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Research Interests

Neuroinflammation, DNA damage, oxidative stress, and mitochondrial dysfunction. Cellular mechanisms, molecular mechanisms, cognitive aspects, and genetic factors involved in neuroinflammation in pathogenesis and progression of cancer, Alzheimer’s disease (AD), and other neurodegenerative diseases. Early events in AD pathogenesis. The role of immunological biomarkers for early detection in AD.

Current Projects

Roles of antioxidant depletion, oxidative stress, and lipid peroxidation in Alzheimer’s Disease pathogenesis and progression.

This funded project is focused on the role of Vitamin A homeostasis in Alzheimer’s disease (AD). We hypothesize that chronic inflammation within the brain contributes to neurodegeneration and learning and memory deficits. An upsurge in neuroinflammation, mitochondrial dysfunctions and oxidative stress are the well-known precursors for developing AD. Neuronal stress, including the formation of amyloid b aggregates, glial activation, mitochondrial dysregulation, and defective mitochondrial functionality, produce excess reactive oxygen species (ROS) that damage proteins, lipids, and DNA. Dietary antioxidants (AOs) normally scavenge excess ROS, preventing oxidative stress.  All-trans retinoic acid (ATRA) is a bioactive vitamin A derivative that plays a key role in the development and maintenance of the central nervous system. RA regulation of target genes is fundamental for optimal brain function such as synaptic plasticity, learning and memory. ATRA has various properties that can interact with key pathophysiological mechanisms of AD. See also Lawrence web page.

“Reverse aging” age-related epigenetic changes to DNA to prevent Alzheimer’s Disease-related learning deficits.

Prominent roles of oxidative stress in Alzheimer’s disease (AD) imply that antioxidant depletion is a critical mechanism occurring at prodromal stages. Yet, to date, clinical trials involving antioxidant supplementation have paradoxically failed. Several histone deacetylases (HDACs) have been shown to be upregulated, providing evidence that deacetylation is a molecular mechanism that leads to transcriptional repression in AD. We hypothesize that HDAC inhibition is required to restore function of key transcription factors that support hippocampal-dependent learning. See also Lawrence web page.

The role of Rlip in cancer and Alzheimer’s disease. 

Rlip is a stress-protective ATPase of the mercapturic acid pathway that couples clathrin-dependent endocytosis with the efflux of glutathione-electrophile conjugates. Rlip is evolutionarily highly conserved across species and is ubiquitously expressed in all tissues, including brain regions, the cerebral cortex and hippocampus where highly active neuronal metabolisms render the cells highly susceptible to intracellular oxidative damage. We showed Rlip was gradually decreased in post mortem AD brains, being lowest in Braak stage IV-V. Recent research from our lab revealed that reduced levels of Rlip76 induce oxidative stress, mitochondrial dysfunction and synaptic damage, leading to molecular and behavioral phenotypes resembling late-onset AD. Depleted Rlip may exacerbate oxidative stress, mitochondrial dysfunction and synaptic damage in AD. 

Recently completed grants:

DOD W81XWH-18-1-0534   (Role: Co-I)
08/15/18 - 8/14/2021
Prevention of Breast Cancer by Haploinsufficiency of RALBP1
The proposed study was to determine if a Rlip depletion strategy can be used in breast cancer prevention, and to determine how Rlip regulates the expression of key oncogenes and tumor suppressors.
AbSynapTex PAS-17-065 (Role: PI)                                                                                                                     07/2019 -12/31/2019
Small Inhibitor Therapeutic Target for Alzheimer’s disease. The purpose of this subcontract with abSynapTex LLC was to study the efficacy of a small molecule ‘DDQ’ in amyloid beta precursor protein transgenic mice, an Alzheimer’s disease mouse model. 

