Assistant Professor

José-Mario Capo-Chichi

Department of Laboratory Medicine & Pathobiology


Toronto General Hospital: University Health Network (UHN)
200 Elizabeth St., Toronto, Ontario Canada M5G 2C4
Clinical Interests
Molecular Genetics
Appointment Status

Dr Capo-Chichi obtained a Doctorate degree in Biochemistry with a concentration in Human Genomics at l’Université de Montréal. His PhD thesis focused on the use of using Next-Generation Sequencing technologies to unravel the genetic bases of non-syndromic forms of Intellectual disability.

Dr Capo-Chichi completed his Clinical Molecular Genetics fellowship at le CHU Sainte-Justine de Montréal. Dr Capo-Chichi received a certification in Personnalized Genomics from the Genome Diagnostics Nijmegen / Radboud University Medical Center in Netherlands.

Dr Capo-Chichi joined the University Health Network in September of 2016 as a clinical molecular geneticist in the Genome Diagnostics division. Dr Capo-Chichi’s interest includes improvement of traditional molecular genetics approaches and development of novel diagnostic tests, particularly in cancer genetics , using high-throughput technologies like Next-Generation Sequencing.


Research Synopsis


My research interest includes improvement of traditional molecular genetics approaches and development of novel diagnostic tests, particularly in cancer genetics, using high-throughput technologies like Next-Generation Sequencing. These translational research activities will focus on the following aspects of molecular pathology:

  1. Genomic alterations in oncology
  2. High-throughput genotyping in cancer
  3. Methylome analysis.

Novel high-throughput genomic technologies are revolutionizing current practice in molecular pathology in many ways, such as facilitating faster diagnosis, tailoring patient management and standard of care, while limiting the need for complementary invasive and expensive investigations. The clinical impact of these methodologies is undeniable; however, key practical questions remain that must be addressed to maximize the usefulness of these techniques in a clinical setting.

Due to the high complexity nature of these new approaches and data interpretations, there is a need for translational research with development and assessment of molecular diagnostic testing in solid and liquid malignancies, and understanding the clinical utility and impact of these tests. This is particularly important as there is increasing use of Next-Generation Sequencing based technologies in clinical diagnostics, leading to many new possible molecular diagnostic tests but with a need for evidence of their clinical utility.

My research interests conducted at the Genome Diagnostics division of the Toronto General Hospital and the Advanced Molecular Diagnostics Laboratory at the Princess Margaret Cancer Center will be centered on:

  1. Genomic alterations in oncology. The molecular bases of cancers are complex and involve genetic lesions at the DNA and RNA level. Next-Generation Sequencing technologies allow combined analysis of DNA-RNA transcripts for detection of pathogenic mutations in solid and liquid malignancies. My research interests in this area will include (a) assessing the diagnostic utility and (b) performance of these testing panels for comprehensive testing.
  2. High-throughput genotyping in cancer. Droplet digital PCR and molecular barcoding are promising methodologies in molecular diagnosis. My research interests will be focus on the usefulness of these high-throughput genotyping tools in molecular pathology for (a) traceability and deep screening of single DNA molecule events, (b) accurate detection of point mutations and copy number variations from limited or compromised DNA specimens like FFPE samples and (c) design of personalized molecular tests for patient screening and disease monitoring.
  3. Methylome analysis. Epigenetic modifications are key factors in the pathophysiology of malignancies; gene silencing through methylation are commonly encountered in cancer. Good examples are glioblastomas characterized by a loss of expression of the MGMT gene due to hyper-methylation in the MGMT promoter region. My research interests in will focus on high-resolution detection of changes in methylation patterns in solid tumors, specifically brain cancer, by targeting critical epigenetic sites for regulation of gene expression including (a) differentially methylated regions (DMRs) in tumor versus normal tissues, (b) gene and miRNA promoters, (c) CpG islands, shores and shelves.


Recent Publications


Srour M, Schwartzentruber J, Hamdan FF, Ospina LH, Patry L, Labuda D, Massicotte C, Dobrzeniecka Capo-Chichi JM et al, Neuroblastoma Amplified Sequence (NBAS) mutation in recurrent acute liver failure: Confirmatory report in a sibship with very early onset, osteoporosis and developmental delay. Eur J Med Genet. 2015. PMID: 26578240.

Capo-Chichi JM, Boissel S et al, Disruption of CLPB is associated with congenital microcephaly, severe encephalopathy and 3- methylglutaconic aciduria. J Med Genet. 2015. PMID: 25650066.

Brue T, Quentien MH, Khetchoumian K, Bensa M, Capo-Chichi JM et al, Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies. BMC Med Genet. 2014. PMID: 25524009.

Hamdan FF, Srour M, Capo-Chichi JM et al, De novo mutations in moderate or severe intellectual disability. PLoS Genet. 2014. PMID: 25356899.

Perrault I, Hamdan FF, Rio M, Capo-Chichi JM et al, Mutations in DOCK7 in individuals with epileptic encephalopathy and cortical blindness. Am J Hum Genet. 2014. PMID: 24814191.

Mehawej C, Delahodde A, Legeai-Mallet L, Delague V, Kaci N, Desvignes JP, Kibar Z, Capo-Chichi JM, et al, The impairment of MAGMAS function in human is responsible for a severe skeletal dysplasia. PLoS Genet. 2014. PMID: 24786642.

Capo-Chichi JM, Ruzzo EK, Ben-Zeev B et al, Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy. Neuron. 2013. PMID: 24139043

Srour M, Chitayat D, Caron V, Chassaing N, Bitoun P, Patry L, Cordier MP, Capo-Chichi JM et al, Recessive and dominant mutations in retinoic acid receptor beta in cases with microphthalmia and diaphragmatic hernia. Am J Hum Genet. 2013. PMID: 24075189.

Capo-Chichi JM et al, Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly. J Med Genet. 2013. PMID: 23687350.

Capo-Chichi JM et al, Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome. Hum Mutat. 2013. PMID: 23033317.

S, Capo-Chichi JM et al, Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population. Am J Hum Genet. 2012.PMID: 22425360.