The Lei lab studies ovarian biology and female reproductive aging. We are interested in addressing how the biological clock of ovarian aging is set initially, with particular attention to the following three significant questions in ovarian biology:
- Why do over 99% of oocytes undergo cell death and are never used throughout a female reproductive lifespan?
- How do oocytes become quiescent during oocyte formation in the fetal ovary and how do oocytes remain quiescent in the adult ovary for decades?
- What is the fundamental difference between young and aged oocytes?
We use mouse genetics, single-cell biology, advanced imaging, as well as molecular and biochemical approaches to study these questions. In collaboration with physicians, knowledge acquired in the lab is applied to ovarian health issues within clinical setting.
Why it matters
In females, oocytes that form during fetal ovarian development, namely ovarian reserve, serve as the only source for egg production and sustaining ovarian function in adulthood. A lingering mystery of mammalian oogenesis is large-scale germ cell death. For example, although a baby girl has over 1 million oocytes in her ovaries, a majority of the oocytes remain quiescent or undergo cell death gradually. On average, a woman only ovulates about 500 eggs throughout her entire reproductive lifespan. Moreover, oocytes are very vulnerable to factors, such as aging, radiation, and chemotherapy. Drastic declines in oocyte quality and quantity in young/middle age women lead to a significantly increased chance of infertility and birth defects. Uncovering the mechanisms underlying oocyte formation, oocyte quiescence, and oocyte death will allow us to better understand ovarian health issues.
Understanding to how the ovarian reserve forms during fetal development and is maintained in adulthood is the foundation for elucidating age-associated reproductive issues in females. This fundamental knowledge will enable us to develop novel precision medical solutions to female reproductive issues, and to improve female reproductive health and overall life quality.
Lei Lei, PhD
Dr. Lei is an associate professor and the scientific director of the Center for Female Reproductive Longevity and Equality (CFRLE) at the Buck Institute. Dr. Lei received her postdoctoral trainings in ovarian biology in the Feinberg School of Medicine, Northwestern University, where she studied the role of microRNAs in folliculogenesis and hormonal interactions during ovarian follicle assembly. Dr. Lei further conducted research as a postdoctoral research associate at the Department of Embryology, Carnegie Institution for Science. During this time, Dr. Lei worked together with Dr. Allan Spradling and developed single-cell lineage tracing in the mouse model. By using this powerful approach, Dr. Lei elucidated the lack of oogonial stem cells in adult female mice and discovered that mouse oocytes form by collecting cytoplasmic content from sister fetal germ cells. This discovery provides novel insights into the biology of mammalian oocyte formation. Before joining the Buck, Dr. Lei was an assistant professor in the University of Michigan Medical School. Currently, Dr. Lei serves as review editor for the journals Biology of Reproduction and Frontiers in Endocrinology. The Lei lab received the Young Investigator Achievement Award from the Jones Foundation for Reproductive Medicine and NIH R01award.
Lauren Haky Research Associate
Lauren received her undergraduate degree in biology from Willamette University in Salem, Oregon. In an undergraduate laboratory, she participated in a collaborative large scale mutagenetic screen using Drosophila melanogaster to target the Actin Depolymerizing Factor and cofilin ortholog slingshot. During the summer of 2019, she interned for DuPont Nutrition & Biosciences where she expressed novel fusion proteins. In her free time Lauren enjoys to paint, go on hikes with her corgi pup, Daisy, and debate art history theories.
Kanako Ikami, PhD Postdoctoral Research Fellow
Kanako received her BA degree in pharmacy from Kyoto Pharmaceutical University in Japan 2008 and her Ph.D. from National Institute for Basic Biology in Japan in 2014. During her PhD . Kanako studied mechanism of spermatonial stem cell maintenance during mouse spermatogenesis. Kanako joined the Lei lab at the University of Michigan in 2015 and has been working on cell fate determination during oocyte formation. Kanako received several awards during her postdoc time, including the fellowships from Toyobo Biotechnology Foundation, The Uehara Memorial Foundation and the Japan Society for the Promotion of Science. During her free time, Kanako likes to play tennis and piano.
Doyle Lokitiyakul PhD Candidate, Buck-USC Biology of Aging Program
Doyle received his undergraduate BA degree in Biology from Washington University in St. Louis. Currently, he is a graduate student from the University of Southern California-Buck Biology of Aging Ph.D. program, joining the Lei lab in July 2020. As an undergrad, his main focus was on NAD+ and its regulatory effects on the aging process. During his undergraduate project, he participated in a CRISPR Cas9 screen, aiming to determine which protein was responsible for a sudden decrease in NAD levels within macrophages during inflammation: a phenomenon that is hypothesized to contribute to age related inflammation. Currently, as a member of the Lei lab, he is interested in studying how oocytes maintain their molecular integrity and functions with age. During his free time Doyle enjoys reading long science fiction/epic fantasy novels and practicing Muay Thai.
Ronald Pandoy Research Associate and Administrative Lab Manager
Ronald received a BS degree in physiology from the University of California, Santa Barbara in 2010. After working for several years, he decided to expand his education and obtained an additional BS degree in biomedical science from La Sierra University in 2016. Upon completing his additional degree, Ronald enrolled at Walla Walla University to pursue a MS degree in biology. There, he completed his thesis in 2019 which focused on protein degradation pathways in the social amoeba Dictyostelium discoideum. Ronald joined the Buck in August 2019. In his spare time, Ronald enjoys all manners of sports and games.
Hao Yan, PhD Postdoctoral Research Fellow
Dr. Yan Grew up in Sichuan, China and obtained his bachelor’s degree in bio-engineering in Southwest Jiaotong University in China. After that, he studied ovary development in mice at China Agricultural University and received his PhD degree in physiology in June 2018. The research was focused on the understanding of mechanisms of non-renewable primordial follicle formation, maintenance and activation in mammal. Hao joined the Lei lab in August 2019 where he continues to pursue his research interest of ovary development and aging. Hao likes badminton and fishing.
- Larose H, Shami AN, Abbott H, Manske G, Lei L*, Hammoud SS* (2019) Gametogenesis, a journey from inception to conception. Current Topics in Developmental Biology: Organ Development.
- Pepling M*, Lei L* (2018) Germ cell nests and germline cysts. Encyclopedia of Reproduction, Volume 3- Gametogensis, Fertilization and Early Development.
- Ikami K, Nuzhat N, Lei L* (2017) Organelle transport during mouse oocyte differentiation in germline cysts. Current Opinion in Cell Biology 44:14-19.
- Lei L*, Spradling AC* (2016) Mouse oocytes differentiate through organelle enrichment from sister cyst germ cells. Science 352(6281): 95-99. (F1000Prime recommended)
- Lei L, Spradling AC (2013) Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proceedings of the National Academy of Sciences of the United States of America 110(21): 8585-8590.
- Lei L, Spradling AC (2013) Mouse primordial germ cells produce cysts that partially fragment prior to meiosis. Development 140(10): 2075-2081.