Selected Publications:

• P Hemachandra Reddy, Sudhir Kshirsagar, Chhanda Bose, Jangampalli Adi Pradeepkiran, Ashly Hindle, Sharda P Singh, Arubala P Reddy, Javaria Baig. Rlip Reduction Induces Oxidative Stress and Mitochondrial Dysfunction in Mutant Tau-Expressed Immortalized Hippocampal Neurons: Mechanistic Insights. Cells. 2023 Jun PMID: 37371116.
• Reddy PH, Kshirsagar S, Bose C, Pradeepkiran JA, Hindle A, Singh SP, Reddy AP. Rlip overexpression reduces oxidative stress and mitochondrial dysfunction in Alzheimer's disease: Mechanistic insights. Biochim Biophys Acta Mol Basis Dis. 2023 May 22;1869(7):166759. PMID: 37225106.
• Pulak R Manna, Chhanda Bose, P Hemachandra Reddy. Downregulation of StAR driven neurosteroid biosynthesis as a distinctive feature in the brains of Alzheimer's disease patients. Biochim Biophys Acta Mol Basis Dis.  2023 Aug;1869(6):166757. PMID: 37209874.
• Ashly Hindle, Sharda P Singh, Jangampalli Adi Pradeepkiran, Chhanda Bose, Murali Vijayan, Sudhir Kshirsagar, Neha A Sawant, P Hemachandra Reddy. Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer's Disease? Int J Mol Sci. 2022 May 29;23(11):6098. PMID: 35682775.
• Ashly Hindle, Chhanda Bose, Jihyun Lee, Philip T Palade, Christopher J Peterson, P Hemachandra Reddy, Sanjay Awasthi, Sharda P Singh. Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels. Cancers (Basel). 2022 Jan 21;14(3):527. PMID: 35158795.
• Subodh Kumar, Erika Orlov, Prashanth Gowda, Chhanda Bose, Russell H. Swerdlow, Debomoy K. Lahiri and P Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease. Hemachandra Reddy. NPJ Genomic Medicine 2022, 47, PMID: 35941185.
• Morton Hallie, Basu Tanisha, Bose Chhanda, Reddy, P. Hemachandra. Impact of Chronic Conditions and Dementia in Rural West Texas: A Healthy Aging Study. Review Article. Journal of Alzheimer's Disease, vol. 87, no. 1, pp. 33-49, 2022. PMID: 35275552.
• Bose Chhanda, Hindle A, Lee J, Kopel J, Tonk S, Palade PT, Singhal SS, Awasthi S, Singh SP. Anticancer Activity of Ω-6 Fatty Acids through Increased 4-HNE in Breast Cancer Cells.  Cancers (Basel). 2021 Dec 20;13(24):6377. PMID: 34944997.
• Vijayan M, George M, Bunquin LE, Bose C, Reddy PH. Protective effects of a small-molecule inhibitor DDQ against tau-induced toxicities in a transgenic tau mouse model of Alzheimer's disease.  Hum Mol Genet. 2021 Sep 24: ddab285. PMID: 34559191.
• Marija Petkovic, Ermelindo C Leal, Ines Alves, Chanda Bose, Philip T Palade, Preeti Singh, Sanjay Awasthi, Elisabet Børsheim, Louise T Dalgaard, Sharda P Singh, Eugenia Carvalho. Dietary supplementation with sulforaphane ameliorates skin aging through activation of the Keap1-Nrf2 pathway. J Nutr Biochem.  2021 Jul 14; 98:108817. PMID: 34271100.
• Vijayan M, Bose Chhanda, Reddy PH. Anti-brain Aging Effects of Small Molecule Inhibitor DDQ. Mol Neurobiol. 2021. Epub 2021/03/27. PMID: 33768469.
• Vijayan M, Bose Chhanda, Reddy PH. Protective effects of a small molecule inhibitor, DDQ against amyloid beta in Alzheimer's disease. Mitochondrion. 2021; 59:17-29. Epub 2021/04/12. 2021. PMID: 33839321.
• Jun SR, Cheema A, Bose Chhanda, Boerma M, Palade PT, Carvalho E, Awasthi S, Singh SP. Multi-Omic Analysis Reveals Different Effects of Sulforaphane on the Microbiome and Metabolome in Old Compared to Young Mice. Microorganisms. 2020;8(10). Epub 2020/10/03. PubMed PMID: 33003447.
• Chhanda Bose, Yadav S, Singhal SS, Singhal J, Hindle A, Lee J, Cheedella NKS, Rehman S, Rahman RL, Jones C, Darden M, Palade PT, Berz D, Singh SP, Awasthi S. Rlip Depletion Suppresses Growth of Breast Cancer. Cancers (Basel). 2020;12(6). PMID: 32498332.
