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Jean-Ju Chung, PhD, MS

Associate Professor of Cellular & Molecular Physiology
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About

Titles

Associate Professor of Cellular & Molecular Physiology

Biography

Jean-Ju L. Chung received her bachelors and masters degree from Seoul National University, Korea and her Ph.D. from Johns Hopkins University in 2007. She was a postdoctoral fellow with David E. Clapham in the Department of Neurobiology at Harvard Medical School. She joined Yale's Department of Cellular and Molecular Physiology as a faculty member in September, 2015.

Her research is devoted to investigating cellular signaling via the membrane receptors and ion channels, with a current emphasis on mature spermatozoan motility and fertilization capacity. She has focused her efforts on the primary calcium channel of spermatozoa, CatSper, and has defined its molecular and spatial organization in spermatozoa and its function in fertility regulation. The Chung laboratory applies novel technologies to sperm biology and reproductive research to study physiologically relevant molecular changes during mammalian fertilization for reproductive medicine.

Appointments

Education & Training

Instructor
Harvard Medical School, Children's Hospital Boston (2015)
Postdoctoral fellow
Harvard Medical School, Children's Hospital Boston (2012)
PhD
Johns Hopkins University School of Medicine, Neuroscience and Biochemistry (2007)
MS
Seoul National University, Neuroendocrinology (1999)
BS
Seoul National University, Molecular Biology (1997)

Research

Overview

In humans, only about 200 out of 200 million spermatozoa ever reach the oviduct and of these only one spermatozoon fertilizes the egg. During the life-changing journey, sperm cells not only adapt to changes in local environments, but also respond to cues along the female reproductive tract. Ion channels and transporters enable sperm to respond to the constantly changing environment by controlling the sperm’s calcium and proton concentrations that in turn results in changes in motility. However, the molecular details are largely unknown.

A current focus of our research is to understand the mechanisms by which the sperm motility and male fertility are regulated by ion channels. In particular, we are studying the sperm-specific calcium channels “CatSpers that are essential for sperm hyperactivation (an asymmetric flagellar motion of the sperm tail that gives spermatozoa the force to penetrate the zona pellucida of the egg.)

First, we characterized the native CatSper channel complex, identifying novel CatSper accessory subunits to better understand molecular organization of the CatSper channel and its signal transduction in mammalian fertilization. The accessory subunits are key to understand the assembly and the organization of an ion channel complex. By generating mice lacking each subunit we found that one of their function is to protect the pore-forming subunits from premature degradation, and that only the properly assembled, complete channel complex can be specifically targeted to the flagellar membrane.

Calcium signaling specificity is accomplished via the ion’s precise spatiotemporal localization in a cell. Mammalian sperm has elaborate cytoskeletal structures in the tail for motility regulation. As the sperm flagella is less than 1 um in diameter, the spatial information of the signaling molecules inside the flagella cannot be resolved by conventional light microscope due to diffraction limit of light. Thus, we have applied super-resolution stochastic optical reconstruction microscopy (STORM) to image CatSper and the potential downstream signaling molecules within the flagella. Our studies showed that the CatSper channel forms unique four linear calcium domains that organize calcium signaling proteins along the flagella, providing strong evidence for molecularly defined, structured calcium signaling domains. These domains orchestrate the timing and extent of complex phosphorylation cascade, potentially coordinating the flagellar waveform. We are currently studying the molecular mechanisms by which CatSper and calcium signaling molecules are organized in the four distinct lines.

Most importantly, we demonstrated that capacitation (a physiological process that enables spermatozoa to obtain the fertilizing ability in the female reproductive system through biochemical and functional changes) results in heterogeneous sperm populations with molecular differences in the CatSper spatial domains. These data suggest that the exceptionally few spermatozoa that reach the egg have a distinct molecular signature from those that fail in the female reproductive tract! Ongoing projects address characterization of the successful spermatozoa at the molecular levels. We are particularly interested in the molecular changes of the sperm membrane receptors and ion channels during navigation in the female reproductive tracts in situ.

Disruption of many of membrane receptors and ion channels leads to infertility in humans. The information gained from our research will improve in vitro fertilization methods and enable new contraceptive approaches. Ultimately, our research shall explain they very first life event that allows all the subsequent animal physiology.

Medical Subject Headings (MeSH)

Fertility; Ion Channels; Membrane Microdomains; Reproduction; Signal Transduction; Sperm Capacitation; Sperm Motility

Research at a Glance

Yale Co-Authors

Frequent collaborators of Jean-Ju Chung's published research.

Publications

2023

2022

Academic Achievements & Community Involvement

  • honor

    Highly Cited Researcher 2020 (top 1% citation in field and year 2020)

  • honor

    Janice Bahr Junior Scientist Travel Award

  • honor

    Highly Cited Researcher 2019 (top 1% citation in field during 2008-2018)

  • honor

    FASEB SRC on Ion Channel Regulation Travel Award

  • honor

    Rudolf J Anderson Fellowship

Get In Touch

Contacts

Academic Office Number
Office Fax Number
Mailing Address

Cellular & Molecular Physiology

Yale School of Medicine, SHM-B147, 333 Cedar street

New Haven, CT 06510

United States

Locations

  • E36C

    Academic Office

    Sterling Hall of Medicine, B-Wing

    333 Cedar Street

    New Haven, CT 06510

  • E07

    Lab

    Sterling Hall of Medicine, B-Wing

    333 Cedar Street

    New Haven, CT 06510