Megan Agajanian, in the lab of Ben Major, PhD, and Juanita Limas, in the lab of Jean Cook, PhD, will receive up to $150,000 each to support their biomedical research at the UNC School of Medicine and the UNC Lineberger Comprehensive Cancer Center.
UNC School of Medicine graduate students Megan Agajanian and Juanita Limas were named 2018-19 Gilliam Fellows by the Howard Hughes Medical Institute (HHMI) this summer. Each will receive $50,000 for each of the next three years to support their basic science research conducted in the labs of Ben Major, PhD, associate professor of cell biology and physiology, and Jean Cook, PhD, professor of biochemistry and biophysics and associate dean for graduate education. Both Major and Cook have joint appointments in pharmacology and are members of the UNC Lineberger Comprehensive Cancer Center.
In 2016, Tigist Tamir, also in the Major lab, was the first UNC School of Medicine graduate student to receive the prestigious HHMI Gilliam Fellowship.
Agajanian studies the cascade of proteins that make up the WNT signaling pathway, which is critical for embryonic development and is commonly misregulated across diseases, including numerous cancer types, bone density disease and several neurodegenerative diseases. Therapies targeting WNT have yet to show clinic benefit. Therefore, identifying new drug targets in this important protein pathway could have a significant impact on improving patient outcomes.
The overarching goal of Agajanian’s graduate work is to identify new regulators of the WNT signaling cascade and to figure out how they control pathway activity. Her current work focuses on the protein AAK1, a kinase the Major lab identified as an inhibitor of WNT signaling; it is misregulated in neurodegenerative diseases. Agajanian and her Major lab colleagues have shown that AAK1 downregulates WNT signaling by promoting the internalization and degradation of the WNT receptor – when the proteins that bind to the receptor are subsumed into the cell.
“We, in collaboration with the Structural Genomics Consortium at UNC, have developed and validated an AAK1 specific inhibitor that, with further testing, could prove useful in the clinic,” Agajanian said.
In the Cook lab, Limas studies the crucial moments immediately prior to DNA replication. To maintain proper health, cells must copy their DNA precisely every time they divide. But before copying, DNA must be preloaded with key essential proteins. If this preparation process is uncoordinated, the consequences could be cell death or the development of cancer cells.
There is evidence that cancer cells are continually mutating their DNA, but scientists don’t fully understand the process leading to these mutations. Limas will lead the effort in Cook’s lab to test the idea that the genes frequently changed in cancers can cause problems in the preparation steps for copying DNA.
“We will systematically insert cancer-causing genes (oncogenes) into normal cells, and then test if these cells prepare for copying their DNA differently,” Limas said. “For this project, we developed a state-of-the-art method that analyzes the DNA preparation in individual cells.”
Using this method, Limas will assign individual oncogenes to specific outcomes for precise DNA copying – an assignment that has been difficult thus far throughout the scientific community.
“At the end of this project, we will match individual cancer genes to the kinds of changes they cause,” Limas said. “And we think this information will aid in the diagnosis of specific kinds of cancer and the selection of individual therapies for patients.”
The HHMI Gilliam Fellowships for Advanced Study program promotes excellence in the life sciences and related fields by supporting PhD students committed to a career in academic research, and faculty and training programs dedicated to developing the talents of promising graduate students from underrepresented groups. The main goal of program is to ensure that a diverse and highly trained workforce is prepared to assume leadership roles in science, particularly college and university faculty who have the responsibility to develop the next generation of scientists.
The fellows’ mentors are expected to participate in workshops designed to improve their mentoring skills and sharpen their ability to evaluate themselves as mentors to a diverse and inclusive pool of future scholars.
“Selection as an HHMI Gilliam Fellow is an honor and an opportunity to participate in the development of future scientific trailblazers,” Cook said. “These student awardees have tremendous potential for future research leadership. And the UNC School of Medicine is also proud that HHMI recognizes the long-standing institutional investment in research training.”
The nomination process, review criteria, and faculty training are intended to encourage participating institutions to adopt activities and policies that promote inclusion and the development of talented scientists from all backgrounds.
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