• Genotype/phenotype correlations of novel genomic anomalies underlying susceptibility to the Autism Spectrum Disorders (ASDs)
• Improving the health of children with genetic causes of idiopathic neurodevelopmental disability
• Longitudinal studies of the incidence and prevalence of Autism Spectrum Disorders in BC and Canada
• Development of novel approaches for the early recognition, management and intervention of Autism Spectrum and related developmental disorders
• Genetics and neurobiology of developmental disabilities (West Syndrome, Myoclonic Epilepsy)
• Behavioural phenotype patterning in disorders of neurodevelopment
• Gene therapy

My dedication to clinical genetics patient care has nurtured my long-standing interest in somatic and behavioral phenotype patterning, and their respective relationship to the genetic basis of autism spectrum and related neurodevelopmental conditions. Examples include collaborative work identifying the Aristaless (ARX) gene) as the disease-specific locus contributing to childhood myoclonic epilepsy and X-linked Mental Retardation (XLMR; West Syndrome), now estimated to account for ~10% of all XLMR cases (Nature Genetics, April, 2002).

As Co-Director of the Autism Spectrum Disorders-Canadian American Research Consortium (ASD-CARC) and Leader of the BC Autism Spectrum Interdisciplinary Research (ASPIRE) Program, we have uncovered several new genomic findings and their clinical correlates involving 5p15.2, 15q11-q13 and newly recognized ASD/ID microdeletion syndromes involving 2p15.1-16 and Xp11.2. The description of clinical and biological correlates of ASD, including those harbouring submicroscopic deletions and duplications, has advanced novel endophenotyping approaches such as 3D craniofacial imaging to delineate atypical face-brain asymmetry – now recognized as an etiologically informative endophenotype of ASDs since publication of our team’s seminal work [Molecular Psychiatry 2008 [June]: 13(6):614-623. 

My clinical research interests are founded and strengthened through longstanding multidisciplinary team engagement with colleagues locally, nationally and internationally in the characterization of novel clinical genetic and genomic syndromes contributing to autism spectrum and related neurodevelopmental disorders. This work underscores the significant value of discovering new knowledge learned via the two-way translation of work between the laboratory bench and patient care in the clinic.

The work of the BC ASPIRE Program continues to cultivate this two-way translational framework for further contributing to genetic knowledge underlying the identification, understanding and treatment of childhood and adult neurodevelopmental disabilities, with a focus on autism and related neurodevelopmental disorders.  Current research projects include:

• A comprehensive approach for identifying genes for complex genetic disorders: Autism spectrum disorders and beyond (CFI-LEF funded)
• The identification of susceptibility genes and phenotypic subgroups of autism spectrum disorders (ASDs); (CFRI, MSFHR and CIHR funded) 
• Identifying phenomic co-morbidities of autism spectrum disorders and their genomic etiologies (CIHR, CFRI, MSFHR and Autism Speaks funded)
• Medical, physical and biological endophenotypes of the autism spectrum disorders (CIHR and Autism Speaks funded)
• A transdisciplinary inter-institute training program in Autism Spectrum Disorders (CIHR funded STIHR)
• The epidemiology of ASDs in BC and Canada; A national epidemiologic database for the study of autism in Canada (NEDSAC) (CIHR funded)
• Knowledge to action initiatives - AutismCONNECTS (www.AutismCONNECTS.ca): Developing a virtual community for autism spectrum stakeholders (CIHR funded)
• Improving the health of children with intellectual disabilities by early identification of genetic causes (CIHR funded)

Qiao Y, Riendeau N, Harvard C, Liu X, Hildebrand MJ, Holden JJA, Rajcan-Separovic E and Lewis MES. Phenomic Determinants of Genomic Variation in Autism Spectrum Disorders. [Epub Online First 21 July 22]; J Med Genet; 2009, in press.

Liu X, Novosedlik N, Wang A, Hudson M, Cohen I, Chudley AE, Forster-Gibson CJ, Lewis MES, Holden JJA. The DLX1and DLX2 genes and Susceptibility to Autism Spectrum Disorders. Eur J Hum Genet; 2009 Feb; 17(2):228-35. PMID: 18728693. 

