With a great interest on women’s reproduction health, Dr. Nan Zhang joined the Woodruff Lab in 2014. He earned a PhD degree from University of Massachusetts at Amherst in the lab of Dr. Rafael Fissore in 2012. His doctoral thesis focused on the regulation of calcium signaling in mammalian eggs. In his Ph.D study, Dr. Zhang has made original contributions of major significations to the field of reproductive science, including but not limited to investigations on the mechanisms by which sperm prompts the activation and development of mammalian cells, the regulation of IP3R1 during maturation and fertilization, the effects of defective calcium signaling in aging populations (3-9). Since he joined Woodruff lab, Dr. Zhang has been studying the zinc signaling during maturation and fertilization in mouse. He is also trying to translate the zinc spark technology from mouse to human and investigating gametes dynamics with the goal of improving fertility outcome in human. His current work has resulted in many important discoveries on the Non-Invasive test of eggs developmental potential, which is fully funded by Ferring Pharmaceuticals. Two of his most recent publications in Scientific Reports show that profiles of Zn sparks are correlated with embryo development and have a great potential to be used as a biomarker of embryo quality in human medicine (1,2). In one study, he and his colleagues found that zinc fireworks actually occur when a human egg cell is activated by sperm enzyme (Figure 1). In another study using mouse model, he discovered that the zinc spark is a robust marker of egg quality (Figure 2). In this study, Dr. Zhang managed to capture the moment when a sperm enters an egg in real time followed by a radiant zinc release (Figure 3). The discoveries have received enthusiastic media coverage and resulted in financial support from Ferring Pharmaceuticals for the 2nd phase of his research. Dr. Zhang’s current research aims at developing these discoveries into applicable technologies in human medicine. To extend the Zn2+ project, he also applied the Zn2+ technology to investigate the fertility threats caused by harmful factors including cancer treatment and ageing.
Figure 2. Embryo development is correlated with the intensity of zinc sparks. Max intensity capture of Zn sparks induced by 5 μM Ca-Ionomycin. The developmental fate of each egg was tracked and annotated.
1. Zhang N, Duncan FE, Que EL, O’Halloran TV and Woodruff TK (2016). The fertilization-induced zinc spark is a novel biomarker of mammalian embryo quality and early development. Scientific Reports. 2016. 6:22772, doi:10.1038/srep22772 2.
2. Duncan FE*, Que EL*, Zhang N*, Feinberg EC, O’Halloran TV and Woodruff TK (2016). "The zinc spark is an inorganic signature of human egg activation." Scientific Reports.2016. 6: 24737. *Authors contribute equally.
3. Zhang N, Yoon SY, Parys JB, Fissore RA. Effect of M-phase kinase phosphorylations on type 1 inositol 1,4,5-trisphosphate receptor-mediated Ca responses in mouse eggs. Cell Calcium. 2015. PubMed PMID: 26259730 4. Zhang N, and Fissore RA (2014). "Role of caspase-3 cleaved IP3 R1 on Ca(2+) homeostasis and developmental competence of mouse oocytes and eggs." J Cell Physiol 229(11): 1842-1854.
5. Wakai T, Zhang N, Vangheluwe P, Fissore RA. 2013. Regulation of endoplasmic reticulum Ca(2+) oscillations in mammalian eggs. J Cell Sci 126(Pt 24):5714-5724.
6. Zhang N, Wakai T, Fissore RA. 2011. Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro-aged mouse eggs. Molecular Reproduction and Development 78(9):684-701. 7.Coward K, Ponting CP, Zhang N, Young C, Huang CJ, Chou CM, Kashir J, Fissore RA, Parrington J. 2011.
7.Identification and functional analysis of an ovarian form of the egg activation factor phospholipase C zeta (PLCzeta) in pufferfish. Molecular Reproduction and Development 78(1):48-56.
8.Wakai T, Vanderheyden V, Yoon SY, Cheon B, Zhang N, Parys JB, Fissore RA. 2011. Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation. J Cell Physiol, 227, 705-717.
9.Wakai T, Zhang N and Fissore RA. 2008. Caffeine prevents a loss of calcium oscillatory response associated with postovulatory aging of mouse oocytes. Reprod.Fertil.Dev. 21, 217-217.
Ongoing Research Grant Support
Woodruff (PI) 09/30/13 – 12/31/17
Non-Invasive Test of Egg Development Potential In this grant, we will test the hypothesis that the quantity of Zn2+ released at fertilization can be used to predict embryo quality.
Woodruff (PI) 04/01/13 – 03/31/18
Center for Reproductive Health After Disease The major goal of this application is to address the basic science need to understand human follicle and egg biology and pursue cutting-edge options for preserving reproductive health, while providing physicians, patients, their families, and the public with information about the risks posed by diseases and treatments to reproductive health that will lead to informed dialogue about options for preserving reproductive function. Role: Postdoctoral Researcher