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Home » Discover Rackham » Student Spotlight: I-Uen (Yvonne) Hsu

In 1996, scientists mapped out the STAC (SH3 and cysteine rich domain) family of genes. Since then, their function has been somewhat of a mystery. That is, until around twenty years later when in Dr. John Kuwada’s lab at University of Michigan, a group of researchers including Ph.D. candidate I-Uen (Yvonne) Hsu discovered the STAC3 gene’s purpose and the mechanism underlying it.

We know that every living thing is made of cells, and those cells form different systems, all serving varying functions. There are two different types of cells that can change the voltages of their membranes in order to pass electricity—muscles and neurons. Neurons are able to fire (change voltage) because the proteins that make up channels on the cell membranes provide a space through which ions can pass. Genes, like those in the STAC gene family, regulate those channels, depending on their specific function.

There are stac1, stac2, and stac3 in the stac gene family that is conserved across species. The Kuwada lab identified the stac3 gene in zebrafish by a mutagenesis screen and found that it is specifically expressed in skeletal muscles and required for contraction. Upon mutating the zebrafish by eliminating the stac3 gene, it was unable to move. Yvonne’s first project in the Kuwada lab was to figure out just how the stac3 gene regulates skeletal muscle contraction. Significantly, they found that stac3 modulates key properties of a voltage-gated calcium channel that makes the contraction possible.

Most intriguing to Yvonne and Dr. John Kuwada is that other members of the stac gene family (stac1 and stac2) are specifically expressed in the central nervous system, but their function is poorly understood. Yvonne and her fellow researchers have begun to apply their findings about stac3 in zebrafish skeletal muscles to fruit flies, as they seek to find the function of the neural stac genes. “The fruit fly has an expansive genetic toolbox for manipulation and is a simpler model organism to answer questions in neuroscience,” she explains.

Recently, Yvonne published a paper demonstrating that in fruit flies, the stac gene is required for normal circadian rhythm. This paper is the first to show the neuronal function of the neural stac gene. If possible, Yvonne hopes her analysis of the stac gene in fruit flies can be applied when examining the neural stac genes role in the central nervous system of vertebrates.

Most notably, previous members in the Kuwada lab mapped out that a missense mutation in the human STAC3 gene is the nature of a debilitating congenital muscle disease, resulting in severely reduced muscle strength. Similarly, by understanding the role of the stac genes in the central nervous system, we may be able to find causes and potential treatments for some neurological disorders.

“Neuroscience is still a mystery, so every step and discovery is going to be significant. The causes of many neurological diseases are unknown—we know the outcome, but we don’t know how and why. If we did, we could find treatments that are more effective. Sometimes, we have to go back to basic science,” Yvonne explains.

From Taiwan to Ann Arbor

Yvonne, originally from Taiwan, knew she wanted to pursue a graduate degree, and she knew she wanted to do so in the United States. After learning more about the Molecular, Cellular, and Developmental Biology program at Michigan and connecting with faculty members, she knew U-M would be the place where she could get the collaboration and support she needed for her research to flourish.

“I could tell the people were creative and allowed freedom for flexibility in their research. It’s really motivating to be in an environment like we have at Michigan. Specifically, my advisor provides me opportunities to pursue fundamental neuroscience questions by employing a strategy that examines several different organisms with a combination of molecular, cellular, genetic and behavioral tools, and I really appreciate it.”

As a graduate student, Yvonne spends many of her waking hours in the lab, but has made connections with equally diligent peers. “I came from Taiwan alone, so it’s been an adventure and a culturally stimulating experience. I’ve met people from so many different places, and we talk about everything from science to future plans.”

Upon completion of her Ph.D., Yvonne hopes to continue in academia as a faculty member. “I’ll look for an opportunity as a postdoc, and hopefully that will help me determine what I want to do in my own lab one day.”

The Importance of Funding

Yvonne has received funding in multiple forms, including the Chia-Lun Lo Fellowship; the Barbour Scholarship, one of Rackham’s most prestigious funds; and most recently, the Rackham Predoctoral Fellowship.

“Science can be an isolating environment—you spend time in the lab, you produce data, you write the manuscripts, and you wonder if anyone appreciates it. Funding is so reassuring and it motivates graduate students to continue working hard. It allows us to use our time to make the cutting-edge discoveries that move our fields forward.”

Rackham Graduate School will be closed for the Thanksgiving holiday at 5:00 p.m. on Wednesday, November 21. We will return at 8:00 a.m. on Monday, November 26. During the holiday, there will be no processing of application materials and no updates to your Wolverine Access account. After we reopen, there will be a delay in processing application materials. Thank you for your patience as we process the high volume of materials.