Nicole Scott-Hewitt, Ph.D. (University of Rochester)
Assistant Professor of Cell Biology
Email: Nicole.scott-hewitt@duke.edu
Address:
Nanaline Duke Building room 318
307 Research Drive
Durham, NC 27710
Telephone: 919.613.9154
Overview
The Scott-Hewitt lab is investigating how interactions between cells and molecules derived from the nervous and immune systems influence critical molecular, cellular, and organismal functions. Our work aims to dissect glial and neuroimmune mechanisms that underlie vulnerability in aging and disease, and to provide mechanistic insights into how intercellular interactions and immunological changes impact cognitive function and contribute to neuropathology.
As a postdoctoral fellow in the laboratory of Dr. Beth Stevens at Boston Children’s Hospital, I investigated how neuroimmune interactions shape the brain across development and aging and discovered a unique role of a neural-extrinsic immune protein in critical intraneuronal processes. We found that the microglial-secreted complement protein C1q undergoes RNA-dependent liquid-liquid phase separation (LLPS) and interacts with neuronal ribonucleoprotein (RNP) complexes in an age- and RNA-dependent manner, altering neuronal protein homeostasis in vivo in the adult brain (Scott-Hewitt et al, PMID 38942014). This work highlights spatiotemporal specificity of neuroimmune activities, demonstrating how shifting molecular interactions may contribute to unique, cell-specific functions across time and under pathological conditions.
As an Assistant Professor at Duke, I am continuing to explore how glial and neuroimmune interactions have evolved unique and unexpected downstream biological activities by investigating the impact of these interactions across aging and disease, with a specific focus on how these affect cognitive function and contribute to neuropathological changes in degeneration.
Throughout my training, the support and guidance from mentors and collaborators has been instrumental in achieving my goals and pursuing innovative scientific questions. I am excited to provide the same level of training for other young scientists and to establish an inclusive, innovative, and highly collaborative research program here at Duke University.
Selected Publications
Scott-Hewitt N#, Mahoney M, Huang Y, Korte N, de Soysa Y, Wilton D, Knorr E, Mastro K, Chang A, Zhang A, Melville D, Schenone M, Hartigan C, Stevens B#. Microglial-derived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain. Cell 187 (16), 4193-4212. e24 PMID: 38942014. #Co-corresponding authors
Scott-Hewitt N*, Huang Y*, Stevens B. Convergent mechanisms of microglia-mediated synaptic dysfunction contribute to diverse neuropathological conditions. Ann NY Acad Sci (2023) doi: 10.1111/nyas.15010. PMID: 37272510. *These authors contributed equally
Scott-Hewitt N*, Perrucci F*, Morini R, Erreni M, Mahoney M, Witkowska A, Carey A, Faggiani E, Schuetz LT, Mason S, Tamborini M, Bizzotto M, Passoni L, Filipello F, Jahn R, Stevens B#, Matteoli M#. Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. EMBO J. 2020 Aug 17; 39(16):e105380. PMID: 32657463. *These authors contributed equally #Co-corresponding authors
Scott-Hewitt NJ, Folts CJ, Hogestyn JM, Piester G, Mayer-Pröschel M, Noble MD. Heterozygote galactocerebrosidase (GALC) mutants have reduced remyelination and impaired myelin debris clearance following demyelinating injury. Hum Mol Genet. 2017 08 01; 26(15):2825-2837. PMID: 28575206.
Folts CJ*, Scott-Hewitt N*, Pröschel C, Mayer-Pröschel M, Noble M. Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity. PLoS Biol. 2016 Dec; 14(12):e1002583. PMID: 27977664. *These authors contributed equally