By: Ada Chong
June 2023
Three decades ago, Timothy Gershon delved into developmental neuroscience research and wanted to explore a clinical direction that could be relevant to his research expertise. He decided to specialize in child neurology, specifically taking care of kids with brain tumors. Dr. Gershon realized that his interest in cell division in the nervous system was clinically relevant and could lead to translational research in brain tumor biology.
Dr. Gershon’s interest in neurology grew from his fascination with the nervous system. He says, “I love the way the nervous system is so responsive to the external environment. We see something and we picture it in our mind, the neurons are constantly interacting. Even though there’s fast changes, there’s also slow changes as people learn and grow up. Even during early brain growth, there’s changes that are long-term, the immediate interaction to the environment with these slow long-term changes got me interested in the nervous system. Neurology is the area of medicine that interacts with the nervous system most directly.”
The research Dr. Gershon is currently studying looks at how the brain grows to the correct size. In this context, brain tumors result from an area in the brain growing more than it should. In brain tumors, cells in the brain mistakenly think they’re supposed to be doing what they’re doing, they grow and try to survive, but it’s not an adaptive program and is based on normal growth programs during brain development that get triggered inappropriately after a person is born and grows a huge brain beyond the point where new tissue growth is needed. The cells mistakenly think it should be growing new tissue. There are rules cells are trying to enact, and they’re not just growing randomly.
Dr. Gershon’s research on the brain tumor side aims to understand what the rules and instructions brain tumors are following and how he can use that knowledge to devise new and more targeted treatments. This pre-clinical work aims at understanding fundamental principles to design drugs and clinical trials. Dr. Gershon and his team work through these basic questions through translational questions. They have therapies they are trying to work through clinical trials. CT-179 is a drug that targets stem cells in brain tumors. These cells are relatively resistant to regular standard therapies. When children with medulloblastoma are always treated with surgery, radiation and chemotherapy, and 80% of the kids are cured. This means that 20% of the tumors recur and recurrence is not curable. Dr. Gershon and his team are working to find a way to treat the 20% with incurable tumors. They think what happens in treatment failure is that the tumor stem cells that are not killed by radiation in chemotherapy, called “persister cells” repopulate the tumor. To address these persister cells that drive recurrence, they are trying to identify drugs that can rewire tumor stem cells, so they will not repopulate the tumor and regrow. They are working with CT-179, a new drug that targets a gene called OLIG2, that switches on in stem cells.Dr. Gershon believes disrupting OLIG2 with CT-179 will prevent the stem cell from regrowing the tumors. In his lab, Dr. Gershon found giving CT-179 and pairing it with radiation therapy, will improve lifespans and prevent recurrent brain tumors.
Another aspect of research Dr. Gershon studies is microcephaly, which happens when the brain does not grow enough. Many of the same genes that are dysregulated in brain tumors that cause overgrowth are also functioning incorrectly in microcephaly. Dr. Gershon focuses on conditions on brain undergrowth in his lab. He says these two things go hand in hand and the more they can understand neurodevelopment science, the better they can treat microcephaly and brain tumors.
Dr. Gershon came to Emory to take on the role of Director of Children's Center for Neurosciences Research (CCNR). His goal for this role is to link developmental neuroscience with medical practice and to have translational application in the science he’s interested in. He hopes to connect with other faculty doing neuroscience to build ties with neurology and promote translational science more broadly. Dr. Gershon also hopes to grow his brain tumor investigations by working with faculty studying neuro-immunology. Currently, he is learning how tumors communicate with immune cells to promote tumor growth and hopes to develop drugs to block these communications, as a new tumor treatment.