M. Chiara Manzini, PhD

Dr. M. Chiara Manzini is an Associate Professor in the Department of Neuroscience and Cell Biology at Rutgers Robert Wood Johnson Medical School. She was initially trained in Human Genetics at the University of Pavia in Italy and received her PhD in Neurobiology and Behavior at Columbia University exploring how neuronal circuits are assembled during development in both normal and diseased brains. With this combined expertise, Dr. Manzini then joined Dr. Chris Walsh’ group at Boston Children’s Hospital/Harvard Medical School to further train in Neurogenetics. She started her independent career as an Assistant Professor in the Institute for Neuroscience at the George Washington University. The main goal of Dr. Manzini’s research is to bridge the genetics and mechanisms of disease to identify genes that are essential for human cognition and to define the molecular mechanisms underlying neuromuscular and neurodevelopmental disorders.

The Manzini lab studies the cellular and molecular mechanisms of cognitive development and of neurodevelopmental diseases. Our work combines human genetics with molecular, cellular, and behavioral approaches in murine and zebrafish models to link human genetics to neuronal cell biology and behavior. Current focuses of the lab are signaling pathways establishing sex bias in autism and other neurodevelopmental conditions and the role of extracellular matrix in neuromuscular disease.

The main goal of Dr. Manzini’s research is to bridge the genetics and mechanisms of disease to identify genes that are essential for human cognition and to define the molecular mechanisms underlying neurodevelopmental disorders focusing on autism and neuromuscular disorders. During the past decade her research has:

• Identified multiple genetic causes of cognitive deficits and neuromuscular disorders to provide a genetic diagnosis to patients
• Developed novel animal models in both mouse and zebrafish exploring the mechanisms of disease focusing on how signals are transmitted from cell to cell through protein modifications such as phosphorylation and glycosylation
• Found male-specific signaling changes in a mouse model of intellectual disability (ID) and autism spectrum disorder (ASD) that could be involved in the male bias in diagnosis of these disorders.

The Manzini lab combines human genetics with molecular, cellular, and behavioral approaches in murine and zebrafish models to link human genetics to neuronal cell biology, intracellular signaling, and behavior. Our recent work builds on our previous findings to develop pre-clinical animal models to test novel therapies for cognitive and social deficits.  In particular, we are leveraging our previous findings of sex-specific signaling controlled by the ASD/ID gene CC2D1A to identify the molecular mechanisms that underlie sex bias in diagnosis of ASD and ID. In parallel, we are developing novel zebrafish models of congenital muscular dystrophies with eye and brain malformations to perform high-throughput drug screens. Finally, we continue our gene hunting efforts in neuromuscular and neurodevelopmental disorders with particular focus on mutations outside of the coding regions of genes that could escape standard analysis methods.

• Saredi S, Cauley E.S., Spivey T., Ardissone A., Ruggieri R., Mora M., Moroni I., Manzini M.C. Myopathy associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK Muscle and Nerve 62(2):266-271 (2020)

• CauleyE.S., PittmanA., MummidivarpuS., KarimianiE.G., MartinezS., Moroni I., Podini D., Mora M., Jamshidi Y., Hoffman E.P., Manzini M.C. Novel mutation identification and copy-number variant detection via exome sequencing in congenital muscular dystrophy Mol Genet Genom Med 8(11):e1387 (2020)

• Mossa A, Manzini M.C. Molecular causes of sex-specific deficits in animal models of neurodevelopmental disorders J Neurosci Res 99(1):37-56 (2021) (Peer-reviewed invited review) (Top downloaded article)

• Pond H.L., Heller A.T., Gural B.M., McKissick O.P., Wilkinson M.K., Manzini M.C. Digging Behavior Discrimination Test to probe burrowing and exploratory digging in male and female mice J Neurosci Res 99(9):2046-2058 (2021)

• Bhattacharya A., Manzini M.C. Unraveling the mysteries of MYT1L: From reprogramming factor to multifaceted regulator of neuronal differentiation Neuron 109(23):3713-3715 (2021) (Invited Preview)

• Osborn D., PondH.L., MazaheriN., DejardinJ., MunnC.J., Mushref  K., CauleyE.S., MoroniI., PasanisiM.B., SellarsE.A., HillR.S., PartlowJ.N., WillaertR.K., BharjJ., MalamiriR.A.,GalehdariH., ShariatiG., MaroofianR., MoraM., SwanL.E., VoitT., ContiF.J., Jamshidi Y., Manzini M.C.Mutations in INPP5K cause a form of congenital muscular dystrophy syndrome overlapping Marinesco-Sjögren Syndrome and the dystroglycanopathies Am J Hum Genet 100(3):537-545 (2017)

• Zamarbide M., Mossa A., Muñoz Llancao P.A., Wilkinson M.K., Pond H.L., Oaks A.W., Manzini M.C. Male-specific cAMP signaling in the hippocampus controls spatial memory deficits in a mouse model of autism and intellectual disability Biol Psych 85(9):760-768 (2019)

• Saredi S, Cauley E.S., Spivey T., Ardissone A., Ruggieri R., Mora M., Moroni I., Manzini M.C. Myopathy associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK Muscle and Nerve 62(2):266-271 (2020)

• Mossa A, Manzini M.C. Molecular causes of sex-specific deficits in animal models of neurodevelopmental disorders J Neurosci Res 99(1):37-56 (2021) (Peer-reviewed invited review) (Top downloaded article)

• Pond H.L., Heller A.T., Gural B.M., McKissick O.P., Wilkinson M.K., Manzini M.C. Digging Behavior Discrimination Test to probe burrowing and exploratory digging in male and female mice J Neurosci Res 99(9):2046-2058 (2021)