Qiao Y, Liu X, Harvard C, Hildebrand MJ, Rajcan-Separovic E, Holden JJA and Lewis MES. Autism-associated microdeletion of Xp11.22. Clin Genet 2008 [August]: 74(2): 134-144.  PMID: 18498374.

Ouellette-Kuntz H, Coo H, Lloyd JEV, Kasmara L, Holden JJA and Lewis MES. Trends in Autism Prevalence: Diagnostic Substitution Revisited. J Autism Dev Disord 2008 Jul; 38(6):1036-1046. PMID: 17975721.

Hammond P, Forster-Gibson C, Chudley A, Farrell S, MacKenzie J, Allanson JE, Holden JJA, Hutton T and Lewis MES. Face-Brain Asymmetry in Autism Spectrum Disorders. Molec Psychiatry 2008 [June]: 13(6):614-623. PMID: 18317467.

Lopez-Rangel E, Mickelson ECR and Lewis MES. The Value of a Genetic Diagnosis for Individuals with Intellectual Disabilities: Optimizing Healthcare and Function across the Lifespan. Br J Dev Disab 2008 [July]: 54(2) No. 107:69-82.  

Qiao Y, Harvard C, Riendeau N, Fawcett C, Liu X, Holden JJA, Lewis MES, Rajcan-Separovic E. Putatively benign copy number variants in subjects with idiopathic autism spectrum disorder and/or intellectual disability. Cytogen Genome Res [Dec] 2008: 123, 79-87. 

Ouellette-Kuntz H, Coo H, Lloyd JEV, Kasmara L, Holden JJA and Lewis MES. Trends in assignment of special education codes for autism in British Columbia: Implications for autism prevalence estimates. [Epub Jan, 2007]; J. Autism Dev. Dis. 2007: 37, 1041-1948.

Rajcan-Separovic E, Harvard C, McGillivray B, Hall JG, Qiao Y, Hurlburt J, Hildebrand J, Mickelson E, Holden JJA and Lewis MES. Clinical and Molecular Cytogenetic Characterization of a Newly Recognized Microdeletion Syndrome involving 2p15-16.1 [Epub Online First: Sept. 8, (2006)]; J Med Genet 2007: 44, 269–276.

Mercer L, Creighton S, Holden JJA and Lewis MES. Parental perspectives on the causes of Autism Spectrum Disorder in their children. J. Genet. Counseling 2006: 15, 41-50.

Michael Smith Foundation for Health Research Career Investigator Award – Clinician Scholar

CIHR Short Term Clinician Investigator Research Award – 2005

CIHR Institute of Genetics Clinician Investigator Award – 2003-05

Patents:

U.S. Patent #: 5658729 (August 19, 1997) – Method, Reagent and Kit for Evaluating Susceptibility to Premature Atherosclerosis.

U.S. Patent Application # 08/737954 (pending): Recombinant Viruses, Preparation and Use Thereof in LPL Gene Therapy.

EP European Patent Office (EPO) Application Number: EP1995000920972: RECOMBINANT VIRUSES, PREPARATION AND USE THEREOF IN GENE THERAPY: BENOIT, Patrick; DENEFLE, Patrice; PERRICAUDET, Michel; HAYDEN, Michael and LEWIS, Suzanne. Published / Filed: March 19, 1997/ May 22, 1995.

Levina Kasmara – Research coordinator, Autism Spectrum Interdisciplinary Research (ASPIRE) Program

Jeanette Hildebrand, RN – Clinical/Research Genetic Counsellor, Clinic Manager, ASPIRE Program
Simone Dharmaratne, Assistant Clinic Manager, ASPIRE Program
Jane Hurlburt, MSc, RN, – Clinical Genetic Counsellor, Provincial Medical Genetics Program
Prescilla Carrion, H.BSc, MSc – CIHR-STIHR Research Genetic Counsellor
Elena Lopez, MD, FRCPC, FCCMG – Autism Speaks and CIHR-STIHR Postdoctoral Fellow
Ying Qiao, PhD – CIHR-STIHR Research Associate
Noemie Riendeau, H.BSc – Graduate student
Chansonette Harvard, H.BSc, MSc – Research assistant
Kathleen Mayberry, H.BSc – Genetic Counsellor trainee and work study project assistant