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Amanda M. Brown

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Amanda M. Brown
Brown speaks at the National Institute of Neurological Disorders and Stroke in 2018
NationalityAmerican
Alma materUniversity of California, Riverside
Albert Einstein College of Medicine
Aaron Diamond AIDS Research Center
Known forFirst cloning of recombinant HIV virus with GFP tag
Awards2018 Johns Hopkins University School of Medicine Living the Hopkins Mission Honor, 2014 Keystone Symposia on Molecular and Cell Biology Fellow, 2014 Johns Hopkins Diversity Leadership Award
Scientific career
FieldsNeuroimmunology
InstitutionsJohns Hopkins University School of Medicine

Amanda Brown is an American immunologist and microbiologist as well as an associate professor of neurology and neuroscience at Johns Hopkins University School of Medicine in Baltimore, Maryland. Brown is notable for cloning one of the first recombinant HIV viruses[1] and developing a novel method to visualize HIV infected cells using GFP fluorescence.

As a principal investigator at Johns Hopkins, Brown studies HIV in the central nervous system, focusing on the cellular role of osteopontin in regulating inflammatory signalling pathways in HIV infected macrophages. Brown also explores how microglia and macrophages serve as latent viral reservoirs in order to target these mechanisms to prevent HIV-associated neurocognitive disorder. In addition to her research, Brown mentors and recruits the future cohort of diverse leaders in STEM, serving as director of the Johns Hopkins Neuroscience Scholars Program, and for 10 years serving as program director for the Department of Neurology Johns Hopkins Internship in Brain Sciences Program for Baltimore City High School Students.

Early life and education

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Brown pursued her undergraduate degree at the University of California, Riverside in 1985.[2] She majored in Biochemistry and graduated with a Bachelor of Science in 1989.[2] After her undergraduate degree, Brown began her graduate studies at Albert Einstein College of Medicine, where she completed her PhD in microbiology and immunology.[3] She studied under the mentorship of William R. Jacobs.[2] During her PhD, she became interested in macrophage-pathogen biology and was selected to take a Cold Spring Harbor Course on Advanced Bacterial Genetics.[4]

Brown helped to develop a novel method to study the mechanisms underlying mycobacterium replication in mononuclear phagocytes.[5] Brown and her colleagues developed a leucine auxotrophic mutant that the field could use to study the host-pathogen interactions of mycobacterium and the animal cells thy replicate in.[5] Brown also explored the sec-dependent protein export pathway in mycobacterium, the main protein export pathway into the cytoplasm, and discovered the presence of two homologues of the SecA protein.[6] SecA1 they found to be essential, but SecA2 they found to be nonessential but conserved across mycobacteria suggesting its alternate and unknown roles in pathogenesis and mycobacterium physiology.[6]

Development of recombinant HIV reporter tool

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Brown completed her PhD in 1996, and continued to study intracellular pathogens that are able to evade the immune response.[2] Brown pursued her postdoctoral training at the Aaron Diamond AIDS Research Center in New York City, where she studied under the mentorship of Cecilia Cheng-Meyer.[3] During her postdoctoral studies Brown led the cloning of the first recombinant HIV virus that enabled the visualization of HIV infected cells by expressing green fluorescent protein.[1] She later used this technology to explore the role of HIV protein Nef in pathogenesis, finding that Nef's interaction with cellular kinases enables the removal of CD4 from the surface of infected macrophages.[7] Brown also used this fluorescent tool to discover that HLA-A2 is down-regulated in HIV infected macrophages.[8] Further, Brown was the first to model the HIV-macrophage reservoir using her fluorescent tagging tool, and this method continues to be used today to study latent HIV infection.[9]

From 1999 to 2003, Brown completed a second postdoctoral fellowship at Johns Hopkins University School of Medicine in Baltimore, Maryland.[2] She worked under Suzanne Gartner in the Department of Neurology studying HIV infection in macrophages, with a focus on the infection of macrophages in the brain, namely microglia.[9]

Career and research

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In 2007, Brown became an instructor in the Department of Neurology, and in 2010 Brown was appointed to the faculty at Johns Hopkins University School of Medicine, where she became an assistant professor of neurology in the Department of Neurology.[4] In 2016, Brown was promoted to associate professor in the Department of Neurology.[10] As the principal investigator of the Brown Laboratory Research Group, Brown explores how HIV infection persists in macrophages and how the chronic inflammatory response, as a result of infection, leads to neuronal damage and neurodegeneration.[10]

