Laboratory of Georgette Kanmogne, PhD, MPH
Durham Research Center 4060
985800 Nebraska Medical Center
Omaha, NE 68198-5800
Keywords: HIV-1, Blood-Brain Barrier, Micro vascular endothelial cells (MVEC), tight junction proteins, epigenetics, humanized mice, TLR3, HIV-1 clade diversity
UNMC Today | February 6, 2018
Chemically modified drug shows promise for HIV treatment, elimination
The blood brain barrier (BBB) is an interface layer between the blood stream and central nervous system. The major components of BBB consist of microvascular endothelial cells (MVEC) sealed together by tight and adherent junctions proteins, basement membrane, pericytes, and overlying astrocytes end feet. HIV-associated neurocognitive disorder (HAND) is a spectrum of neurocognitive dysfunction associated with HIV infection. HIV-1 crosses the BBB during primary infection and enters the brain to cause persistent CNS HIV-1 infection that leads to HAND. Certain strains of HIV-1 may have differential mechanisms in inducing BBB inflammation, neurocognitive impairment, and influence viral eradication strategies. It is still unknown what are the roles of HIV-1 viral proteins, adhesion molecules, cytokines and chemokine receptors in the trans-endothelial migration of HIV-1.
My current research focuses on understanding the molecular mechanisms/signaling/epigenetics associated with HIV-1 infection and BBB dysfunction using various in vitro and humanized mice models, and explore how the viral clade diversity influence this process.
- Brenza TM, Schlichtmann BW, Bhargavan B, Vela Ramirez JE, Nelson RD, Panthani MG, McMillan JM, Kalyanaraman B, Gendelman HE, Anantharam V, Kanthasamy AG, Mallapragada SK, Narasimhan B, Kanmogne GD. Biodegradable polyanhydride-based nanomedicines for blood to brain drug delivery. J Biomed Mater Res A. 2018 Nov;106(11):2881-2890. PMID: 30369055
- Sillman B, Bade AN, Dash PK, Bhargavan B, Kocher T, Mathews S, Su H, Kanmogne GD, Poluektova LY, Gorantla S, McMillan J, Gautam N, Alnouti Y, Edagwa B, Gendelman HE. Creation of a long-acting nanoformulated dolutegravir. Nat Commun. 2018 Feb 6;9 (1):443. PMID: 29402886
- Bhargavan B, Kanmogne GD. Toll-Like Receptor-3 Mediates HIV-1-Induced Interleukin-6 Expression in the Human Brain Endothelium via TAK1 and JNK Pathways: Implications for Viral Neuropathogenesis. Mol Neurobiol. 2018 Jul;55 (7):5976-5992. PMID: 29128906
- Biju Bhargavan and Georgette D. Kanmogne. Differential Mechanisms of Inflammation and Endothelial Dysfunction by HIV-1 Subtype-B and Recombinant CRF02_AG Tat Proteins on Human Brain Microvascular Endothelial Cells: Implications for Viral Neuropathogenesis. Molecular Neurobiology, 2017, Online first: doi:10.1007/s12035-017-0382-0. PMID: 28127697.
- Bhargavan B, Woollard SM, Kanmogne GD. Toll-like receptor-3 mediates HIV-1 transactivation via NFκB and JNK pathways and histone acetylation, but prolonged activation suppresses Tat and HIV-1 replication. Cell Signal. 2016, 28(2):7-22. PMID: 26569339.
- Bhargavan B, Woollard SM1, Kanmogne GD. Data in support of NFκB and JNK pathways involvement in TLR3-mediated HIV-1 transactivation, expression of IL-6 and transcription factors associated with HIV-1 replication. Data Brief. 2015, 6:345-51. PMID: 26862581.
- Woollard SM, Bhargavan B, Yu F, Kanmogne GD. Differential effects of Tat proteins derived from HIV-1 subtypes B and recombinant CRF02_AG on human brain microvascular endothelial cells: implications for blood-brain barrier dysfunction. J Cereb Blood Flow Metab. 2014,34(6):1047-59. PMID: 24667918.
- Bhargavan B, Fatma N, Chhunchha B, Singh V, Kubo E, Singh DP. LEDGF gene silencing impairs the tumorigenicity of prostate cancer DU145 cells by abating the expression of Hsp27 and activation of the Akt/ERK signaling pathway. Cell Death Dis. 2012;3:e316. doi: 10.1038/cddis.2012.57. PMID: 22647853.
- Bhargavan B, Chhunchha B, Fatma N, Kubo E, Kumar A, Singh DP. Epigenetic repression of LEDGF during UVB exposure by recruitment of SUV39H1 and HDAC1 to the Sp1-responsive elements within LEDGF promoter CpG island. Epigenetics. 2013, 8(3):268-80. PMID: 23386123.
- Singh DP, Bhargavan B, Chhunchha B, Kubo E, Kumar A, Fatma N. Transcriptional protein Sp1 regulates LEDGF transcription by directly interacting with its cis-elements in GC-rich region of TATA-less gene promoter. PLoS One. 2012, 7(5):e37012. PMID: 22615874.
- Bhargavan B, Singh D, Gautam AK, Mishra JS, Kumar A, Goel A, Dixit M, Pandey R, Manickavasagam L, Dwivedi SD, Chakravarti B, Jain GK, Ramachandran R, Maurya R, Trivedi A, Chattopadhyay N, Sanyal S. Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats: evidence for estrogen receptor β-mediated osteogenic action of medicarpin. J Nutr Biochem. 2012, 23(1):27-38. PMID: 21333515.
- Bhargavan B, Gautam AK, Singh D, Kumar A, Chaurasia S, Tyagi AM, Yadav DK, Mishra JS, Singh AB, Sanyal S, Goel A, Maurya R, Chattopadhyay N. Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. J Cell Biochem. 2009, 108(2):388-99. PMID: 19598169.
- Gautam AK*, Bhargavan B*, Tyagi AM, Srivastava K, Yadav DK, Kumar M, Singh A, Mishra JS, Singh AB, Sanyal S, Maurya R, Manickavasagam L, Singh SP, Wahajuddin W, Jain GK, Chattopadhyay N, Singh D. Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats. J Nutr Biochem. 2011, 22(4):318-27 (*Equal first author). PMID: 20579866.
- Pandey R, Gautam AK, Bhargavan B, Trivedi R, Swarnkar G, Nagar GK, Yadav DK, Kumar M, Rawat P, Manickavasagam L, Kumar A, Maurya R, Goel A, Jain GK, Chattopadhyay N, Singh D. Total extract and standardized fraction from the stem bark of Butea monosperma have osteoprotective action: evidence for the nonestrogenic osteogenic effect of the standardized fraction. Menopause. 2010,17(3):602-10. PMID: 20395887.
Additional Publications in PubMed.