Sambamurti Laboratory

Dr. Sambamurti's laboratory focuses on molecular mechanisms of degeneration and the development of prevention and treatment paradigms. Over the years, Dr. Sambamurti's laboratory has contributed to several major advances in our understanding of protein turnover related to Alzheimer's disease. He was a member of the Center on Aging at MUSC and served as a member of its executive committee. His studies range from basic analysis of transcriptional and post-transcriptional mechanisms of protein regulation to protein turnover at the in vitro, cellular, animal model, and clinical levels. These studies include the identification of the intracellular fragment of APP generated after γ-secretase cleavage and the development of a novel in vitro assay for the enzyme, identifying regulatory pathways for β-secretase, and determining the role of glycosylation in APP processing.

Our most recent studies have discovered a novel mechanism for the paradoxical increase in Aβ obtained at low doses of several γ-secretase inhibitors. Over the years, Dr. Sambamurti has secured grants from NIH, Foundations, and several corporations. Dr. Sambamurti founded and codirected the Carroll A. Campbell, Jr. neuropathology laboratory before transferring it to the pathology department. The human brain bank collected over 120 samples under his leadership and has expanded to double the number. Dr. Sambamurti has coauthored 118 Scopus-listed documents with 10052 citations and an H-index of 52. He has reviewed and served on the Editorial Boards of scientific journals, including JAD, CAR, and CAS, and participated in numerous grant review study sections, including NIH, NSF, DOD, ADDF, and Alzheimer Association. Dr. Sambamurti taught Medical Dental and Graduate level Neuroscience classes and has routinely conducted a course on Neurodegeneration.

Research:

Treating and preventing dementia can target the problem at several levels:
Occam's razor to avert progression to pathology and disease
Dietary Intervention and microbiota (Currently in progress)
RNA biology (miRNA, etc., in early stages)
APP inhibitors (Posiphen)
Anti-inflammatories (Thalidomide derivatives)

Phenotypic correction to manage the deficits
Anti-cholinesterase (Phenserine, Tolserine)
norepinephrine and Dopamine (Live biotherapeutics; currently in progress)

Sambamurti Laboratory Recent Publications (2020-current)

Huang M, Bargues-Carot A, Riaz Z, Wickham H, Zenitsky G, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG. Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson's Disease. Int J Mol Sci. 2022 Sep 16;23(18). doi: 10.3390/ijms231810808. Review. PubMed PMID: 36142718; PubMed Central PMCID: PMC9505762

Padhi P, Worth C, Zenitsky G, Jin H, Sambamurti K, Anantharam V, Kanthasamy A, Kanthasamy AG. Mechanistic Insights Into Gut Microbiome Dysbiosis-Mediated Neuroimmune Dysregulation and Protein Misfolding and Clearance in the Pathogenesis of Chronic Neurodegenerative Disorders. Front Neurosci. 2022;16:836605. doi: 10.3389/fnins.2022.836605. eCollection 2022. Review. PubMed PMID: 35281490; PubMed Central PMCID: PMC8914070.

Cui J, Ait-Ghezala G, Sambamurti K, Gao F, Shen Y, Li R. Sex-Specific Regulation of β-Secretase: A Novel Estrogen Response Element (ERE)-Dependent Mechanism in Alzheimer's Disease. J Neurosci. 2022 Feb 9;42(6):1154-1165. doi: 10.1523/JNEUROSCI.0864-20.2021. Epub 2021 Dec 13. PubMed PMID: 34903570; PubMed Central PMCID: PMC8824503.

Pappolla MA, Perry G, Fang X, Zagorski M, Sambamurti K, Poeggeler B. Indoles as essential mediators in the gut-brain axis. Their role in Alzheimer's disease. Neurobiol Dis. 2021 Aug;156:105403. doi: 10.1016/j.nbd.2021.105403. Epub 2021 Jun 1. Review. PubMed PMID: 34087380.

Ray B, Maloney B, Sambamurti K, Karnati HK, Nelson PT, Greig NH, Lahiri DK. Correction: Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer's disease. Transl Psychiatry. 2020 Mar 2;10(1):81. doi: 10.1038/s41398-020-0757-2. PubMed PMID: 32123156; PubMed Central PMCID: PMC7052148.

Ray B, Maloney B, Sambamurti K, Karnati HK, Nelson PT, Greig NH, Lahiri DK. Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer's disease. Transl Psychiatry. 2020 Feb 3;10(1):47. doi: 10.1038/s41398-020-0709-x. PubMed PMID: 32066688; PubMed Central PMCID: PMC7026402.