Chemically modified drug shows promise for HIV treatment, elimination
Epstein, Bade are NU Presidential Graduate Fellows
Student Spotlight - Meet Aditya Bade
New 'Help Line" will assist international students
Studies of HIV pathogenesis, antiretroviral therapy (ART) and ART associated toxicity using murine and in vitro models are my focal areas of research. I have been extensively involved in development of long acting anti-retroviral injectables, and have investigated mechanisms underlying ART, specifically dolutegravir (DTG), associated toxicity on the brain. My research is also focused on utilizing bioimaging modality (MRI) to study neuropathology associated with neurodegenerative disorders and drugs of abuse and to determine the outcome of treatments.
1) Development of long acting nanoformulations of antiretroviral prodrugs
In one of the ongoing project, our group is focused on transforming currently available anti-retroviral therapy (ART) into long acting slow effective release ART (LASER ART). Such a long-acting ART regimens will allow monthly injections with an ability to maintain consistent drug levels at effective concentrations in plasma and in tissues, This strategy would improve treatment outcomes. I am, particularly, involved in investigating efficacy and toxicity of ART and LASER ART in different in vitro systems (T-cells and Macrophages) and rodents (in vivo). I have evaluated detailed pharmacokinetic profiles of native anti-retroviral drugs and respective long-acting nanoformulations in rodents (mice and rats) with both sexes (male and female). In addition, I have examined anti-retroviral profiles of these nanoformulations as a pre-exposure prophylaxis or as a treatment regimens by using HIV- infected humanized mice [NOD/scid-IL-2Rγcnull (NSG) and human adult peripheral blood lymphocytes (hu-PBL) mice].
2) Examine links between in utero exposure to integrase strand transfer inhibitors (INSTIs) and fetal neurodevelopment
In another project, my research is focused on examining potential mechanisms underlying adverse effects on the fetal brain development that follows in utero exposure to integrase strand transfer inhibitors, and potential therapies to attenuate such adverse effects. The research employs cross-validating approaches including histopathological, immunochemical, transcriptomic, metabolomics, bioimaging and behavioral tests. The overall objective of this project is to improve birth outcomes of children born to women receiving antiretroviral drugs (ARVs) at the time of conception.
I developed and implemented the applications of Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) in understanding the pathology underlying neurodegenerative diseases and in determining treatment outcomes in murine models. Moreover, in collaboration, we developed rodent 3D brain atlases (mice and rats), and made these atlases available to researchers worldwide through Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC, https://www.nitrc.org/users/adityabade/). Herein, we identified 41 brain structures for mice brain atlas and 40 brain structures for rat brain atlas. These atlases provide a unique opportunity for longitudinal unbiased region specific examination.
- 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. PubMed PMID: 29402886; PubMed Central PMCID: PMC5799307.
- Gnanadhas DP, Dash PK, Sillman B, Bade AN, Lin Z, Palandri DL, Gautam N, Alnouti Y, Gelbard HA, McMillan J, Mosley RL, Edagwa B, Gendelman HE, Gorantla S. Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs. J Clin Invest. 2017 Mar 1;127(3):857-873. PubMed PMID: 28134625; PubMed Central PMCID: PMC5330738.
- Kevadiya BD, Bade AN, Woldstad C, Edagwa BJ, McMillan JM, Sajja BR, Boska MD, Gendelman HE. Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging. Acta Biomater. 2017 Feb;49:507-520. PubMed PMID: 27916740; PubMed Central PMCID: PMC5501313.
- Bade AN, Gendelman HE, Boska MD, Liu Y. MEMRI is a biomarker defining nicotine-specific neuronal responses in subregions of the rodent brain. Am J Transl Res. 2017;9(2):601-610. PubMed PMID: 28337287; PubMed Central PMCID: PMC5340694.
- Bade AN, Gorantla S, Dash PK, Makarov E, Sajja BR, Poluektova LY, Luo J, Gendelman HE, Boska MD, Liu Y. Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice. Mol Neurobiol. 2016 Jul;53(5):3286-3297. PubMed PMID: 26063593; PubMed Central PMCID: PMC4676748.
- Olson KE, Bade AN, Schutt CR, Dong J, Shandler SJ, Boska MD, Mosley RL, Gendelman HE, Liu Y. Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease. Neurotherapeutics. 2016 Jul;13(3):635-46. PubMed PMID: 27329163; PubMed Central PMCID: PMC4965412.
- Sajja BR, Bade AN, Zhou B, Uberti MG, Gorantla S, Gendelman HE, Boska MD, Liu Y. Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2Rγc(null) Mouse Brain Atlas. J Neuroimmune Pharmacol. 2016 Mar;11(1):133-41. PubMed PMID: 26556033; PubMed Central PMCID: PMC4871948.
- Bade AN, Zhou B, Epstein AA, Gorantla S, Poluektova LY, Luo J, Gendelman HE, Boska MD, Liu Y. Improved visualization of neuronal injury following glial activation by manganese enhanced MRI. J Neuroimmune Pharmacol. 2013 Sep;8(4):1027-36. PubMed PMID: 23729245; PubMed Central PMCID: PMC3746563.