Research Interests

Tan Lab Research

Our lab combines cutting-edge omics tools with 'wet' lab approaches to study transcriptional and post-transcriptional regulation in normal development and its disruption in disease, with the goal of advancing treatments for human infertility and disorders.

Our research interests overlap with the following fields:

• Reproductive biology
• Developmental biology
• Stem cell biology
• RNA biology

 SSC generation and development

Spermatogonial stem cells (SSCs) are adult stem cells in the testis that are essential for spermatogenesis and, hence, male fertility. Like all stem cells, SSCs have the capacity to both self-renew and differentiate. When induced to differentiate, SSCs give rise to subtypes of spermatogenic cells that ultimately generate sperm. There is considerable interest in SSCs as a system to understand stem cell biology and as a therapeutic vehicle for curing male infertility.

One of our laboratory’s research interests is to uncover the cellular and molecular events involved in human and mouse SSC generation and development. To this end, we have employed single-cell RNA sequencing (scRNA-seq) and marker-based strategies to identify these events in human and mouse testicular cells across different developmental stages (Sohni et al., Cell Rep 2019; Tan et al., Dev 2020; Tan et al., PNAS 2020; Capponi et al., manuscript in preparation).

Additionally, we focus on the homeobox transcription factor RHOX10 to explore its transcriptional regulation during SSC genesis and development (Tan et al., Cell Rep 2021; manuscript in preparation). We are also studying how RHOX10 protects the genome by silencing transposable elements (PNAS, 2021). To achieve these goals, we employ a range of omics tools, including RNA-seq, scRNA-seq, CUT&Tag, and SLAM-seq, alongside CRISPR, 'mimic and rescue' approaches, and mouse models.

Our current research is centered on defining the gene networks critical for SSC genesis and development. We will leverage cutting-edge omics tools combined with 'wet' lab approaches to advance these projects.

RNA Turnover Regulation

RNA turnover regulation, a crucial counterpart to transcriptional regulation, plays an essential role in maintaining cellular homeostasis and facilitating dynamic responses to environmental and developmental cues. Despite its importance, studies on RNA turnover regulation are only beginning to grow compared to the extensive research on transcriptional regulation.

I have pioneered studies on RNA turnover and transcriptional regulation during mouse germline specification, identifying distinct regulatory categories and the critical role of RNA turnover in driving germline specification (Nucleic Acids Res, 2022). Our current research focuses on: (i) Utilizing omics tools, including SLAM-seq and scRNA-seq, along with reporter systems and CRISPR, to study the physiological roles of regulated RNA turnover in normal development. (ii) Exploring a specific RNA turnover pathway, nonsense-mediated RNA decay (NMD), to define the roles of the NMD factors in specific developmental contexts.