Ian Tobias

 itobias@uoguelph.ca
 Office: Biomed 3603
 519-824-4120 Ext. 54948

 Lab: Biomed 3638
 519-824-4120 Ext. 54685

Profile

Core Interests

• Using comparative genomics to study the evolution of gene regulation in neural development.
• Integrating genome editing and stem cells to create models of mammalian development.
• Cis-regulatory elements (e.g., enhancers, insulators, promoters) in cell differentiation and patterning of neural tissues.
• Regulation of chromatin remodeling by transcription factors and epigenetic modifiers in cell fate reprogramming and cancer.
• Improving veterinary advanced cell therapeutics with genetic technologies.

Research Interests

The biological mechanisms that regulate brain development are conserved across mammals and lower vertebrates, yet neurodevelopment displays remarkable variation both across species (e.g., evolution) and within species (e.g., neurological traits and disease susceptibility). Why do animals and humans display variation in neurological traits and disease risk, and what genes and cell types drive such variation?

My lab seeks to map and understand the gene regulatory networks that control the fate of stem cells and their derivatives. Using a breadth of computational and empirical methods, we are taking a multi-species comparative approach to understand how changes in DNA sequence affect gene regulation and contribute to evolution. We also leverage our core expertise in gene regulation to study the underlying mechanisms of inherited neurological disorders with a goal discovering genetic and epigenetic changes with diagnostic value, and developing treatment strategies for what are presently untreatable disorders.

Our lab uses functional genomics and genome-editing techniques to address several curiosity-driven questions that motivate our research: Can we define a set of core regulatory elements that confer a lineage identity and establish cell types? Are some of the regulatory architectures controlling genes inherently more robust than others? Can gene regulation be tuned to mimic how mammalian cell types evolve diverse functions and susceptibility to disease?

My lab also investigates the genetic causes of heritable movement disorders in humans and companion animals. Despite our accumulated knowledge of the human genome, we still do not have genetic tests that can tailor prevention and treatment strategies to the specific patho-mechanistic features of a patient subgroup. We are currently interested in a diverse collection of genetic disorders that result from inborn errors in brain and spinal cord development called spinocerebellar ataxias. We use stem cells to create innovative physical models of neurodevelopment to understand how different neural cell types are formed in the correct place and at the right time; and how these processes go awry in disease.

Selected Publications

Chakraborty S, Kopitchinski N, Zuo Z, Eraso A, Awasthi P, Chari R, Mitra A, Tobias IC, Moorthy SD, Dale RK, Mitchell JA, Petros TJ, Rocha PP. Enhancer-promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness. Nat Genet. 2023 Feb;55(2):280-290. doi: 10.1038/s41588-022-01295-6. Epub 2023 Jan 30. PMID: 36717694.

Taylor T, Sikorska N, Shchuka VM, Chahar S, Ji C, Macpherson NN, Moorthy SD, de Kort MAC, Mullany S, Khader N, Gillespie ZE, Langroudi L, Tobias IC, Lenstra TL, Mitchell JA, Sexton T. Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus. Genes Dev. 2022 Jun 1;36(11-12):699-717. doi: 10.1101/gad.349489.122. Epub 2022 Jun 16. PMID: 35710138; PMCID: PMC9296009.

Tobias IC, Abatti LE, Moorthy SD, Mullany S, Taylor T, Khader N, Filice MA, Mitchell JA. Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale. Genome. 2021 Apr;64(4):426-448. doi: 10.1139/gen-2020-0104. Epub 2020 Sep 22. PMID: 32961076.

Tobias IC, Kao MC, Parmentier T, Hunter H, LaMarre J, Betts DH. Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases. Stem Cell Res Ther. 2020 Dec 9;11(1):528. doi: 10.1186/s13287-020-02047-1. PMID: 33298190; PMCID: PMC7725121.

Tobias IC, Isaac RR, Dierolf JG, Khazaee R, Cumming RC, Betts DH. Metabolic plasticity during transition to naïve-like pluripotency in canine embryo-derived stem cells. Stem Cell Res. 2018 Jul;30:22-33. doi: 10.1016/j.scr.2018.05.005. Epub 2018 May 17. PMID: 29778974.

Search PubMed for additional publications by Dr. Tobias.