Medical Genomics Clinical Research Spotlight: Dr. José-Mario Capo-Chichi

Dr. José-Mario Capo-Chichi joined the University Health Network in September of 2016 and has been practicing as a clinical genetics scientist out of Toronto General Hospital (TGH) ever since. He specializes in molecular genetics, with a particular interest in the use of novel high-throughput technologies to improve tumour profiling and enable high-accuracy detection of diagnostic, prognostic, and therapeutic biomarkers in cancer. He is also a guest contributor to two courses in the MHSc Medical Genomics program, speaking to the MedGen students in Advanced Human Genetics (MMG3001Y) and Communicating Genetic Information (MMG3004Y).

Dr. Capo-Chichi holds a Bachelor of Science (BSc) and a Doctor of Philosophy (Ph.D.) degree in biochemistry from Université de Montréal. His post-graduate studies led to the identification of previously uncharacterized genetic causes of neurodevelopmental disorders using whole-exome sequencing and animal models such as mice and zebrafish. His passion for molecular genetics led Dr. Capo-Chichi to transition from academic research to clinical genetics by completing a post-doctoral fellowship in human genetics. Dr. Capo-Chichi is board certified in molecular genetics by the Canadian College of Medical Geneticists (CCMG) and the American Board of Medical Genetics and Genomics (ABMGG).

Dr. Capo-Chichi described his clinical practice at the genome diagnostic laboratory of the Toronto General Hospital as challenging yet rewarding and emphasized, “It’s very rewarding, and I see the direct implication of what I’m doing when it comes to patient management.” In this role, Dr. Capo-Chichi works closely with other clinical colleagues including pathologists, oncologists and genetic counselors to provide the best standard of care to Ontario cancer patients. He highlighted “the importance of ongoing communication and feedback between clinicians and researchers to ensure that the information provided is accurate and up to date.” As he explained, "there's a lot of back and forth. I would say that there's not a day that goes without me getting a call from a clinical colleague and vice versa, explaining a genetic finding and making sure that they're getting the information right". Dr. Capo-Chichi continued, “You are often called to disclose very urgent results that have a [direct] impact on patient management [and] you also need to be able to communicate that information properly. There are many different clinical parameters to integrate. You can't really achieve any of that without the help of your clinical colleagues; it is a transdisciplinary approach.”

Dr. Capo-Chichi felt fortunate to have started his research alongside the advent of next-generation sequencing (NGS) technologies. He described NGS as a “paradigm shift” in molecular genetics and relies on it heavily to screen for mutations in cancer patients: “NGS is a common umbrella term used to describe high-throughput technologies that allow you to screen for DNA and RNA genetic mutations at the scale of the genome.” NGS has revolutionized the way genetic testing is performed in the field of clinical genetics. The technology enables genome-wide analysis, allowing genetics lab scientists professionals to rapidly identify genetic variants associated with various health conditions.

Using NGS, molecular profiling has become a central piece of cancer patients' diagnosis and clinical management. As such, the demand for these high-complexity genetic tests continues to surge, which creates a significant burden for clinical genetics staffs considering the large sample volume, the wide range of genomic targets to interrogate and the constant flow of newly available information on these biomarkers to integrate on clinical reports. The ability to manage this increasing genetic test volume, while maintaining the highest standards of accuracy and quality for patients is paramount to Dr. Capo-Chichi. As he highlighted, one of the biggest challenges with NGS is the high volume of data it generates: “I think the challenge with NGS now is making sense out of the information that you are getting.”

Molecular genetics is a rapidly evolving field, driven by several novel high-throughput methodologies being implemented for clinical use. Consensus guidelines are needed to determine the best approaches to integrate these new tools in the clinical algorithm of cancer patients. Dr. Capo-Chichi is an active member of provincial, national and international consortiums dedicated to optimizing and standardizing the use of these technologies in clinical practice. He is interested in improving classical molecular genetics approaches by establishing the use of novel versatile and highly sensitive molecular assays. For instance, since joining the University Health Network, he has led the development of genetic tests that are currently applied for standard-of-care testing of Ontario patients with acquired hematologic malignancies and central nervous system tumours. Together with other clinical colleagues, Dr. Capo-Chichi is working towards supporting the diagnostic workup of Ontario patients with hereditary hematologic malignancy syndromes.

Dr. Capo-Chichi is also invested in understanding the underlying bases of various forms of hematologic malignancies. His recent work on patients with an inherited form of acute myeloid leukemia is a prime example of collaborative and translational research. In this study, Dr Capo-Chichi and collaborators demonstrated the existence of a genotype-phenotype correlation in individuals with a unique leukemia entity harbouring two disruptive alleles in the DDX41 gene. They further determined the functional impact of previously uncharacterized DDX41 variants identified in these patients, which is critical for proper genetic counseling of such patients with a genetic predisposition to leukemia as well as their family members. Dr. Capo-Chichi spoke on the premise of his upcoming research article, which has been accepted for publication: “We're trying to understand, using different cellular models, the impact of specific mutations that those patients carry on the disease. I feel very grateful to have been part of such a study.”

With his passion and commitment to advancing the field of molecular genetics, Dr. José-Mario Capo-Chichi is on the path to a promising career as a clinical scientist and researcher. We are grateful to Dr. Capo-Chichi for his contributions to the care of cancer patients. We wish him success with his clinical practice and research moving forward.