A photo of Yueh-Chiang Hu.

Yueh-Chiang Hu, PhD


  • Director, Transgenic Animal and Genome Editing Core
  • Associate Professor, UC Department of Pediatrics

About

Biography

I am a genome engineer who leads the highly productive, research-oriented Transgenic Animal and Genome Editing (TAGE) core within the Division of Developmental Biology at Cincinnati Children’s. Using state-of-the-art genome editing and transgenic technologies, we help investigators generate, preserve and recover animal models that further their research.

After joining the TAGE core as the director in 2013, I built the full genome editing service from scratch and continue to develop (or bring in) new tools and technologies. We were one of the first research cores in the nation to switch to CRISPR-based animal production and have continued optimizing our procedures to generate animal and cell models with unprecedented efficiency and speed.

We’ve also expanded our conventional transgenic services to include transgenic and chimeric animal production, cryopreservation, embryo transfer, BAC transgenics, mouse stem cell targeting and mouse recovery via IVF, ICSI or ROSI. In collaboration with the Pluripotent Stem Cell Facility at Cincinnati Children’s, we also established the streamlined hiPS cell gene editing services. Our services are in such high demand that we’ve tripled the size of our team since 2013.

The TAGE core has completed hundreds of genome editing projects, at a pace of one per week, with few failures. One of our key accomplishments was identifying a safe harbor locus near the Col1a1 gene, which is highly accessible for CRISPR-mediated targeting. This finding allowed us to not only create targeted transgenic mice for investigators, but we also used it to build novel mouse tools, including dox-inducible CRISPRi and CRISPRa mice. For example, in one project that incorporated our CRISPR mouse tools, we were able to manipulate the sex development of mice, regardless of the sex chromosome composition, with tetracycline-containing food.

In addition to serving as the TAGE core director, I continue to perform my own independent research. I want to understand the transition point in mid-gestation, where germ cells acquire the competence to enter meiosis and gametogenesis (the uniquely defining characteristics of germ cell lineage). Although we previously found that signals from the genital ridges drive this transition, the identity of the signals remain largely unknown. My research is to identify both the driving factors and the ways germ cells respond to them, utilizing a wide variety of genetic and genomic tools, including the CRISPR mouse tools we have created. Because my own research is taking place within an uncharted area of developmental biology, I aim to produce pioneering knowledge and tools to advance the field.

I enjoy talking and collaborating with researchers outside my field, which has significantly broadened my horizon. My ability to help scientists fulfill their research needs is highly satisfying. Thanks to word of mouth, the TAGE core at Cincinnati Children’s has served academic institutions across the United States.

In 2016, my professional accomplishments earned me a Cincinnati Children’s Faculty Service Achievement Award.

Publications

Pregnancy enables antibody protection against intracellular infection. Erickson, JJ; Archer-Hartmann, S; Yarawsky, AE; Miller, JL C; Seveau, S; Shao, TY; Severance, AL; Miller-Handley, H; Wu, Y; Pham, G; et al. Nature. 2022; 606:769-775.

Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency. Li, CZ; Ogawa, H; Ng, SS; Chen, X; Kishimoto, E; Sakabe, K; Fukami, A; Hu, YC; Mayhew, CN; Hellmann, J; et al. 2022; 4.

Alx1 Deficient Mice Recapitulate Craniofacial Phenotype and Reveal Developmental Basis of ALX1-Related Frontonasal Dysplasia. Iyyanar, PP R; Wu, Z; Lan, Y; Hu, YC; Jiang, R. Frontiers in Cell and Developmental Biology. 2022; 10.

Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation. Hayashi, H; Osaka, S; Sakabe, K; Fukami, A; Kishimoto, E; Aihara, E; Sabu, Y; Mizutani, A; Kusuhara, H; Naritaka, N; et al. Stem Cell Reports. 2021; 16:309-323.

Endogenous retroviruses drive species-specific germline transcriptomes in mammals. Sakashita, A; Maezawa, S; Takahashi, K; Alavattam, KG; Yukawa, M; Hu, Y; Kojima, S; Parrish, NF; Barski, A; Pavlicev, M; et al. Nature Structural Biology. 2020; 27:967-977.

RNA Demethylase ALKBH5 Selectively Promotes Tumorigenesis and Cancer Stem Cell Self-Renewal in Acute Myeloid Leukemia. Shen, C; Sheng, Y; Zhu, AC; Robinson, S; Jiang, X; Dong, L; Chen, H; Su, R; Yin, Z; Li, W; et al. Cell Stem Cell. 2020; 27:64-80.e9.

Generation and characterization of Six2 conditional mice. Li, C; Liu, H; Hu, Y; Lan, Y; Jiang, R. Genesis. 2020; 58.

Genomic Structure, Evolutionary Origins, and Reproductive Function of a Large Amplified Intrinsically Disordered Protein-Coding Gene on the X Chromosome (Laidx) in Mice. Arlt, MF; Brogley, MA; Stark-Dykema, ER; Hu, Y; Mueller, JL. G3: Genes, Genomes, Genetics. 2020; 10:1997-2005.

Functional role of kallikrein 5 and proteinase-activated receptor 2 in eosinophilic esophagitis. Azouz, NP; Klingler, AM; Pathre, P; Besse, JA; Ben Baruch-Morgenstern, N; Ballaban, AY; Osswald, GA; Brusilovsky, M; Habel, JE; Caldwell, JM; et al. Science Translational Medicine. 2020; 12.

Systemic administration of AAV-Slc25a46 mitigates mitochondrial neuropathy in Slc25a46-/- mice. Yang, L; Slone, J; Li, Z; Lou, X; Hu, Y; Queme, LF; Jankowski, MP; Huang, T. Human Molecular Genetics. 2020; 29:649-661.