208. DOI: 10.26502/acbr.50170021

Chu S.S., Christensen, C., and Choy, F.Y.M. 2018. The impact of GC content on CRISPR/Cas9 gene editing: implications for mucopolysaccharidosis type IIIB. Molecular Genetics and Metabolism 123(2):S32. DOI10.1016/j.ymgme.2017.12.061