CSCI Visitor Seminar - Prof. Yen Choo

Speaker: Professor Yen Choo, PhD - Associate Professor of Stem Cell Science and Regenerative Medicine | Lee Kong Chian School of Medicine

Title: "A combinatorial screening platform to discover gene regulatory networks for rational reprogramming of cellular identity"

Host: Yizhou Yu

This event will be in person with no online registering required.
 

Abstract:
Cellular plasticity enables reprogramming of cell identity through ectopic expression of transcription factors (TFs) that induce and stabilize gene regulatory networks (GRNs) specifying discrete cellular states. For example, transient expression of the Yamanaka factors stably reprograms diverse cell types to iPSCs; and these in turn can be programmed into different, more developed, lineages using further TF cocktails. However, identification of optimal TF combinations for cell reprogramming remains a challenge, mainly because current screening methods are highly multiplexed and difficult to deconvolute, and because the widely used ‘n-1 deconvolution’ strategy reveals only a single (possibly suboptimal) GRN. Even if TF switches can be identified, the circuitry of these components remains obscure since TF expression is not temporally resolved in such screens. We have developed a versatile high throughput screening method to test all possible combinations and permutations of (2, 3, 4… n) TFs from a predetermined subset, to discover functional TF combinations and to resolve the order/timing in which they orchestrate reprogramming. We will present screens covering up to 10,000 combinations of TFs from a predetermined set of up to 20 TFs, delivered using lentivirus or as mRNA, to discover new lineage control switches that reprogram iPSCs into megakaryocytes and erythroblasts, and iPSC-derived pancreatic progenitors into pancreatic beta cells. We believe this platform technology will be widely applicable to cell reprogramming in general, where the ability to rationally map out genetic circuits determining cell identity will enable diverse applications in fields ranging from synthetic biology to regenerative medicine.

Short Bio:
Yen Choo is Associate Professor of Stem Cell Science and Regenerative Medicine at Lee Kong Chian School of Medicine (LKC Medicine), a joint medical school of Singapore’s Nanyang Technological University (NTU) and Imperial College London. He is also Executive Director of co11ab@Novena, a BioMedtech incubator established jointly between NTU, the National Healthcare Group (HNG) and the Agency for Science, Technology and Research (A*STAR).

In addition to his academic career, Prof. Choo is a serial entrepreneur with over 25 years of CEO/CSO operational experience in biotechnology companies developing advanced therapies. He was the founder and CSO of Gendaq (merged with Sangamo Therapeutics), the biotech company that developed the zinc finger protein technology used in genome editing. He is the founder and Chairman of Plasticell, one of the UK’s pioneering regenerative medicine companies using combinatorial screening technologies to develop stem cell therapies. He also founded Progenitor Therapeutics, a joint venture with GSK to discover small molecule drugs that regenerate tissues of the human body.

Prof. Choo sits on the Steering Committee for the UK Stem Cell Bank and for the Use of Stem Cell Lines, which oversees UK embryonic stem cell research and the UK Stem Cell Bank. He also serves on the board of the Advanced Cell Therapy and Research Institute, Singapore (ACTRIS), a GMP facility established for process development and manufacturing of cell-based therapeutics.

His research, inventions and companies have been recognised by prizes including The Queen’s Award in Enterprise for Innovation, The Scientist Top 10 Innovations and the GE Healthcare and Science Prize for Young Scientists.

He holds a PhD in Molecular Biology from the University of Cambridge, for the ‘Design of site-specific DNA binding proteins’, work carried out at the MRC Laboratory of Molecular Biology together with Aaron Klug.