Title: Senior Scientist, Genetics & Genome Biology
Alternate Contact Name: Sharu Raveendran
Alternate Phone: 416-813-7654 ext. 309429
Alternate Email: firstname.lastname@example.org
U of T Positions: Professor, Department of Molecular Genetics
Chair Positions: Canada Research Chair in Disease-associated Genome Instability
The Pearson lab research program builds upon the theme initiated over two decades ago to understand the disease-causing mutations of trinucleotide repeat expansions, that lead to diseases like Huntington’s disease and myotonic dystrophy. In the past 15 years, the lab has focused more upon disease-relevant animal models (transgenic mice), DNA repair/replication systems using human cells, human cell extracts or human recombinant proteins. We have also been increasing the relevance and significance of our understanding by assessing instability in true human embryonic stem cells, human fetuses (terminations) and human autopsies, with a focus upon both tissue-specificity and developmental staging of the mutation. In the last two years we have been developing a program of translational research; attempting to harness what we have learned to identify drugs that may be of benefit for affected families. This is crucial toward attaining the lab’s long-term goal of being able to arrest or reverse repeat expansions with the ultimate aim of clinical benefit for the affected individual.
Education and experience
- 2016–Present: Full Professor, Molecular Genetics, University of Toronto, Toronto, ON
- 2004–Present: Senior Scientist, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON
- 1999–2004: Assistant Professor, Molecular Genetics, University of Toronto, Toronto, ON
- 1998–2004: Scientist, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON
- 1994–1997: Lecturer, Institute of Bioscience and Technology, Texas A&M, Texas
- 1994–1998: Postdoctoral Fellow, Texas Medical Center
- 1992–1994: Lecturer, Biochemistry, McGill University, Montreal, QB
- 1989–1994: Ph.D., Department of Medicine, McGill Cancer Center, McGill University, Montréal, QB
- 1986–1989: Bachelor of Science, Cellular & Molecular Biology, Concordia University, Montreal, ON
- 2019: Canada Research Chair, "Chair of Repeat Instability Diseases"
- 2006–2007: International Opportunities Program Award, Canadian Institutes of Health
- 2001–2004: Fragile X Research Foundation of Canada Partnership, Canadian Institutes of Health Research
- 2001–2003: Dean's Fund Award for New Staff Grant, University of Toronto
- 2001: Premier’s Research Excellence Award, Government of Ontario
- 2001–2005: Scholar of the Canadian Genetic Disease Network, Canadian Network Centres of Excellence
- 1999–2004: Scholarship Award, Medical Research Council of Canada
- 1999: Connaught New Staff Matching Grant, University of Toronto
- 1999: Medical Research Council of Can/CIHR Scholarship
- 1999: Human Frontiers Scientific Program Fellowship
- 1997: Member of International Myotonic Dystrophy Consortium, since inception
- 1993: Defi Corporatif Canderel Scientific Exchange Award, Max Plank Institut fur Biochemie
- 1993: Defi Corporatif Canderel Travel Award, Cold Springs Harbor, New York
- 1992–1994: Faculty of Medicine Internal Graduate Studentship, McGill University, Quebec
- 1988: Present member, American Society of Human Genetics
- 2011: Associate Editor, Human Genetics
- 2009: Associate Editor, Journal of Medical Genetics
- 2008: Associate Editor, PLoS Genetics
- Mätlik K, Baffuto M, Kus L, Deshmukh AL, Davis DA, Paul MR, Carroll TS, Caron MC, Masson JY, Pearson CE, Heintz N. Cell Type Specific CAG Repeat Expansions and Toxicity of Mutant Huntingtin in Human Striatum and Cerebellum. bioRxiv [Preprint]. 2023 Jun 8:2023.04.24.538082. doi: 10.1101/2023.04.24.538082. PMID: 37333326; PMCID: PMC10274669.
- Gall-Duncan T, Sato N, Yuen RKC, Pearson CE, 2022, Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences. GenomeRes, 32:1-27.
- Deshmukh AL, Caron MC, Mohiuddin M, Lanni S, Panigrahi GB, Khan M, Engchuan W, Shum N, Faruqui A, Wang P, Yuen RKC, Nakamori M, Nakatani K, Masson JY, Pearson CE, 2021, FAN1 exo- not endo-nuclease pausing on disease-associated slipped-DNA repeats: A mechanism of repeat instability. Cell Reports, 37:110078.
