Patrizia Casaccia

Patrizia Casaccia is an Italian neuroscientist who is the Director of the Neuroscience Initiative of the Advanced Science Research Center at the CUNY Graduate Center, as well as a Professor of Neuroscience, Genetics & Genomics, and Neurology at the Icahn School of Medicine at Mount Sinai. Casaccia is a pioneer in the study of myelin. Her research focuses on understanding the neurobiological and neuroimmune mechanisms of multiple sclerosis and to translate findings into treatments. Casaccia co-founded the Center for Glial Biology at Mount Sinai and CUNY and is one of the Directors of the center.

Early life and education Casaccia was born in the coastal city of Giulianova in the province of Teramo, Italy. She grew up with her mother, father, and younger brother in Giulianova Lido, in Matteotti street. She first explored the role of the PrPSC protein in scrapie pathogenesis and also innovated new methods of gene transfer in organotypic hippocampal brain slices to explore kainate receptor biology and electrophysiology. Her doctoral thesis explored sleep dysregulation in patients with brain illness. She went on to explore oligodendrocyte progenitor cell (OPC) development, discovering that the cyclin-dependent kinase inhibitor p27 is critical to OPC development, such that differentiation in impaired and proliferation continues. In addition to her research on oligodendrocytes, Casaccia studied neurotrophins and their role in cell survival and differentiation in the central nervous system.

Career and research Casaccia was recruited to Robert Wood Johnson Medical School in 1999. Casaccia started as an assistant professor, and was promoted to associate professor while running a lab that explored the neurobiological basis of demyelinating disorders.

In 2008, Casaccia was recruited to the Icahn School of Medicine at Mount Sinai in New York City. In 2016, Casaccia was appointed to Director of the Neuroscience Initiative within the Advanced Science Research Center at the CUNY Graduate Center. One major area of research in Casaccia's lab is probing the molecular and genetic mechanisms of oligodendrocyte development, myelin formation, and myelin loss. She found that p27 regulates the differentiation of oligodendrocytes by modulating transcription of the gene for myelin basic protein. The accumulation of proapoptotic molecules throughout development correlates with increased apoptosis, suggesting that manipulating the balance of these pro- and anti- apoptotic molecules could be useful as a strategy to prevent oligodendrocyte death. Casaccia found that male and female sex hormones have the capacity to regulate differentiation and maturation of oligodendrocytes. Casaccia and her colleagues later found a critical transcription factor, Yin Yang 1, in the differentiation of OPCs.

Therapeutic strategies targeting oligodendrocytes and myelin Casaccia shifted her focus more towards translation after becoming a professor at Icahn School of Medicine. Focusing on demyelinating diseases, Casaccia found that inhibition of p53 leads to decreased oligodendrogliopathy, myelin preservation, and decreased microglial infiltration, serving as a potential future therapeutic target.

Casaccia contributes to the development of a new model of multiple sclerosis pathogenesis that takes into account genetic risk susceptibility and cell-specific epigenetic changes that occur in the immune system and the nervous system. Casaccia and her team turned to a mouse model of social isolation and found that it had impaired myelination. Overall, they showed that enhancing or repairing myelination can act as a therapeutic strategy towards depressive-like social behaviors in mice. They found increased levels of ceramide in the CSF, and it led to oxidative stress and bioenergetic failure in the neurons of rats exposed to MS CSF.

Awards and honors 2001 New Jersey Cancer Commission Award for Scientific Excellence 2005 Rutgers Women in Neuroscience Award

Select publications S. Sauma, P. Casaccia. Gut-Brain Communication in Demyelinating Disorders. Current Opinion in Neurobiology, 2020, 62, 92–101. DOI: . K. Castro, P. Casaccia. Epigenetic modifications in brain and immune cells of multiple sclerosis patients. Mult Scler, 2018. DOI: 10.1177/1352458517737389. Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV. Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature. 383: pages 716–9. PMID 8878481 DOI: 10.1038/383716a0 Casaccia-Bonnefil P, Benedikz E, Shen H, Stelzer A, Edelstein D, Geschwind M, Brownlee M, Federoff HJ, Bergold PJ. Localized gene transfer into organotypic hippocampal slice cultures and acute hippocampal slices. Journal of Neuroscience Methods. 50: pages 341–51. PMID 8152244 DOI: 10.1016/0165-0270(93)90040-X Casaccia-Bonnefil P, Kascsak RJ, Fersko R, Callahan S, Carp RI. Brain regional distribution of prion protein PrP27-30 in mice stereotaxically microinjected with different strains of scrapie. 1993. The Journal of Infectious Diseases. 167: pages 7–12. PMID 8093365