Animal bodies are composed of various types of tissues and cells that perform physiological functions animals need in order to stay vital.  The development of an animal is therefore also the development of tissues and cells within an animal body.  In mammals, all lives start with the fusion of two highly specialized gametes, sperm and egg, in the process of fertilization that generates totipotent cells, the zygotes, which can develop into all tissue and cell types of the future animal.  Genetic defects occurred during gametes and embryo development can influence adult animals, and in human, cause human diseases.  Thus, studies of development of gametes and early embryos will not only help to understand fundamental biological questions but also provide us with better chances to conquer human diseases.

The overall research in my lab is to understand the developmental mechanisms of male gamete, the sperm, using mouse as the model system.  By applying different biological approaches, we aim to understand the molecular basis that underlies the development of mouse spermatozoa, mechanisms that control spermatogenesis.  In the meantime, regulation of pre-implantation embryogenesis and the relationships between early embryogenesis and the future development of animals are another line of our focus.  Insights gained from these studies will help to solve fundamental questions in developmental biology and open new windows for finding treatments of human diseases.

Our current research includes:

1) Molecular mechanisms that regulate mouse spermatogonial stem cells.  Spermatogonial stem cells give rise to mature spermatozoa throughout the adult life of an animal.  It is an ideal model to study stem cell biology and regeneration.  Using biochemical and cell biological approaches, as well as contemporary genetic and high-throughput methods, we wish to first learn the true identities of spermatogonial stem cells in their natural habitats and subsequently to dissect the molecular pathways that govern their maintenance and differentiation throughout the life of an animal, even during the regeneration when spermatogenic cells are injured by un-natural means.  We are currently investigating the roles of RNA binding proteins, AKT-mTORC1/2 signaling and translation regulatory pathways that may influence the self-renewal and proliferation of spermatogonial stem cells.  Some of the target genes are identified from gene expression profiling of mouse spermatogonial stem cells we conducted previously.

2) Translational regulation during spermiogenesis.  Post-meiotic development occupies one-third of spermatogenic process and proceeds without much active gene transcription.  The spatial-temporal regulation of protein synthesis that is required for sperm differentiation is a central mechanism that governs sperm development.  Through the study of sperm-specific proteins such as AKAP3, we wish to understand the molecular underpinnings that direct the regulatory signaling and molecular mechanisms that govern spermiogenesis as a whole. 

3) Molecular mechanisms of germ cell development share their roots at the beginning of animal’s life.  The analyses on molecular and cellular differentiation of pre-implantation embryos will bring us insights into how cells change their identities during development in order to fulfill physiological functions. 

These works are the necessary and first steps toward our future endeavors in understanding how animals utilize reproductive systems to perpetuate and improve lives and eventually comprehending the nature of our own.