Research
The Woltjen Lab develops and deploys cutting-edge gene-editing technologies in iPSCs to study and gain “total control of the human genome”. Our goal is to understand the genome and master techniques required to correct mutations and append new gene functions. Towards this goal, the Woltjen Lab developed methods to precisely edit single-nucleotides and create deletions, the two most common classes of pathogenic human genetic variants. Furthermore, we are establishing precise editing of repetitive DNA sequences which are highly variable throughout human evolution and amongst individuals. Our research addresses significant technical hurdles towards understanding genome function.
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New Research
Based on our prior experience in somatic cell reprogramming mechanisms and in vivo reprogramming, we are leading one of 4 new projects in CiRA funded by Altos Labs on cellular rejuvenation programming. The Woltjen Lab project is titled “Manipulation of aging through refined epigenetic reprogramming.”
The project will employ a multi-omics approach to study age-related epigenetic changes, and develop cutting-edge epigenome editing tools to refine cellular reprogramming for rejuvenation. With our collaborators, we will make use of unique in vitro models of rapidly aging cells from the thymus and placenta. We aim to establish refined reprogramming systems that provide improved tissue function, efficient self-healing, and safe regenerative medicine applications.
ウォルツェン研究室は、Altos LabsとCiRAが共同で行うiPS細胞関連技術を用いた老化研究の4プロジェクトのうち、1つを担当しています。現在は精密なエピジェネティック・リプログラミングを用いた細胞老化の操作やマルチオミクス解析を用いて、胸腺の細胞や胎盤の細胞が急激に老化するプロセスでおこる固有のエピジェネティックな変化を解析しています。最終的に、「組織の機能改善、効率的な自己治癒、安全な再生医療応用を可能にする初期化システムの開発に貢献すること」を目標に研究を進めています。
We are hiring researchers at all levels for epigenome editing and analysis to join this new endeavour.
Human Induced Pluripotent Stem (iPS) Cells
In 2007, Kyoto University researchers Drs. Takahashi and Yamanaka demonstrated that human skin cells could be reprogrammed back to a pluripotent embryonic state. As induced pluripotent stem (iPS) cells may be derived from any donor, this technology makes the promise of patient-tailored diagnostics and therapeutics a tangible prospect; revolutionizing the way we perceive regenerative medicine.
Through iPS cell reprogramming, we may capture a particular genotype, and even engineer it (if need be) to correct mutations leading to genetic disease. Using methods learned from developmental biology to coax the cells into specialized derivatives, we may model diseases or screen for drug effects in vitro. Before iPS cell-based clinical therapies are achieved, these pre-clinical tests will provide a deeper understanding of human health.
Somatic Cell Reprogramming Mechanisms
Reprogramming somatic cells to induced pluripotent stem (iPS) cells through ectopic expression of four transcription factors is a profound technology of which little is known mechanistically. Elucidating the key requirements in the process will improve iPS cell quality and consistency, providing biological insight into cellular plasticity. Using a drug-inducible reprogramming system, we are dissecting the kinetics of early reprogramming. Our goal is to reveal changes that can be applied to augment current reprogramming standards.
Cell Reprogramming and Differentiation
As a post-doctoral fellow, Dr. Woltjen developed a novel non-viral approach to iPS cell production (Woltjen et al., Nature 2009; Kaji et al., Nature 2009). The method used piggybac (PB) transposons from Trichoplusia ni (cabbage looper moth). Transposons integrate into the genome to achieve high-efficiency transgenesis. Moreover, as “jumping genes” they can be re-mobilized and removed from the genome. This property allowed us to generate the first footprint-free human iPS cells. We have continued to use PB to study reprogramming mechanisms and induce differentiation into muscle cells (Tanaka et al., 2013) or neurons (Kondo et al., 2017). Some of our most popular PB transposons are available from Addgene (Kim et al., 2016).
