Search
Loading Complete
Amanda M. Brown

Amanda M. Brown, PhD

Highlights

Languages

  • English

Gender

Female

Johns Hopkins Affiliations:

  • Johns Hopkins School of Medicine Faculty

About Amanda M. Brown

Primary Academic Title

Professor of Neurology

Background

Amanda M. Brown is the Fannie Gaston-Johansson Professor Neurology and Neuroscience at the Johns Hopkins University School of Medicine. She completed a Bachelor’s degree in Biochemistry at the University of California Riverside and obtained a PhD in Microbiology and Immunology at the Albert Einstein College of Medicine where she was the first to identify a new type of protein secretion pathway of mycobacteria later found in many other pathogenic bacteria. During postdoctoral training she developed a novel recombinant HIV reporter virus to interrogate HIV persistent and latent replication of human macrophages at the level of single cells. Moreover, the approach led to the identification of osteopontin as a key regulator of HIV-induced neuroinflammation.

 

Currently, her R01-funded research uses humanized mice, human tissues, cellular reprogramming, and the latest advances in single-cell technologies and neuroimaging to study the behavioral, and neuropathologic consequences and to identify the molecular mechanisms by which HIV disrupts CNS homeostasis (detailed below). Throughout her career she has been dedicated to training the next generation of researchers from across the training lifespan and different backgrounds. To date she has secured over $6.5 million in NIH-funded and philanthropic funds to support these training efforts.

CV

Additional Academic Titles

Professor of Neuroscience

Research Summary

Research in the Brown lab focuses on how breach of the blood-brain-barrier by viral pathogens like the human immunodeficiency virus type 1 (HIV-1), alters brain homeostasis. Central to this research is acquiring a detailed mechanistic understanding of the pathways leading to sustained neuroinflammation. HIV-1 robustly infects microglia and macrophages, but not neurons and to a lesser extent, astrocytes.

Today, antiviral treatment, has transformed HIV infection allowing people to live longer. However, HIV exacerbates many of the comorbid conditions associated with aging and up to 50% of people with HIV can experience neurologic complications.

None of the current therapies block HIV transcription. The Brown lab is testing the hypothesis that ongoing systemic low-level HIV gene expression drives chronic activation of pro-inflammatory signaling which impairs cognition. The ultimate goals of the research are to identify and understand the key gene expression networks involved. With such knowledge, new treatments to ameliorate HIV-associated cognitive comorbidities can be developed.

The lab’s experimental approach to modeling HIV-induced neuroinflammation include the use of physiologically relevant primary cell culture models, humanized mice (hu-mice) that reflect HIV systemic or brain infection, and the use of human brain tissues to validate findings. Well-validated molecular, as well as leading-edge tools in neuroscience including rodent PET- and MRI-neuroimaging, sn-RNA-seq, multicolor immunofluorescence and associated analytic tools like Imaris are used. The lab has developed protocols to safely assess memory, locomotor and motivational behaviors in the immunodeficient hu-mice models.

Research over the past five years in the Brown lab has implicated the multifunctional protein, osteopontin (OPN), which is encoded by the SPP1 gene, as a sensor and regulator of neuroinflammation in HIV-hu-mice. OPN/SPP1 has long been described in neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, multiple sclerosis (MS), and fronto-tempro dementia as a putative predictive biomarker.  However, except for MS, there remains a profound lack of insight into OPN/SPP1’s mechanistic function (s) in the brain. Exciting recent findings from the Brown laboratory and their collaborators indicate that OPN/SPP1 is a master regulator of neuroinflammatory signaling. Ongoing studies are investigating the impact of OPN/SPP1 on cognition, dopaminergic-glial signaling, white matter integrity, and immune cell trafficking.

Mohamed M, Skolasky RL, Zhou Y, Ye W, Brasic JR, Brown AM, Pardo CA, Barker PB, Wong DF, and N Sacktor. Beta-amyloid (Abeta) uptake by PET imaging in older HIV+ and HIV- individuals. J. Neurovirology 2020; https://doi.org/10.1007/s13365-020-00836-1.

Mahmud F, Boucher T, Liang SJ, and Brown AM. Osteopontin and integrin mediated modulation of post-synapses in HIV envelope glycoprotein exposed hippocampal neurons. Brain Sciences 2020; 10(6):346  https://doi.org/10.3390/brainsci10060346. PMID: 32512754

Mahmud F, Du Y, Greif E, Boucher T, Dannals RF, Mathews WB, Pomper MG, Sysa-Shah P, Metcalf Pate KA, Lyons C, Carlson B, Chacona M, and Brown AM. Osteopontin/secreted phosphoprotein-1 behaves as a molecular brake regulating the neuroinflammatory response to chronic viral infection. J. Neuroinflammation. 17: 273 2020 doi: 10.1186/s12974-020-01949-4.

Mahmud F, Du Y, Greif E, Boucher T, Metcalf Pate KA, Lyons C, Carlson B, and Brown AM. Complex interactions between human immunodeficiency virus type-1, sex, and osteopontin influence viral and leukocyte persistence in tissues. F. Virology 2021 https://doi.org/10.3389/fviro.2021.690360

Boucher T, Liang SJ, and Brown AM. Advancing Basic and Translational Research to Deepen Understanding of the Molecular Immune-Mediated Mechanisms Regulating Long-Term Persistence of HIV-1 in Microglia in the Adult Human Brain. J Leukocyte Biol. 2022; 112:1223-1231.