Academic leadership

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In addition to her research, Brown has held many leadership positions at Johns Hopkins School of Medicine. In 2015, Brown established the Neurosciences Community Innovation Council and became vice chair of the department.[11] Brown is also the co-director of the Developmental Core for the NIMH Johns Hopkins Center for Novel Therapeutics for HIV-Associated Cognitive Disorders.[12] During the COVID-19 pandemic, Brown was elected a member of the Johns Hopkins University School of Medicine Pandemic Academic Advisory Committee.[13]

Education and outreach leadership

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Brown also serves as a director of the Hopkins NeuroHIV-Comorbidities Scholars program[14] and also Directs the Translational Research in Neuro-AIDS and Mental Health program at Johns Hopkins School of Medicine.[15] Brown secured an R25 grant from the National Institutes of Health to run this program which educates research across the United States and internationally about the effects of HIV infection in racial and ethnic minority populations.[16]

Brown was also the director of the Johns Hopkins Internship in Brain Sciences (JHIBS) Program, also supported by the NIH R25 grant that Brown obtained.[17] The JHIBS program recruits underrepresented minority high school students in the Baltimore area to experience research as a paid intern for 8 weeks at JHSOM.[18] Over 150 high school students have participated in the program throughout Brown's leadership tenure and the students have an 84% matriculation rate into college.[11]

Brown, with the help of Tilak Ratnanather, founded the Johns Hopkins Neuroscience Scholars Program which helps to recruit and retain underrepresented minority students in neuroscience and is funded by the National Institutes of Neurological Disorders and Stroke.[19] This national program focused on mentoring underrepresented and deaf or hard-of-hearing undergraduates to obtain career development and research exposure in neuroscience.[20]

Osteopontin signalling in HIV infection of the central nervous system

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Brown focuses her research program on studying the role of osteopontin in HIV pathogenesis in the central nervous system. Osteopontin is a pro-inflammatory cytokine that is secreted by the two main cells in the brain that HIV infects, namely T cells and macrophages.[21] Brown found, in 2011, that osteopontin enhances HIV replication and is overall increased in the brains of HIV infected individuals.[22] Further exploring its mechanisms of action, Brown discovered in 2020 that osteopontin may exert protective functions in the CNS through interacting with components of the extracellular matrix to active downstream protective signalling.[23]

