Page 36 - RU Robert Wood Johnson Medicine • Summer 2020
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Asany researcher knows, it’s serendipity that often opens the door to major scientific discovery. For M. Chiara Manzini,
PhD, recently named associate professor of neuroscience and cell biology at Rutgers Robert Wood Johnson Medical School and resident scientist at the Child Health Institute of New Jersey, the unexpected break came as part of her discovery of mutations in the CC2D1A gene in individuals affected by autism spectrum disorder, intellectual disabilities, and seizures.
“We constantly try to identify new genes, and mutations to those genes, that can help explain to families and other scientists the causes
of neurodevelopmental disorders,” says M. Chiara Manzini, PhD. “The next step will be using that information to explore novel drug treatments—and that’s an area we’re quite
excited about.”
As a postdoctoral fellow at Boston Children’s Hospital/Harvard Medical School, Dr. Manzini had both identified CC2D1A mutations in patients and removed the gene in a mouse model to understand how its loss would affect brain development and be- havior. What she may have unlocked instead is a molecular pathway that helps explain the sex bias in diagnosis of autism—boys are diagnosed with the disorder at a 4-to- 1 rate compared to girls—as well as in other neurological and psychiatric disorders. Supported by a grant from the National Institutes of Health, her new lab in the Child Health Institute is in dogged pursuit of that biological trail.
They discovered a striking difference between male and female mouse models when CC2D1A was removed. Dr. Manzini recalls, “While the males had cognitive and social deficits, hyperactivity, and anxiety, the females only had mild learning issues. What we found was that there are dif- ferences in how this gene functions in the male brain versus the female brain, and that triggered a whole new line of research into sex bias in autism.” The end game, she adds, is to understand the molecular mechanisms behind gender differences in
diagnosis, and in doing so, uncover a druggable pathway that could ultimately alter the imbalance in humans.
Dr. Manzini’s new lab is working to achieve that goal. The Child Health Institute is embedded in a cluster of academic and clinical facilities on the medical school campus that includes the Department of Pediatrics and the Pediatric Clinical Research Center, the Bristol-Myers Squibb Children’s Hospital at Robert Wood Johnson University Hospital, and the PSE&G Children’s Specialized Hospital. Having left smaller quarters at George Washington University in the summer of 2019, she calls Rutgers “the perfect home” to conduct her complex research, which involves identifying genes that are critical to human brain function and defining the molecular triggers of neurodevelopmental disorders, such as autism, brain malformations, and intellectual
disabilities.
“Being here will give me the ability to go back and forth between mouse and zebrafish models and humans to establish
these molecular differences in neurons,” explains Dr. Manzini, who was born in a small town near Bologna, Italy, and initially trained in human genetics at the University of Pavia, the country’s leading genetics institute.
Another catalyst for Dr. Manzini’s move to New Brunswick was the ability to be part of a thriving academic community that includes experts in not just the neurosciences but also immunology, pediatrics, and reproductive sciences. This collab- oration becomes ever more important given her lab’s new focus on the influence of sex hormones on brain development and her plans to expand that research into therapeutic areas that could include stem cells, gene therapy, and small molecules with drug potential. The fact that Rutgers houses one of the nation’s largest repositories of human stem cell samples that can be differentiated into neurons was also part of the irresistible attraction for Dr. Manzini.
From the countless hours spent in the lab—alongside her growing team of fellows and undergraduate students she relishes training—there is no greater reward for Dr. Manzini than being able to provide answers to families whose lives have been reshaped by genetic disease. “We constantly try to identify new genes, and mutations to those genes, that can help explain to families and other scientists the causes of neurodevelopmental disorders,” she says. “The next step will be using that information to explore novel drug treatments—and that’s an area we’re quite excited about.” M
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