UVA School of Medicine

Fall 2022 3 to work specifically on the intersection of malnutrition and tuberculosis. Similar collaborative models through UVA's Division of Infectious Diseases and Center for Global Health Equity have already trained 177 international students of varying academic stages over the last decade. Of those, almost 90% remain in research careers. "Prioritizing the education of international trainees in global health benefits us all," says Heysell. "We can do more to follow the lead of young scientists in settings bearing disproportionate poverty." One of the strengths of the program is its diversity. Eleven of the faculty members are from UVA, and seven are Tanzanian. Eight are women. That allows the program to connect the postdocs with Tanzanian mentors and with secondary mentors from UVA, providing the trainees access to a broad breadth of experience and expertise. The program will be led by Heysell and Stellah Mpagama, MD, PhD, director of research and innovation at Tanzania's Kibong'oto Infectious Diseases Hospital, adjunct faculty at UVA, and the recipient of the Dr. Maria Kamm Best Female Scientist in Tanzania for 2022. "This program will enable Tanzanians to develop research leaders that will take forward the agenda of 'End TB' in the country," says Mpagama. "In the past decade, the collaborative research we conducted enlightened us a lot on the various challenges that impede TB control. The next steps are to develop solutions simultaneously with the development of research leaders to ensure continuity of the scientific efforts to curb this long-standing epidemic." The researchers are excited about the potential of the training partnership to not only help prevent and treat tuberculosis in Tanzania but to generate new discoveries that will help battle diseases of poverty around the world. "As ancient human conditions, malnutrition and tuberculosis do not often grab headlines," Heysell says. "Yet our collective progress in improving these conditions is a bellwether in how well we are doing to reduce other socioeconomic inequities." Gene That Causes Deadliest Brain Tumor Also Causes Childhood Cancer A gene that UVA Health researchers discovered is responsible for the deadliest type of brain tumor is also responsible for two forms of childhood cancer, the scientists have found. The new discovery may open the door to the first targeted treatments for two types of rhabdomyosarcoma, a cancer of the soft tissue that primarily strikes young children. Research suggests that the gene may also play an important role in other cancers that form in muscle, fat, nerves, and other connective tissues in both children and adults. "We accumulated multiple lines of evidence supporting the gene AVIL is a powerful driver for both major types of rhabdomyosarcoma," says researcher Hui Li, PhD, of the University of Virginia School of Medicine's Department of Pathology and UVA Cancer Center. "The tumors are oncogene addicted to AVIL, which supports the rationale to design therapeutic interventions to target AVIL in this childhood cancer." Rhabdomyosarcoma Gene Li and his team discovered in 2020 that the gene AVIL is the oncogene responsible for glioblastoma, the most lethal form of brain cancer. Less than 7% of patients with glioblastoma survive five years after diagnosis. Li's 2020 discovery was named one of the year's biggest biomedical discoveries by the editors of health news site STAT. Li's latest work builds on that research and suggests that AVIL is even more important than previously realized. Malfunctions in AVIL, Li and his team found, play an essential role in the development of the two main subtypes of rhabdomyosarcoma. In a scientific paper outlining the findings, he and his colleagues describe rhabdomyosarcoma as "addicted" to the gene's excess activity. They ultimately label AVIL a "bona fide oncogene" for rhabdomyosarcoma. AVIL may be the convergence point for two different cellular processes that cause soft-tissue cells to become cancerous, the researchers note. The scientists found that blocking the activity of AVIL prevented the formation of rhabdomyosarcoma in both cell samples in lab dishes and in mouse models of the disease. That's a promising sign for the discovery's potential to lead to a new, targeted treatment for rhabdomyosarcoma, a cancer that is relatively rare but can be deadly. Even with multi- modal therapeutic interventions, the survival rate for high-risk children is less than 20%. The new research also reveals that AVIL is excessively active in other cancers of the soft tissue, known as sarcomas. The scientists found that the degree of excess activity correlates with patient outcomes, suggesting that AVIL may be a vulnerability for those cancers as well. "These findings, plus our previous work in brain tumor, suggest that AVIL is an oncogene that, when over-activated, may trigger the development of multiple cancer types," Li says. Hui Li, PhD

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