Awards and honors

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References

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  1. ^ a b Brown, Amanda M. (2009). "Use of a Macrophage-Tropic GFP-Tagged Human Immunodeficiency Virus Type 1 (HIV-1) to Study Viral Reservoirs". Viral Applications of Green Fluorescent Protein. Methods in Molecular Biology. Vol. 515. pp. 165–175. doi:10.1007/978-1-59745-559-6_11. ISBN 978-1-934115-87-9. ISSN 1064-3745. PMID 19378134.
  2. ^ a b c d e "Amanda M. Brown, Ph.D., Associate Professor of Neurology". Johns Hopkins Medicine. Retrieved 2020-06-28.
  3. ^ a b "Meet the W&D Committee". leukocytebiology.org. Archived from the original on 2019-12-29. Retrieved 2020-06-28.
  4. ^ a b "On Fire: HIV in the Brain- Taming the Flame". ninds.nih.gov. 2019. Archived from the original on 2019-04-10. Retrieved June 27, 2020.
  5. ^ a b Bange, Franz Christoph; Brown, Amanda M.; Jacobs, William R. (1996-01-01). "Leucine auxotrophy restricts growth of Mycobacterium bovis BCG in macrophages". Infection and Immunity. 64 (5): 1794–1799. doi:10.1128/iai.64.5.1794-1799.1996. ISSN 0019-9567. PMC 173994. PMID 8613393.
  6. ^ a b Braunstein, M.; Brown, A. M.; Kurtz, S.; Jacobs, W. R. (December 2001). "Two nonredundant SecA homologues function in mycobacteria". Journal of Bacteriology. 183 (24): 6979–6990. doi:10.1128/JB.183.24.6979-6990.2001. ISSN 0021-9193. PMC 95544. PMID 11717254.
  7. ^ Brown, Amanda; Moghaddam, Shaghayegh; Kawano, Thomas; Cheng-Mayer, Cecilia (June 2004). "Multiple human immunodeficiency virus type 1 Nef functions contribute to efficient replication in primary human macrophages". The Journal of General Virology. 85 (Pt 6): 1463–1469. doi:10.1099/vir.0.79946-0. ISSN 0022-1317. PMID 15166429.
  8. ^ Brown, Amanda; Gartner, Suzanne; Kawano, Thomas; Benoit, Nicole; Cheng-Mayer, Cecilia (September 2005). "HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus". Journal of Leukocyte Biology. 78 (3): 675–685. doi:10.1189/jlb.0505237. ISSN 0741-5400. PMID 16000390.
  9. ^ a b Brown, Amanda; Zhang, Hao; Lopez, Peter; Pardo, Carlos A.; Gartner, Suzanne (November 2006). "In vitro modeling of the HIV-macrophage reservoir". Journal of Leukocyte Biology. 80 (5): 1127–1135. doi:10.1189/jlb.0206126. ISSN 0741-5400. PMID 16923921. S2CID 14355067.
  10. ^ a b c d "About | Best Neuroscience Program | JHNSP". Johns Hopkins Neuroscience Scholars Program. Retrieved 2020-06-28.
  11. ^ a b c "Living the Hopkins Mission Honorees". www.hopkinsmedicine.org. Retrieved 2020-06-28.
  12. ^ "Development Core | Johns Hopkins NIMH Center". www.hopkinsmedicine.org. Retrieved 2020-06-28.
  13. ^ "University Pandemic Academic Advisory Committee". The Hub. Retrieved 2020-06-28.
  14. ^ "Amanda Brown". neuroscience.jhu.edu. Retrieved 2020-06-28.
  15. ^ "Translational Research in Neuro-AIDS and Mental Health" (PDF). cfar.globalhealth.harvard.edu. 2014. Retrieved June 27, 2020.
  16. ^ Brown, Amanda. "The Johns Hopkins NeuroHIV Comorbidities Scholar Program". {{cite journal}}: Cite journal requires |journal= (help)
  17. ^ "Past Intern Research Projects | Johns Hopkins Internship in Brain Sciences". www.hopkinsmedicine.org. Retrieved 2020-06-28.
  18. ^ "Overview". Johns Hopkins Internship in Brain Sciences. 2015-06-15. Retrieved 2020-06-28.
  19. ^ "Charles Wiener named president of Johns Hopkins Medicine International". The Hub. 2018-12-20. Retrieved 2020-06-28.
  20. ^ "Johns Hopkins Neuroscience Scholars Program". www.pathwaystoscience.org. Retrieved 2020-06-28.
  21. ^ Brown, Amanda (2012-02-01). "Osteopontin: A key link between immunity, inflammation and the central nervous system". Translational Neuroscience. 3 (3): 288–293. doi:10.2478/s13380-012-0028-7. ISSN 2081-3856. PMC 3616337. PMID 23565338.
  22. ^ Brown, Amanda; Islam, Tanzeem; Adams, Robert; Nerle, Sujata; Kamara, Masiray; Eger, Caitlin; Marder, Karen; Cohen, Bruce; Schifitto, Giovanni; McArthur, Justin C.; Sacktor, Ned (August 2011). "Osteopontin enhances HIV replication and is increased in the brain and cerebrospinal fluid of HIV-infected individuals". Journal of Neurovirology. 17 (4): 382–392. doi:10.1007/s13365-011-0035-4. ISSN 1538-2443. PMC 3331788. PMID 21556958.
  23. ^ Mahmud, Farina J.; Boucher, Thomas; Liang, Shijun; Brown, Amanda M. (2020-06-04). "Osteopontin and Integrin Mediated Modulation of Post-Synapses in HIV Envelope Glycoprotein Exposed Hippocampal Neurons". Brain Sciences. 10 (6): 346. doi:10.3390/brainsci10060346. ISSN 2076-3425. PMC 7349055. PMID 32512754.
  24. ^ "YouTube". www.youtube.com. 16 November 2015. Retrieved 2020-06-28.
  25. ^ "Cheers". The Hub. 2014-07-01. Retrieved 2020-06-28.
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