      Yim A, Smith C, Chacona M, and Brown AM. Osteopontin/secreted phosphoprotein-1: a homeostatic sensor and regulator at the neuro-immune axes. Immunological Reviews 2022. http://doi.org/10.1111/imr.13081

Robinson JA, Mahmud FJ, Greif E, Toribio M, Zanni MV, Brown AM and TH Burdo. Osteopontin (OPN) is an Integral mediator of interstitial fibrosis in models of HIV infection. Journal of Infectious Disease 2023:122-132.

Argandona CL and Brown AM. Microglial- neuronal crosstalk in chronic viral infection through mTOR, SPP1/OPN and inflammasome pathway signaling. Front. Immunol. 2024; 15: https://doi.org/10.3389/fimmu.2024.1368465

Selected Publications

    1. Calixto-Hope Lucas; Mathilde Calvez; Roshni Babu; Amanda Brown Altered subcellular localization of the NeuN/Rbfox3 RNA splicing factor in HIV-associated neurocognitive disorders (HAND) Neuroscience Letters. 2014;558:97-102.
    2. Roshni Babu; Amanda Brown A consensus surface activation marker signature is partially dependent on human immunodeficiency virus type 1 Nef expression within productively infected macrophages Retrovirology. 2013;10(1).
    3. Charlene E. Gamaldo; Alyssa Gamaldo; Jason Creighton; Rachel E. Salas; Ola A. Selnes; Paula M. David; Gilbert Mbeo; Benjamin S. Parker; Amanda Brown; Justin C. McArthur; et al. Evaluating sleep and cognition in HIV Journal of Acquired Immune Deficiency Syndromes. 2013;63(5):609-616.
    4. Brown, A., Use of a macrophage-tropic GFP-tagged human immunodeficiency virus type 1 (HIV-1) to study viral reservoirs. Methods in Mol. Biol 2009;515:165-175.
    5. Grab, D, Garcia-Garcia, J. C., Nikolskaia, O V., Kim, Y. V., Brown, A., Pardo, C. A., Zhang, Y., Becker, K. G., Wilson, B. A., de A Lima, A P., Scharfstein, J., and J. S. Dumler. Protease activated receptor signaling is required for African typanosome traversal of human brain microvascular endothelial cells. PLOS Neglected Tropical Diseases 2009: 3(7):e479.
    6. Hammoud DA, Endres C.J., Hammond E., Uzuner O., Brown A., Nath A., Kaplin A.I., Pomper M.G. Imaging serotonergic transmission with [(11)C]DASB-PET in depressed and non-depressed patients infected with HIV. Neuroimage 2009; 49:2588-2595.
    7. Brown, A., Shiramizu, B., Nath, A., Valerie Wojna. 2011. Translational research in neuroAIDS: A neuroimmune pharmacology related CME course, J. Neuroimmun. Pharmacol. 6:80-88;Epub 2010 May 25.
    8. Brown, A., Islam, T., Adams, R., Nerle, S., Kamara, M., Eger, C., Marder, K., Cohen, B., Schifitto, G., McArthur, J., Sacktor, N., and C. Pardo. 2011. Osteopontin enhances HIV-1 replication and is increased in the brain and cerebrospinal fluid of HIV-infected individuals. J. Neurovirology 17:382-392.
    9. Brown, A., Sacktor, N., Marder, K., Cohen, B., Schifitto, G., Skolasky, R., Creighton, J., Guo, L and J. McArthur. 2012. CCL3L1 gene copy number in individuals with and without HIV-associated neurocognitive disorder. Current Biomarker Findings 2012; 2: 1-6.

Lectures & Presentations

  • Relocalization of HIV-Gag+CD81+ virus containing compartments to the plasma membrane of primary human macrophages., 50th American Society for Cell Biology Conference, The Society for Leucocyte Biology, Philadelphia, Pennsylvania, 1/1/10
  • Research tools to isolate and study HIV-infected macrophage subpopulations., The Second Annual Symposium on Virology and Laser Microdissection. Integrated Research Facility, Division of Clinical Research/NIAID/NIH, Bethesda, Maryland, 5/1/09
  • The role of osteopontin in HIV neuropathogenesis: in vitro and ex vivo analyses., 10th International Society for Neurovirology Conference, Milan, Italy, 1/1/10

Graduate Program Affiliations

Johns Hopkins Neuroscience Graduate Program

Memberships

  • American Association for the Advancement of Science
  • American Society for Cell Biology
  • Society for Leukocyte Biology
  • Women and Diversity Task Force

Professional Activities

  • Journal of Neuroscience, Journal peer review, 1/1/05
  • Journal of Neurovirology, Journal peer review, 1/1/10
  • Research & Reviews - A Journal of Neuroscience, Section Editor, Journal peer review, 1/1/11

Additional Training

Johns Hopkins School of Medicine, Baltimore, MD, 2004, Postdoctoral Fellow; Aaron Diamond AIDS Research Center, New York, NY, 1999, Post-doctoral Fellowship

Expertise

Education

  • Albert Einstein College of Medicine of Yeshiva University (Bronx), Ph.D., 1996
  • University of California (Riverside), B.S., 1989