Woltjen Lab

Stem Cells and Genome Engineering

Research

Lab Research Interests
Human iPS Cells
Reprogramming Mechanisms
Genome Engineering



Lab Research Interests

We aim to develop and adapt cutting edge technologies in genome editing and regulation to promote cellular reprogramming and human health research. To achieve this, we are employing techniques including: transposition, site-specific recombination, nuclease-mediated gene editing, and inducible transgene expression.

Do you want to know MORE? Check out out video on the CiRA YouTube Channel

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.

ウォルツェン准教授は、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手法を研究します。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研究します。この研究は、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が期待されます。

We are hiring researchers at all levels for epigenome editing and analysis to join this new endeavour.

Altos press release HERE

CiRA press release ( JP / EN )

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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.

human iPS cells

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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.

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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).

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