Derrick Randall

DERRICK RAYMOND RANDALL- MSc DEFENSE

 

“Identification of a Serum Biomarker for Mucopolysaccharidosis I”

 

B. Sc.H., The University of British Columbia, 2003

Tuesday, April 18th, 2006, 12:30 pm, Room K0-155, BC Children’s Hospital

Derrick Randall - MSc defense - pdf

 

SUPERVISORY COMMITTEE

Dr. Lorne A. Clarke, Research Supervisor (Medical Genetics)

Dr. Jan M. Friedman (Medical Genetics)

Dr. W. Robert McMaster (Medical Genetics)

 

 

EXAMINING COMMITTEE

Chair: Dr. Wyeth Wasserman (Medical Genetics)

Supervisory Committee: Dr. Lorne A. Clarke, Research Supervisor (Medical Genetics), Dr. W. Robert McMaster (Medical Genetics)

University Examiner: Dr. Fabio Rossi (Medical Genetics)

 

 

ABSTRACT

The mucopolysaccharidoses are a clinically heterogeneous group of lysosomal storage disorders presenting with broad multi-system disease and a continuous range of phenotypes. Currently there are no objective biomarkers of MPS disease that clearly reflect disease severity or therapeutic responsiveness. Using proteomic studies in the murine MPS I model, I have identified the formation of the heparin cofactor II-thrombin (HCII-T) complex, a well-known serine protease inhibitor (serpin)-serine protease complex, as an informative biomarker for MPS I. MPS I patients showed a range of serum HCII-T concentrations from 16,300–208,600 pM, whereas the control values varied from 34.94 – 1491 pM. HCII-T complex was also elevated in plasma from MPS I patients and mice. The degree of HCII-T complex formation appears to correlate with disease severity and is responsive to therapy. In addition to its role as a biomarker, the discovery of increased serpin-serine protease complex formation provides a valuable insight into possible pathophysiological mechanisms of MPS disease.

 

 

PUBLICATIONS

Derrick R. Randall, Graham B. Sinclair, Karen E. Colobong, and Lorne A. Clarke, “Heparin cofactor II-thrombin complex in MPS I: A biomarker of MPS disease”, Molecular Genetics and Metabolism, In press, Epub 2006 Feb 21.

 

 

PRESENTATIONS

Derrick R. Randall, Graham B. Sinclair, Karen E. Colobong, and Lorne A. Clarke. “Identification of Serum Heparin Cofactor II-Thrombin Complex as a Disease Biomarker in MPS-I.” 9th International Symposium on Mucopolysaccharide and Related Diseases, Venice, Italy, June 29 – July 2, 2006. (Plenary speaker)

 

Derrick R. Randall, Graham B. Sinclair, Karen E. Colobong, and Lorne A. Clarke. “Identification of Serum Heparin Cofactor II-Thrombin Complex as a Disease 13, 2006. (Oral)

 

Derrick R. Randall, Graham B. Sinclair, Karen E. Colobong, and Lorne A. Clarke. “Serum biomarker discovery for MPS disease: Utility of the murine MPS I model.” UBC Medical Genetics 2005 Research Day, Vancouver, BC, November 25, 2005. (Poster)

 

Derrick R. Randall, Graham B. Sinclair, Karen E. Colobong, and Lorne A. Clarke. “Serum biomarker discovery for MPS disease: Utility of the murine MPS I model.” American Society of Human Genetics 2005 meeting, Salt Lake City, UT, October 25 – 29, 2005. (Poster)

 

Derrick R. Randall. “Proteomics in MPS disease study: The value of an animal model.” Centre for Molecular Medicine & Therapeutics TGIF Lecture Series, Vancouver, BC, September 30, 2005. (Oral)

 

Graham Sinclair, Derrick Randall, Karen Yip and Lorne A. Clarke. “Serum prefractionation for isotope-coded affinity tag (ICAT) proteomics and biomarker identification in a murine model of MPS I.” Society for Inherited M Biomarker in MPS-I.” 2005 Garrod Society Symposium, Halifax, NS, May 12 –

 

 

AWARDS

Medical Genetics Graduate Entrance Scholarship

 

 

GRADUATE STUDIES

Field of Study: Mucopolysaccharidoses, lysosomal storage disorders,

and proteomics

 

Courses:

MEDG 419 Human Cytogenetics Drs. C. Brown, L. Lefebvre, and W. Robinson

MEDG 515 Mammalian Developmental Genetics Drs. M. Harris and D. Juriloff

MEDG 520 Advanced Human Molecular Genetics Drs. A. Brooks-Wilson, C. Brown, R. McMaster, F. Rossi, E. Simpson, and W. Wasserman

MEDG 530 Human Genetics Drs. L. Clarke, C. Conibear, M. Harris, B. Leavitt

MEDG 535 Current Topics in Medical Genetics Research Drs. M. Harris and D. Juriloff

Derrick Randall - MSc defense - pdf