Honors and Awards

Researchers Downes, Pak Win 2021 Armstrong Fund for Science Award at UMass Amherst

The Armstrong Fund for Science at UMass Amherst has announced that its 2021 award will go to Gerald Downes, biology, and ChangHui Pak, biochemistry and molecular biology, for their collaborative project that seeks to better understand how mutation of a gene known as TBCK disrupts brain development. Mutations in the TBCK gene cause a rare, severe, poorly understood neurological disease called TBCK Syndrome. Downes and Pak will receive a two-year, $40,000 grant to support preliminary investigations in preparation for a full-blown research effort.

NEWS Gerald Downes
Gerald Downes
NEWS ChangHui Pak
ChangHui Pak

Benefactors John and Elizabeth Armstrong established their Fund for Science in 2006 to identify and support promising research directions that do not yet have enough data available for the principals to apply to standard funding channels.

Michael Malone, vice chancellor for research and engagement, administers the Armstrong award process. He said, “I am very excited to see this collaborative project receive this critical early support thanks to the generous commitment of the Armstrongs.”

Mutations in the TBCK gene were only identified as causing TBCK Syndrome in 2016, a devastating affliction that results in progressive loss of muscle tone, intellectual disability, drug-resistant epilepsy, and a high rate of childhood and adolescent mortality. It’s not yet known how mutations in this gene cause disease, but cells from TBCK Syndrome patients show reduced mechanistic Target of Rapamycin, or mTOR, signaling. mTOR is at the center of a biochemical pathway that connects interior processes of a cell with its exterior environment. One example of this is that cells can respond to the relative availability of exterior nutrients by growing. Most of the time, mTOR signaling works flawlessly, but when it doesn’t, serious complications can result.

“We don’t really understand what’s going on here,” says Downes. “And there are no real treatments for TBCK Syndrome available. Right now, you can only treat the symptoms, but our goal is to be able to eventually create therapeutics that can cure the disease.” Though TCBK Syndrome is rare, it might provide insight into how mTOR signaling is regulated. Since many other diseases are caused by abnormal mTOR signaling, any light that Downes and Pak can shed on the TBCK Syndrome could have wide-ranging ramifications.

Downes and Pak plan a two-pronged approach: Downes, who has worked for years with zebrafish, has already engineered a variety of the fish with TBCK Syndrome. His lab will study how TBCK effects brain development and interacts with the mTOR pathway. Pak is an expert in the use of human-induced pluripotent stem cells. “We can grow these stem cells, reprogram and rewind them back to the embryonic stage of brain development,” she says. “Then we can engineer specific mutations, like TCBK, grow the stem cells into neurons, and run a variety of studies to compare and contrast the healthy cells with the abnormal ones.”

“We’ll be working in parallel,” says Downes, “learning from the insights provided by each model.”

Once they have preliminary results in hand, Downes and Pak will be well-positioned to seek major, multi-year support for a more comprehensive study. “The Armstrong Fund is letting us jump-start our project,” says Pak. “Without this support, it would be difficult to get our work off the ground.”