The Tissue and Disease Modelling Core (TDMC) at the BC Children’s Hospital Research Institute offers rapid generation of induced pluripotent cells (iPSCs) from patient blood samples and editing of the genome of these iPSCs. This facility also offers training to users on the proper culture of pluripotent cells and their differentiation towards various lineages.

The TDMC enables researchers to access powerful iPSC and genome editing technology to determine the biological mechanisms of disease in patients, and use disease models, built from patient cells, to inform diagnosis and therapeutic strategies.

Dr. Francis Lynn, oversees the scientific and technical operations of the iPSC arm at TDMC, and he has proven expertise in iPSC and genome editing technology. 

Notable iPSC-related publications that were catalyzed by the TDMC include:

Biggs, C.M., Cordeiro-Santanach, A., Prykhozhij, S.V., Deveau, A.P., Lin, Y., Del Bel, K.L., Orben, F., Ragotte, R.J., Saferali, A., Mostafavi, S., Dinh, L., Dai, D., Weinacht, K.G., Dobbs, K., Ott de Bruin, L., Sharma, M., Tsai, K., Priatel, J.J., Schreiber, R.A., Rozmus, J., Hosking, M.C., Shopsowitz, K.E., McKinnon, M.L., Vercauteren, S., Seear, M., Notarangelo, L.D., Lynn, F.C., Berman, J.N., & Turvey, S.E. (2022). Human JAK1 gain of function causes dysregulated myelopoeisis and severe allergic inflammation. JCI Insight, 7(24).

Deen, M.C., Zhu, Y., Gros, C., Na, N., Gilormini, P.A., Shen, D.L., Bhosale, S., Anastasi, N., Wang, R., Shan, X., Harde, E., Jagasia, R., Lynn, F.C., & Vocadlo, D.J. (2022). A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebrosidase activity within live cells. Proceedings of the National Academy of Sciences, 119(29), e2200553119.

Frew, J., Baradaran-Heravi, A., Balgi, A.D., Wu, X., Yan, T.D., Arns, S., Shidmoossavee, F.S., Tan, J., Jaquith, J.B., Jansen-West, K.R., Lynn, F.C., Gao, F.B., Petrucelli, L., Feldman, H.H., Mackenzie, I.R., Roberge, M., & Nygaard, H.B. (2020). Premature termination codon readthrough upregulates progranulin expression and improves lysosomal function in preclinical models of GRN deficiency. Molecular Neurodegeneration, 15(1), 21.

Krentz, N.A.J., van Hoof, D., Li, Z., Watanabe, A., Tang, M., Nian, C., German, M.S., & Lynn, F.C. (2017). Phosphorylation of NEUROG3 links endocrine differentiation to the cell cycle in pancreatic progenitors. Developmental Cell, 41(2), 129–142.e6.

Dr. Mahmoud Pouladi leads the scientific and technical operations of the genome editing division at TDMC, ensuring the development and implementation of advanced genome engineering strategies. 

Dr. Pouladi has made significant contributions to genome editing, particularly in the context of neurodevelopmental and neurodegenerative disorders. His research utilizes CRISPR/Cas9 and other genome engineering tools to develop therapeutic strategies for diseases such as Huntington’s disease and Fragile X syndrome. Notable publications include:

Ooi, J., Langley, S.R., Xu, X., et al. (2019). Unbiased Profiling of Isogenic Huntington Disease hPSC-Derived CNS and Peripheral Cells Reveals Strong Cell-Type Specificity of CAG Length Effects. Cell Reports, 26(9), 2494-2508.e7.

Xu, X., Tay, Y., Sim, B., et al. (2017). Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells. Stem Cell Reports, 8(3), 619–633.

Utami, K.H., Skotte, N.H., Colaço, A.R., et al. (2020). Integrative Analysis Identifies Key Molecular Signatures Underlying Neurodevelopmental Deficits in Fragile X Syndrome. Biological Psychiatry, 88(7), 500–511.

Basic iPSC Service

Within three months the TDMC can generate of 3 iPSC clones from PBMCs (~0.5ml of blood). Included in this service is basic characterization with genetic analysis for chromosome abnormalities.

Genomic Editing Service

Genome editing projects typically take 3–6 months, depending on the complexity of the requested modifications. The service includes:

  • Design and validation of genome editing strategy (e.g., CRISPR/Cas9, base editing).
  • Transfection and selection of modified iPSC clones.
  • Screening and validation of genome edits using sequencing and other molecular techniques.

Project Requirements:

To initiate a genome editing project, researchers must provide:

  • Well-characterized iPSC lines (or request TDMC to generate iPSCs before editing).
  • Details on the target gene(s) and desired modifications (knockout, knock-in, point mutation, etc.).
  • Ethics approval (if applicable).

Project Inquiries

For project requests, please complete the TDMC Project Intake Form below.

TDMC Project intake form

For more information on services and pricing, contact:

Momina Masud – momina.masud@ubc.ca