Cambi Laboratory

My research program has focused on deciphering basic mechanisms of myelin development and disease using cell cultures and mouse models and linking these findings to human disease. Oligodendrocytes and myelin play a critical role in maintaining integrity of axons and neurons through glia-axon signaling. Disruption of their function is implicated in many neurological disorders that affect both white and grey matter, such as inherited myelin disorders, Multiple Sclerosis, Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS).

The overarching goal of the current research is to elucidate the molecular mechanisms that underlie oligodendrocyte and myelin mediated support of neuronal cell and neural circuitry integrity in models of neurodegeneration. Our current projects are: 1. To understand the protective role of oligodendrocytes and myelin in neuronal cell health and neural network integrity following implantation of neural interfaces and develop strategies to enhance their support and improve recording longevity. This project is in collaboration with Dr. Kozai in Bioengineering. 2. To investigate how oligodendrocyte and myelin loss contribute to selective neuronal vulnerability in Alzheimer Disease. To investigate the neuroprotective function of myelin and oligodendrocytes we have generated a novel hypermyelinating App mouse model and are characterizing clinical, pathological and molecular markers of disease progression. 3. To identify molecular signatures and genes in glial and neuronal cells that are associated with neuroprotection as potential targets for future therapeutic interventions we are using single cell transcriptomics and spatial transcriptomics.

1. Xing B, Brink LE, Maers K, Sullivan ML, Bodnar RJ, Stolz DB, Cambi F. Conditional depletion of GSK3b protects oligodendrocytes from apoptosis and lessens demyelination in the acute cuprizone model. Glia. 2018 Sep;66(9):1999-2012. doi: 10.1002/glia.23453. Epub 2018 May 15.PMID: 29761559

2. Espay AJ, Vizcarra JA, Marsili L, Lang AE, Simon DK, Merola A, Josephs KA, Fasano A, Morgante F, Savica R, Greenamyre JT, Cambi F, Yamasaki TR, Tanner CM, Gan-Or Z, Litvan I, Mata IF, Zabetian CP, Brundin P, Fernandez HH, Standaert DG, Kauffman MA, Schwarzschild MA, Sardi SP, Sherer T, Perry G, Leverenz JB. Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases. Neurology. 2019 Feb 12;92(7):329-337. doi: 10.1212/WNL.0000000000006926. PMID:30745444

3. Guzman K, Brink LE, Rodriguez-Bey G, Bodnar R, Kang L, Xing B, Sullivan M, Park HJ, Koppes E, Zhu H, Padiath Q, Cambi F. "Conditional depletion of FUS in oligodendrocytes leads to motor hyperactivity and increased myelin deposition associated with Akt and cholesterol activation", GLIA 2020, DOI: 10.1002/glia.23825

4. Wellman SM, Guzman K, Stieger K, Brink LE, Sridhar S, Dubaniewicz MT, Li L, Cambi F, Kozai TDY. “Cuprizone-induced oligodendrocyte loss and demyelination impairs recording performance of chronically implanted neural interfaces” Biomaterials 2020 May;239:119842. doi: 10.1016/j.biomaterials.2020.119842. Epub 2020 Feb 6.

5. Keying Chen, Franca Cambi, Takashi Kozai. “Pro-myelinating Clemastine administration improves recording performances and neuronal health of the chronic microelectrode implantation”. Biomaterials 2023 Jun 21. 10.1016/j.biomaterials.2023.122210.

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/franca.cambi.1/bibliography/public/