McCormack Group – iPSC-based cell therapies

Key terms: stem cells, developmental biology, regenerative medicine, iPSCs, reprogramming, cell therapy, epigenetics, genome editing, CRISPR, immuno-oncology

Group Leader

Graduate Research Projects

Research goals

  • To develop methods for improved iPSC reprogramming and genome editing
  • To develop therapies that achieve cellular rejuvenation using partial reprogramming
  • To develop iPSC-derived cell therapies for immuno-oncology and regenerative medicine

Research overview

The iPSC-based Cell Therapy group is a collaboration between Monash University and iCamuno Biotherapeutics, an innovative biotech company that is developing cell therapies from induced Pluripotent Stem Cells (iPSCs). Our goal is to understand how adult cells are reprogrammed to iPSCs as well as how to improve these processes and use them for epigenetic rejuvenation of aged or damaged tissues. Secondly, we use improved methods for gene editing and cell differentiation to make novel iPSC-based cell therapies for a range of indications, including Parkinson’s, Ophthalmic diseases, Osteoarthritis and cancer.

Key collaborators

  • Prof Xiaodong Liu (Westlake University)
  • Dr Katerina Vlahos, Dr Sara Howden (Murdoch Institute)
  • A/Prof Angus Johnston, Prof Colin Pouton (Monash University)

Projects

  1. Optimising methods for genome editing and epigenetic reprogramming during iPSC derivation
  2. Hypoimmune editing to avoid immunological rejection of iPSC-derived cell therapies
  3. Development of therapies using partial reprogramming (epigenetic rejuvenation)
  4. Development of cell-based and cell-free therapies from iPSCs

Key publications (A/Prof McCormack)

  1. Abdulla HD, Alserihi R, Flensburg C, Abeysekera W, Luo M, Gray DHD, Liu X, Smyth GK, Alexander W, Majewski IJ, McCormack MP. Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition. J Exp Med 220(6):e20212383, 2023
  2. Abdulla H, Vo A, Shields BJ, Davies TJ, Jackson JT, Alserihi R, Viney EM, Wong NC, Demoen L, Curtis DJ, Alexander WS, Van Vlierberghe P, Dickins R, McCormack MP. T-ALL can evolve to oncogene independence. Leukemia 35:2205-2219, 2021
  3. Jackson JT, Nasa C, Shi W, Huntington ND, Bogue CW, Alexander WS, McCormack MP. A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis. Blood 25(5):803-14, 2015
  4. Shields BJ, Jackson JT, Metcalf D, Shi W, Huang Q, Garnham AL, Glaser SP, Beck D, Pimanda JE, Bogue CW, Smyth GK, Alexander WS, McCormack MP. Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a. Genes and Development 30(1):78-91, 2016
  5. McCormack MP, Young LF, Vasudevan S, de Graaf CA, Codrington R, Rabbitts TH, Jane SM, Curtis DJ. The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science 327(5967):879-83, 2010
  6. McCormack MP, Rabbitts TH. Activation of the T-cell oncogene LMO2 following gene therapy for X-linked Severe Combined Immunodeficiency. New England Journal of Medicine, 350(9):913-22, 2004

Selected publications (Key collaborators)

  1. Liu X, Polo JM. Human blastoid as an in vitro model of human blastocysts. Curr Opin Genet Dev, 84:102135, 2023
  2. Buckberry S*, Liu X*, Poppe D*, Tan JP*, et al. Transient naive reprogramming corrects hiPS cells functionally and epigenetically. Nature, 620:863, 2023
  3. Tan JP, Liu X*, Polo JM*. Establishment of human induced trophoblast stem cells via reprogramming of fibroblasts. Nature Protocols, 17:2739, 2022
  4. Liu X*, Tan JP* et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature, 591:627, 2021
  5. Liu, X*, Ouyang JF*, Rossello FJ* et al. Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature 586:101, 2020
  6. Liu X et al. Comprehensive characterization of distinct states of human naïve pluripotency generated by reprogramming. Nature Methods 14:1055, 2017