Nirmala Nirinjini Naidoo, Ph.D.

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Research Professor of Medicine (Sleep Medicine)
Department: Medicine
Graduate Group Affiliations

Contact information
Translational Research Laboratories
125 South 31st Street, Suite 2100
Philadelphia, PA 19104-3403
Office: 215-746-4811
Fax: 2156-746-4814
B.S. (Biochemistry and Microbiology)
University of Durban-Westville, South Africa, 1982.
B.S. (Biochemistry, Honors)
University of Durban-Westville, South Africa, 1984.
M.S. (Biochemistry)
University of Durban-Westville, South Africa Dissertation: An Investigation of the Preparation and Interaction of Glycoprotein-DNA Conjugates with Eukaryotic Cell Receptors, 1986.
Ph.D. (Chemistry)
University of Pennsylvania Dissertation: Structure-Function Studies on Alpha-1-Antichymotrypsin, 1994.
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Description of Research Expertise

Dr. Naidoo’s research focuses on proteostatic mechanisms underlying age related changes in sleep and wake regulation. She has established that sleep loss or sleep disturbances induce endoplasmic reticulum (ER) stress that up-regulates an adaptive homeostatic signaling pathway, the unfolded protein response (UPR). She has demonstrated that the UPR and proteostasis become impaired with aging. ER stress and the UPR are critical to the initiation and integration of pathways of inflammation as well as in the etiology of neurodegenerative diseases. Using two model systems, mouse and Drosophila, to carry out research on proteostasis mechanisms her group is unraveling the role of the UPR in behavior and pathologies. Her work has demonstrated that restoring proteostasis rescues the sleep phenotype in aged animals and cognition in aged and Alzheimer's disease mouse models. She has expanded her research to investigate the role of proteostasis mechanisms in Alzheimer's disease and in co-occurring conditions in Down Syndrome. Other research in her group is focused on the role of the synaptic scaffolding protein, Homer and its interaction with metabotropic glutamate receptors in the maintenance of wakefulness.

Selected Publications

Brendan T. Keenan, Ewa Strus, Raozhou Lin, May Chan, Jie Lian, Raymond Galante, Paul Worley,Allan I. Pack, Nirinjini Naidoo: mGluR1/5 Interactions with Prolyl Isomerase (Pin1) And Homer1a Mediate Sleep-Wake Behavioral Changes. iScience DOI: 10.2139/ssrn.4419231 2023.

Hafycz JM, Strus E, Naidoo N: Reducing ER stress with chaperone therapy reverses sleep fragmentation and cognitive decline in aged mice. Aging Cell 21(6): e13598, Jun 2022.

Lin R, Learman LN, Bangash MA, Melnikova T, Leyder E, Reddy SC, Naidoo N, Park JM, Savonenko A, Worley PF: Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome Cell Reports 37(7): 110014, Nov 2021.

Ly S, Lee D, Strus E, Prober D, Naidoo N: Evolutionarily conserved regulation of sleep by the protein translational regulator PERK. Current Biology 30(9): 1639-1648, May 2020.

Zhu J, Hafycz J, Keenan BT, Guo X, Pack A, Naidoo N: Acute sleep loss upregulates the synaptic scaffolding protein, Homer1a, in non-canonical sleep/wake brain regions, claustrum, periform and cingulate cortices. Front Neurosci 14: 188, Mar 2020.

Ly S, Strus E, Naidoo N: Genetic disruption of the putative binding site for Homer on DmGluRA reduces sleep in Drosophila. Sleep 43(1): zsz190, Jan 2020.

Ly SL, Naidoo N: Loss of DmGluRA exacerbates age-related sleep disruption and reduces lifespan. Neurobiology of Aging 80: 83-90, Aug 2019.

Chellapa K, Perron I, Naidoo N*, Baur J* (co-senior/corresponding author): The leptin sensitizer celastrol reduces age-associated obesity and modulates behavioral rhythms. Aging Cell 18(e): e12874, Jun 2019.

Naidoo N, Zhu J, Galante RJ, Lian J, Strus E, Lee A, Keenan BT, Pack AI: Reduction of the molecular chaperone BiP accentuates the effect of aging on sleep-wake behavior. Neurobiology of Aging 69: 10-25, Sept 2018.

Ly S, Pack AI, Naidoo N: The neurobiological basis of sleep: insights from Drosophila. Neuroscience and Biobehavioral Reviews 87: 67-86, Apr 2018.

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Last updated: 01/05/2024
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