ABOUT US RESEARCHERS - SUZANNE LEWIS

Suzanne Lewis, MD, FRCPC, FCCMG

email: slewis@cw.bc.ca

SUMMARY OF RESEARCH:

A dedication to clinical genetics patient care has nurtured my long-standing interest in somatic and behavioural phenotype analysis and patterning, and their relationship to the genetic basis of developmental disabilities in children and adults. This has led to several collaborative findings describing important phenotype-genotype correlations while also providing new insight into the molecular etiology and syndromic relationships of a variety of inherited developmental handicaps, including: 17q23 micro-deletion syndrome, Fragile X syndrome, epilepsy syndromes, Prader-Willi syndrome, X-linked mental retardation (XLMR) and, in particular, Autism Spectrum Disorder (ASD). Collaborating internationally, we were successful in significantly refining and ultimately identifying the specific disease locus (the human homolgue of the Aristaless ( ARX ) gene) linked with a debilitating type of common childhood myoclonic epilepsy (infantile spasms) underlying a severe syndrome of XLMR (West syndrome), dystonia (Partington syndrome) and other forms of XLMR. This work re-emphasized the value of acquiring and translating new knowledge through liaison between the clinic and laboratory.

The goal of our research program is to continue to develop a strong "bench to bedside" framework for further contributing to genetic knowledge underlying the identification, understanding and treatment of both rare and common childhood and adult developmental disabilities, particularly Autism Spectrum Disorder (ASD). Our greatest accomplishments in this area are the collective inspiration and success achieved working with colleagues here at the Children's & Women's Health Centre of BC and the University of BC, as well as across Canada and the US through the ASD-Canadian American Research Consortium (ASD-CARC; http://www.autismresearch.ca/ ), with which I am a Principal Investigator and co-recipient of a CIHR Interdisciplinary Health Research Team Program Grant (with Dr. Jeanette Holden, Queen's University) to help support our collaborative work in unravelling the complex genetics and phenotypes of ASD.

In the laboratory, past work has focussed in the area of applied gene therapy technologies involving viral and non-viral gene transfer. My experiences in this field have specifically targeted the application of gene transfer and expression technology toward better understanding the biologic and pathologic basis of lipoprotein disorders. Future goals are to coalesce the tools of clinical genetic study with those of somatocellular gene transfer, expression and animal modeling to better understand the molecular pathways and pathologies which predispose to ASD and other common, and rare, childhood and adult disorders of brain neurodevelopment.

Current research projects include:

• Unravelling the mysteries of Autism Spectrum Disorder: from genotyping and phenotyping to prospective identification and management (CIHR-IHRT funded to 2005)

• Application of novel approaches for identifying culprit genes in Autism Spectrum Disorder using genomic microarrays and molecular assessments of duplicon-mediated microduplications and microdeletions (CIHR funded to 2006)

• Development of an interdisciplinary health research network aimed to reduce health disparities in intellectually disabled individuals (the HEIDI Program: Healthcare Equity for Intellectually Disabled Individuals) (CIHR funded to 2004)

• Development of a transdisciplinary inter-institute training program in Autism Spectrum Disorders (CIHR funded Strategic Training Program Recipient to 2009)

• The epidemiology of ASDs in BC/Yukon and the establishment of a national epidemiologic database for the study of autism in Canada (NEDSAC) CIHR-IHRT funded to 2005)

• Early identification of infants at risk for autism (March of Dimes in application)

RELEVANT PUBLICATIONS:

Lewis MES. The complicity of segmental duplicity in human genomic disease (2003). Clin Genetics: 63:262-267.

Lewis MES. Dissecting the genetic bases of brain form, function and phenotype (2002). Clin. Genetics 62(2):104-109.

Strømme P, Mangelsdorf ME, Shaw MA, Lower KM, Lewis MES, Bruyere H, Lütcherath V, Gedeon AK, Wallace RH, Scheffer IE, Turner G, Partington M, Frints S, Fryns J-P, Sutherland GR, Mulley JC and Gécz J. Mutations of the human ortholog of Aristaless cause X-linked mental retardation and epilepsy (2002). Nature Genetics 30(4):441-445.

Lewis, MES. Refining the spectrum of genes in autism spectrum disorder (2002). Clin. Genetics 61(1):7-13.

Lewis, MES. Gene expression and therapy in lipoprotein disease models - Getting to the heart of the matter (2001). Clin. Genet 59(6):587- 592.

Lewis MES. Real facts from artificial chromosomes (2001). Clin. Genetics: 59(1):12-16.

Penaherrera MS, Barrett IJ, Brown CJ, Langlois S, Yong S-L, Lewis MES, Bruyere H, Howard-Peebles P, Kalousek DK and Robinson WP. An association between skewed X-chromosome inactivation in diploid fetal tissues and abnormal outcome in mosaic trisomies predominantly confined to the placenta (2000). Clin. Genetics: 58(6):436-446.

Lewis MES. Altering the Pathway To Human Gene Therapy (2000). Clin. Genetics: 58(1):12-15. Bruyere H, Wood S, MacLeod PJ, Langlois S and Lewis MES (2000). A new X-linked mental retardation/epilepsy gene localized to Xp21.3-Xp22.1 (West Syndrome). Excerpta Medica: Search on Epilepsy: 7(2):21-23.