Professional Experiences

2018/08-2022/07 New York University, School of Medicine, Department of Biochemistry & Molecular Pharmacology (Postdoctoral fellow).

2017/08-2018/07 NIH, National Cancer Institute (Visiting fellow).

2015/02-2016/07 Academia Sinica, Institute of Cellular and Organismic Biology (Postdoctoral fellow).

2010/09-2015/01 National Defense Medical Center, Graduate Institute of Life Sciences (Ph.D.)

Research interests 

Background

Stem cells are housed in niches, specialized microenvironments that provide physical contact and secrete short-range self-renewal cues. It is well-established that somatic stem cells compete for limited space in the niche, but the factors that regulate competition between germline stem cells (GSCs) are largely unknown. Elucidating the molecular mechanisms controlling stem cell competition have great potential to improve cancer therapeutics and regenerative medicine.

The Drosophila testis is an excellent model for studying stem cell competition because of the ease of manipulation and the powerful genetics available in flies. All cell types can be identified unequivocally. In the testis, a quiescent niche supports GSCs, which divide asymmetrically to produce a GSC daughter and a gonialblast (Gb) that differentiates into mature sperm (Fig. 1). During my postdoc, I identified the transcription factor Chinmo as a critical regulator of competition between GSCs [1]. I showed that a GSC homozygous for a mutation in chinmo outcompetes neighboring wild-type (WT) GSCs for niche access (Fig. 2B). Overtime all, WT GSCs are expelled from the niche, resulting in testes with a GSC pool comprised exclusively of chinmo-/- GSCs (See the detailed mechanism in Fig.2).

Our data uncover a novel mechanism of stem cell competition in which the competitive stem cell alters the niche environment to benefit itself and its descendants. Three research directions were proposed to address these questions to understand how chinmo and what direct targets of chinmo are involved in stem cell competition and aging.

Research direction

1.Identifying Chinmo target genes that are involved in GSC competition.

Chinmo contains an N-terminal BTB domain and two C-terminal Zinc-finger domains and is thought to function as a transcription factor. However, no direct Chinmo target genes have as yet been identified. In this proposal, we will endogenously tag chinmo at its N-terminal and identify chinmo immediate target genes by performing ChIP-seq experiments using testicular lysates. Next, we will see the identity and characterize if the Chinmo target genes promote GSC competition and moat formation.

2.Determine the factors that regulate the expression of chinmo mRNA in GSCs.

I demonstrated that the level of Chinmo protein in WT GSCs progressively decreased during aging. Testes from aged WT males displayed a moat comprised of Pcan and Lan and significantly reduced number of GSCs (Fig. 3) [1]. I showed that increasing the level of Chinmo in GSCs throughout adulthood significantly inhibited the formation of the moat and restored the number of GSCs [1]. These data indicate that the status of Chinmo in GSCs is critical to tissue homeostasis during aging. This project aims to identify the factors that cause the downregulation of Chinmo protein in GSCs during aging. RNA-binding proteins (RBPs) are involved in multiple levels of mRNA regulation; we will survey RBPs consensus sequence from chinmo mRNA and test whether predicted RBPs are expressed in GSCs. Next, we will perform a small-scale RNAi screen to examine if predicted RBPs in GSCs regulate Chinmo protein expression during aging.

3.Identifying the factors that allow GSCs to remain in old niches.

I showed that chinmo-/- GSCs and aged GSCs (that have a low level of Chinmo) share similar phenotypes (Fig. 3). These data indicate that stem cell competition subverts an aging mechanism to pass their DNA content to the next generation. Identifying genes gives GSCs a competitive advantage for niche access during aging. We will systemically compare and analyze the transcriptome from young and aged GSCs. Then, we will characterize the up/downregulated genes from aged GSCs for GSC homeostasis.

You will learn (1) Fly genetics and development, (2) Stem cell and aging biology (3) Basic bioinformatics and molecular technique from our lab’s training.

Undergraduate or graduate students passionate and motivated in stem cell and aging biology are welcome. If you have any questions, please don’t hesitate to contact me by email or directly visit my office at #912.

Reference

1. Tseng, C.Y., et al., chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche. Dev Cell, 2022. 57(1): p. 80-94 e7.

Honor 

2009 Honorary Member of Phi-Tau-Phi Scholastic Honor Society of R.O.C.

2015 Thesis Award, Tang-der Lee Biomedical Foundation

2019-2021 NYSTEM postdoctoral fellowship

Course 

Molecular Biology (MS)

Advanced Molecular Biology (MS)

Methods in Molecular Biology

Seminar

Review of Current Literature

Advanced Molecular Genetics

Basic stem cell biology

The Vitality and Sustainability of Life