Department of Biomedical Sciences (Master's Program in Clinical Trials Assessment)

Lab & Research Interest

My laboratory is interested in studying how cells differentiate into specialized cells with distinct functions. This process, cell differentiation, is critical for embryonic development and adult tissue homeostasis. We study cell differentiation in the context of whole animal, by using the powerful genetic model organism, the fruit fly Drosophila melanogaster. 

      There are two major topics in the lab: (1) the roles of nuclear actin in differentiation of sensory organ precursors (SOPs), the neural precursors of Drosophila peripheral sensory organs. Actin, the major components of cytoskeleton, has recently been demonstrated to play important roles in several basic nuclear processes such as RNA polymerase-mediated transcription, chromatin remodeling, and RNA processing. By combining biochemical and molecular analyses in culture cells as well as genetic and functional analysis in Drosophila, we show that nuclear actin is required for neural precursor differentiation by acting as transcriptional co-factor of bHLH neurogeneic proteins Achaetae and Scute. In the future, we would like to study how the specific association between nuclear actin and Achaetae/Scute is achieved, and how nuclear actin levels might be regulated during neurogenesis and development.

     The second topic in the lab is to study the roles of protein degradation and cell signaling in self-renewal and differentiation of male germline stem cells (GSCs), the adult stem cells that produce gametes throughout the reproductive life of male animals. Our study has shown that BMP signaling, the key regulators of GSC self-renewal, is downregulated as male gonads develop. The downregulation is mediated by the ubiquitin E3 ligase Smurf to control the numbers of GSCs as well as the transit-amplifying cells, the differentiating daughter cells of the GSCs. In the future, we will focus on the regulation of GSC self-renewal and differentiation as well as BMP signaling in GSCs by the stem cell microenvironment. 

Publications

1.          Yun-Ling Hsiao, Hui-Wen Chen, Kuan-Han Chen, Bertrand Chin-Ming Tan, Chia-Hsiang Chen, and Haiwei Pi (2023, February). Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation. Development, accepted. (SCI: 6.862; Rank: 12.8% (5/39) in Developmental Biology). This paper is selected as a “Research Highlight” in Development journal.

2.          Hsun Li, Hsin-Ho Sung, Yi-Chun Huang, Ying-Ju Cheng, Hsiao-Fong Yeh, Haiwei Pi, Edward Giniger, and Cheng-Ting Chien (2022, Sep). Fringe-positive Golgi outposts unite temporal Furin 2 convertase activity and spatial Delta signal to promote dendritic branch retraction. Cell Reports, 40:111372. (SCI: 9.995; Rank: 17% (33/195) in Cell biology)

3.          Pei-Yu Wang, Archan Chakraborty, Hsin-Ju Ma, Jhen-Wei Wu, Anna C.-C. Jang, Wei-Cheng Lin1, Hai-Wei Pi, Chau-Ting Yeh, Mei-Ling Cheng, Jau-Song Yu and Li-Mei Pai (2022, Aug). Drosophila CTP synthase regulates collective cell migration by controlling the polarized endocytic cycle. Development, dev200190. (SCI: 6.862; Rank: 12.8% (5/39) in Developmental Biology)

4.          Yi Chieh Chang, Hsin Tu, To‑Wei Huang, Bo‑Wen Xu & Haiwei Pi* (2020, Jul). Upregulated TNF/Eiger signaling mediates stem cell recovery and tissue homeostasis during nutrient resupply in Drosophila testis. Scientific Reports, 10:11674. (SCI: 4.997; Rank: 25.6% (19/74) in Multidisciplinary Science)

5.          Kun-Yang Lin, Wen-Der Wang, Chi-Hung Lin, Elham Rastegari, Yu-Han Su, Yu-Tzu Chang, Yung-Feng Liao, Yi-Chieh Chang, Haiwei Pi, Bo-Yi Yu, Shu-Hwa Chen, Chung-Yen Lin, Mei-Yeh Lu, Tsu-Yi Su, Fei-Yang Tzou, Chih-Chiang Chan & Hwei-Jan Hsu (2020, Jun). Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling. Nature Communications, 11:3147. (SCI: 17.694; Rank: 8% in Multidisciplinary Science).

6.          Yi Chieh Chang, Hsin Tu, Jing-Yi Chen, Ching-Chin Chang, Shu Yuan Yang, Haiwei Pi* (2019, Jul). Reproduction disrupts stem cell homeostasis in testes of aged male Drosophila via an induced microenvironment. PLOS Genetics, 15 (7): e1008062. (SCI: 6.02; Rank: 15.4% in Genetics and Heredity). This paper is featured in PLOS Genetics by an accompanying Perspective article “ Irreversible effects of youthful choices in aged adults”.

7.          Yang SY*, Chang YC, Wan YH, Whitworth C, Baxter EM, Primus S, Pi H, Van Doren M*. (2017, Aug). Control of a Novel Spermatocyte-Promoting Factor by the Male Germline Sex Determination Factor PHF7 of Drosophila melanogaster. GENETICS, 206(4),1939-1949. (SCI: 4.4; Rank: 32% (56/175) in Genetics and Heredity)

8.          Chien-Hsiang Wang, Yi-Chun Huang, Pei-Yi Chen, Ying-Ju Cheng, Hsiu-Hua Kao, Haiwei Pi, Cheng-Ting Chien (2017, May). USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin. eLife, 10(6),e26886. (SCI: 8.713; Rank: 8.5% (8/94) in Biology)

9.          Shih-Han Kao, Chen-Yuan Tseng, Chih-Ling Wan, Yu-Han Su, Chang-Che Hsieh, Haiwei Pi, and Hwei-Jan Hsu (2015, Feb). Aging and insulin signaling differentially control normal and tumorous germline stem cells. Aging Cell, 14(1): 25–34. (SCI: 11.005; Rank: 15.3% (30/195) in Cell Biology)

10.      Yi-Chun Huang,Yu-Nung Lu,June-Tai Wu,Cheng-Ting Chien, Haiwei Pi* (2014, Nov). The COP9 Signalosome Converts Temporal Hormone Signaling to Spatial Restriction on Neural Competence. PLOS Genetics, 10(11),1-13. (SCI: 6.02; Rank: 15.4% in Genetics and Heredity)

11.      Yun-Ling Hsiao, Yu-Ju Chen, Yi-Jie Chang, Hsiao-Fong Yeh, Yi-Chun Huang and Haiwei Pi (2014, Jan). Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs. Journal of Cell Science, 127:182-90.