- *Porro A, *Mohiuddin M, Zurfluh C, Spegg V, Dai J, Iehl F, Ropars V, Collotta G, Fishwick KM, Mozaffari NL, Guérois R, Jiricny J, Altmeyer M, Charbonnier JB, *Pearson CE, *Sartori AA, 2021, FAN1-MLH1 interaction affects repair of DNA interstrand cross-links and slipped-CAG/CTG repeats. Science Advances, 7:eabf7906. *co-Sr. authors. N&V in Cell Reports, 7:eabf7906, *co-first and co-senior authors.
- Nakamori M, Panigrahi GB, Lanni S, Gall-Duncan T, Hayakawa H, Tanaka H, Luo J, Otabe T, Li J, Sakata A, Caron MC, Joshi N, Prasolava T, Chiang K, Masson JY, Wold MS, Wang X, Lee MYWT, Huddleston J, Munson KM, Davidson S, Layeghifard M, Edward LM, Gallon R, Santibanez-Koref M, Murata A, Takahashi MP, Eichler EE, Shlien A, Nakatani K, Mochizuki H, Pearson CE. (2020) A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo. Nature Genetics. 52(2), doi: 10.1038/s41588-019-0575-8, PMID:32060489.
(Cover illustration, cover feature, and News & Views: Nature Genetics, 2020, 52:136-137).
- 2021–2023: Modulating the ALS-associated C9orf72 Repeat Expansion and Expression, Principal Investigator, Brain Canada, Operating Grant
- 2020–2025: DNA repair proteins as modifiers of CAG repeat instability in Huntington's disease, Principal Investigator, Canadian Institute of Health Research
- 2019–2020: Automated Epifluorescent Metaphase & Tissue Microscope, Principal Investigator, Canadian Foundation for Innovation, Equipment
- 2019–2022: Somatic DNA mosaicism of the ADNP gene in cells, ADNP-mouse tissues and issues of a post-mortem ADNP individual: An indication of how this may affect disease, Principal Investigator, Canadian Institute of Health Research, Operating Grant
- 2016–2021: Nucleic acid-binding ligands as modulators of repeat instability for therapeutic benefit against neurological and neuromuscular diseases, Principal Investigator, Canadian Institute of Health Research, Project Scheme Operating Grant
- 2015–2022: Formation and biological functions of unusual DNA/RNA structures formed by repeat Sequences, Principal Investigator, Natural Sciences and Engineering Research Council, Discovery Grant
- 2017–2019: The Genetic Factors of CTG/CAG Repeat Contraction in Repeat Instability Families, Principal Investigator, The University of Toronto McLaughlin Centre
- 2016–2017: Unusual nucleic acid structures in C9orf72-related ALS/FTD repeat instability, Principal Investigator, ALS Society of Canada, Bridging Grant
- 2016–2018: Modulating HD CAG repeat instability for clinical benefit, Principal Investigator, Huntington Society of Canada, NAVIGATOR
- 2016–2017: Myotonic dystrophy and congenital form: genetic and epigenetic marks associated with CTG/CAG repeat instability, Principal Investigator, Canadian Institute of Health Research, Bridge Fund
- 2016–2019: Gozes (Co-PI), Kooy (Co-PI); Team Grant: European Research Projects on Neurodevelopmental Disorders. Modelling syndromic autism caused by mutations in the ADNP gene, Principal Investigator, Canadian Institute of Health Research - Institute of Neurosciences, Mental Health and Addiction (CIHR-INHMA)
- 2015–2016: Unusual nucleic acid structures in C9orf72-related ALS/FTD repeat instability, Principal Investigator, ALS Society of Canada, Bridging Grant
- 2015–2018: Nucleic acid-binding ligands as modulators of repeat instability for therapeutic benefit, Principal Investigator, Canadian Institute of Health Research, Bridge Fund
- 2015–2018: Stabilization of ALS/FTD hexanucleotide repeats via modulation of a repair protein interaction to reverse disease progression, Principal Investigator, Weston Brain Institute