• Chhanda Bose, Alves I, Singh P, Palade PT, Carvalho E, Børsheim E, Jun S-R, Cheema A, Boerma M, Awasthi S, Singh SP. Sulforaphane prevents age‐associated cardiac and muscular dysfunction through Nrf2 signaling. Aging Cell. 2020; Nov;19(11): e13261. PMID: 33067900.
• Bose, Chhanda; Singh, S.P.; Igid, H.; Green, W.C.; Singhal, S.S.; Lee, J.; Palade, P.T.; Rajan, A.; Ball, S.; Tonk, V.; Hindle, A.; Tarbox, M.; Awasthi, S. Topical 2′-Hydroxyflavanone for Cutaneous Melanoma. Cancers (2019), 11, 1556.
• Meenakshisundaram Balasubramaniam, Paul A Parcon, Chhanda Bose, Ling Liu, Richard A Jones, Martin R Farlow, Robert E Mrak, Steven W Barger, W Sue T Griffin. Interleukin-1β drives NEDD8 nuclear-to-cytoplasmic translocation, fostering parkin activation via NEDD8 binding to the P-ubiquitin activating site. J Neuroinflammation. 2019 Dec 27;16(1):275. PMID: 31882005.
• Chhanda Bose, Sanjay Awasthi, Rajendra Sharma, Helen Benes, Martin Hauer Jensen, Marjan Boerma, Sharda P Singh. Sulforaphane potentiates anticancer effects of doxorubicin and     attenuates its cardiotoxicity in a breast cancer model. PLoS One 2018 13(3): PMID: 29518137.
• Chhanda Bose, Sudhir V. Shah, Oleg K. Karaduta, and Gur P. Kaushal. (2016) Carbamylated low-density lipoprotein (cLDL)-mediated induction of autophagy and its role in endothelial cell injury. PLoS One Dec 14; 11(12): e0165576. PMID: 27973558.
• Bose Chhanda, Megyesi JK, Shah SV, Hiatt KM, Hall KA, Karaduta O, Swaminathan S. (2015) Evidence suggesting a role of iron in a mouse model of nephrogenic systemic fibrosis. PLoS One 10(8): e0136563. PMID: 26305890.
• Shah SV, Shukla AM, Bose Chhanda, Basnakian AG, Rajapurkar M. (2015) Recent advances in understanding the pathogenesis of atherosclerosis in CKD patients. J Ren Nutr 25(2):205-208. PMID: 25556310.
• Swaminathan S, Bose Chhanda, Shah SV, Hall KA, Hiatt KM. (2013) Gadolinium contrast agent-induced CD163+ 1 ferroportin+ osteogenic cells in nephrogenic systemic fibrosis. Am J Pathol 183(3):796-807. PMID: 23867799.
• Bose Chhanda, Udupa KB. (2008) Erythropoietin enhancement of rat pancreatic tumor cell proliferation requires the activation of ERK and JNK signals. Am J Physiol Cell Physiol 294 (2):394-405. PMID: 18550701.
• Bose Chhanda, Zhang H, Udupa KB, Chowdhury P. (2005) Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effect on proliferation and secretion. Am J Physiol Gastrointest Liver Physiol 289: G926-G934. PMID: 16051920
• Udupa KB, Bose Chhanda. (2005) Identification of erythroid cell stimulating factor as a unique protein. Quiescin6: role in erythropoiesis. Blood 106(11):4270.
• Bose Chhanda, Chidambaram B, Udupa KB. (2005) Age related alteration in hepatic acyl-CoA: cholesterol acyltransferase and its relation to LDL receptor and MAPK. Mech Aging Dev 126:740-751. PMID: 15888329.
• Bose Chhanda, Bhuvaneswaran C, Udupa KB (2004). Altered mitogen activated protein kinase signal transduction in human skin fibroblasts during in vitro aging: Differential expression of low-density protein receptor. J Gerontol A Biol Sci Med Sci 59(2):126-135. PMID: 14999025.
• Bose Chhanda, Guo J, Zimniak L, Srivastava SK, Singh SP, Zimniak P, Singh SV. (2002) Critical role of allyl groups and disulfide chain in induction of Pi class glutathione transferase in mouse tissues in vivo by diallyl disulfide, a naturally occurring chemo preventive agent in garlic. Carcinogenesis 23(10):1661-1665. PMID: 12376475.