A fascinating feature of embryonic development is the reproducibility of temporal developmental programs (e.g., somite and limb formation) among individuals of the same species. Between different species, however, developmental timing varies drastically; human gestation is roughly 40 weeks, while mice require only 3 weeks. Remarkably, the differentiation rate of human and mouse pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, recapitulates species-specific timing (mouse PSCs differentiate much faster than human PSCs). This suggests that, without normal developmental cues from an intact embryo, a largely unknown intrinsic timing mechanism exists in PSCs in vitro. My long-term research interest is to understand the developmental timing mechanisms that control cell fate during differentiation and embryonic development.
Areas of Expertise
- Pluripotent stem cell biology, cellular reprogramming and regeneration.
- Human endoderm and urogenital development and disease modeling.
- Gene oscillation and molecular clock works.
- Single-cell and bulk RNA-seq analyses on temporal cell state transition.
- CRISPR/Cas9 mediated knockin or knockout of mouse and human pluripotent stem cells.
Ph.D. Cellular and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
B.S. Zoology, National Taiwan University, Taipei, Taiwan.
- Presentation Award, Center of Cell & Gene Therapy Conference, Houston, TX.
- Claude W. Smith Fellowship Award. Baylor College of Medicine.
- Dean’s Award at National Taiwan University.
- Da-qui Chei & Dr. Song-yen Fong Memorial Scholarship.
- Undergraduate Research Scholarship. National Taiwan University.
First-Author Peer-Reviewed Publications
- Bacher R*, Chu LF*, Leng N, Gasch A, Newton M, Thomson JA, Stewart R, and Christina Kendziorski. SCnorm: A quantile-regression based approach for robust normalization of single-cell RNA-seq data. Nature Methods. 2017; PMID: 28418000. *Co-first author
- Chu LF†*, Leng N*, Zhang J, Hou Z, Mamott D, Vereide DT, Choi J, Kendzrioski C, Stewart RM, Thomson JA†. Single-cell RNA-seq reveals novel regulators of human embryonic stem cells differentiation to definitive endoderm. Genome Biology. 2016; PMID: 27534536.†Co-corresponding author, *Co-first author
- Leng N*, Chu LF*, Barry C, Li Y, Choi J, Li X, Jiang P, Stewart RM, Thomson JA Kendzrioski C. Oscope identifies oscillatory genes in unsynchronized single cell RNA-seq experiments. Nature Methods. 2015; PMID: 26301841. *Co-first author
- Chu LF, Surani MA, Jaenisch R, Zwaka TP. Blimp1 expression predicts embryonic stem cell development in vitro. Current Biology. 2011; PMID: 22000107. Recommended by Faculty of 1000.
- Chu LF and Zwaka TP. “Human Pluripotent Cells: The Biology of Pluripotency”. Human Stem Cell Technology and Biology: A Research Guide and Laboratory Manual (2011). Chapter 26. 313-325.
Co-Author Peer-Reviewed Publications
- Joseph DB, Chandrashekar AS, Abler LL, Chu LF, Thomson JA, Mendelsohn C, Vezina CM In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells. Proceedings of the National Academy of Sciences. 2018 (in press)
- Vermillion KL, Bacher R, Tannenbaum AP, Swanson S, Jiang P, Chu LF, Stewart R, Thomson JA, and Vereide DT. Novel Spatial Patterns of Gene Expression are Revealed in the Chick Primitive Streak by Ordering Single Cell Transcriptomes. Developmental Biology. 2018. PMID:29678445.
- Phillips MJ, Jiang P, Howden S, Barney P, Min J, York NW, Chu LF, Capowski EE, Cash A, Jain S, Barlow K, Tabassum T, Stewart R, Pattnaik BR, Thomson JA, Gamm DM. A novel approach to single cell RNA-seq analysis facilitates in silico gene reporting of human pluripotent stem cell-derived retinal cell types. Stem Cells. 2017, PMID:29230913.
- Zhang J, Chu LF, Hou Z, Schwartz MP, Hacker T, Vickerman V, Swanson S, Leng N, Nguyen BK, Elwell A, Bolin J, Brown ME, Stewart R, Burlingham WJ, Murphy WL, Thomson JA. Functional characterization of human pluripotent stem cell-derived arterial endothelial cells. Proceedings of the National Academy of Sciences. 2017; PMID:28696312.
- Korthauer K, Chu LF, Newton MA, Li Y, Thomson JA, Stewart R and Kendziorski C. scDD: A statistical approach for identifying differential distributions in single-cell RNA-seq experiments. Genome Biology. 2016; PMID:27782827.
- Lee WH, Higuchi H, Ikeda S, Macke E, Takimoto T, Pattnaik B, Liu C, Chu LF, Siepka SM, Krentz KJ, Rubinstein D, Kalejta RF, Thomson JA, Mullins R, Takahashi JS, Pinto L, Ikeda A. Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies. 2016; PMID:27863209.
- Leng N, Choi J, Chu LF, Thomson JA, Kendziorski C, Stewart R. OEFinder: A user interface to identify and visualize ordering effects in single-cell RNA-seq data. Bioinformatics. 2016; PMID:26743507.
- Stewart R, Rascón CA, Tian S, Nie J, Barry C, Chu LF, Ardalani H, Wagner RJ, Probasco MD, Bolin JM, Leng N, Sengupta S, Volkmer M, Habermann B, Tanaka EM, Thomson JA, Dewey CN. Comparative RNA-seq analysis in the unsequenced axolotl: the oncogene burst highlights early gene expression in the blastema. PLoS Computational Biology. 2013; PMID: 23505351.
- Vereide DT, Vickerman V, Swanson SA, Chu LF, McIntosh BE, Thomson JA. An expandable, inducible hemangioblast state regulated by fibroblast growth factor. Stem Cell Reports. 2014; PMID: 25458896.
- Hou Z, Zhang Y, Propson NE, Howden SE, Chu LF, Sontheimer EJ, Thomson JA. Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proceedings of the National Academy of Sciences. 2013; PMID:23940360.
- Dejosez M, Krumenacker JS, Zitur LJ, Passeri M, Chu LF, Songyang Z, Thomson JA, Zwaka TP. Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells. Cell. 2008; PMID:18585351.
- Shah R, Medina-Martinez O, Chu LF, Samaco RC, Jamrich M. Expression of FoxP2 during zebrafish development and in the adult brain. International Journal of Developmental Biology. 2006; PMID: 16525940.