Dr Alexandra Brown

Post Doctorate Researcher

School of Biomedical Sciences and Pharmacy

Career Summary

Qualifications

  • Doctor of Philosophy, University of Newcastle
  • Bachelor of Biomedical Sciences, University of Newcastle
  • Bachelor of Biomedical Sciences (Hons), University of Newcastle

Keywords

  • Immunology
  • Microbiology
  • Respiratory Disease

Languages

  • English (Mother)

Fields of Research

Code Description Percentage
110799 Immunology not elsewhere classified 30
110309 Infectious Diseases 30
110203 Respiratory Diseases 40

Professional Experience

UON Appointment

Title Organisation / Department
Post Doctorate Researcher University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Awards

Award

Year Award
2016 ICI Travel Award
Australasian Society for Immunology

Recipient

Year Award
2019 Faculty of Health and Medicine Research Travel Grant Scheme
Faculty of Health and Medicine, The University of Newcastle
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (14 outputs)

Year Citation Altmetrics Link
2020 Ali MK, Kim RY, Brown AC, Donovan C, Vanka KS, Mayall JR, et al., 'Critical role for iron accumulation in the pathogenesis of fibrotic lung disease.', J Pathol, 251 49-62 (2020)
DOI 10.1002/path.5401
Citations Scopus - 4Web of Science - 4
Co-authors Chantal Donovan, Jay Horvat, Liz Milward, Jemma Mayall, Philip Hansbro
2020 Ali MK, Kim RY, Brown AC, Mayall JR, Karim R, Pinkerton JW, et al., 'Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma.', Eur Respir J, 55 (2020)
DOI 10.1183/13993003.01340-2019
Citations Web of Science - 1
Co-authors Peter Wark, Jay Horvat, Philip Hansbro, Jemma Mayall, Malcolm Starkey, Chantal Donovan, Liz Milward, Liz Holliday, Paul Foster
2020 Marshall RJ, Armart P, Hulme KD, Chew KY, Brown AC, Hansbro PM, et al., 'Glycemic variability in diabetes increases the severity of influenza', mBio, 11 (2020)

© 2020, American Society for Microbiology. All rights reserved. People with diabetes are two times more likely to die from influenza than people with no underlying medical conditi... [more]

© 2020, American Society for Microbiology. All rights reserved. People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are un-clear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.

DOI 10.1128/mBio.02841-19
Co-authors Philip Hansbro
2019 Keenan CR, Iannarella N, Garnham AL, Brown AC, Kim RY, Horvat JC, et al., 'Polycomb repressive complex 2 is a critics mediator of allergic inflammation', JCI INSIGHT, 4 (2019) [C1]
DOI 10.1172/jci.insight.127745
Citations Scopus - 2Web of Science - 2
Co-authors Jay Horvat, Philip Hansbro
2017 Liu G, Cooley MA, Nair PM, Donovan C, Hsu AC, Jarnicki AG, et al., 'Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c', JOURNAL OF PATHOLOGY, 243 510-523 (2017) [C1]
DOI 10.1002/path.4979
Citations Scopus - 24Web of Science - 27
Co-authors Christopher Grainge, Darryl Knight, Peter Wark, Nicole Hansbro, Paul Foster, Hock Tay, Philip Hansbro, Jay Horvat, Alan Hsu, Chantal Donovan
2017 Kim RY, Pinkerton JW, Essilfie AT, Robertson AAB, Baines KJ, Brown AC, et al., 'Role for NLRP3 inflammasome-mediated, IL-1ß-dependent responses in severe, steroid-resistant asthma', American Journal of Respiratory and Critical Care Medicine, 196 283-297 (2017) [C1]

© 2017 by the American Thoracic Society. Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pat... [more]

© 2017 by the American Thoracic Society. Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1ß responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. Objectives: To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1ß in severe, steroid-resistant asthma. Methods: We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.

DOI 10.1164/rccm.201609-1830OC
Citations Scopus - 100Web of Science - 97
Co-authors Lisa Wood, Jay Horvat, Darryl Knight, Jemma Mayall, Philip Hansbro, Peter Gibson, Peter Wark, Malcolm Starkey, Katherine Baines, Jodie Simpson, Nicole Hansbro
2016 Simpson JL, Baines KJ, Horvat JC, Essilfie AT, Brown AC, Tooze M, et al., 'COPD is characterized by increased detection of Haemophilus influenzae, Streptococcus pneumoniae and a deficiency of Bacillus species', Respirology, 21 697-704 (2016) [C1]

© 2016 Asian Pacific Society of Respirology. Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammat... [more]

© 2016 Asian Pacific Society of Respirology. Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammation. Airway bacterial colonization is increased in COPD; however, the role of potentially pathogenic and non-pathogenic bacteria in the pathogenesis of disease is unclear. This study characterized the presence of bacteria in a well-characterized cohort of adults with COPD and healthy controls. Methods Adults with COPD (n = 70) and healthy controls (n = 51) underwent clinical assessment and sputum induction. Sputum was dispersed, and total and differential cell counts were performed. Bacteria were cultured, identified and enumerated. Supernatants were assessed for neutrophil elastase (NE) and IL-1ß. Common respiratory pathogens were also determined using real-time PCR. Results Participants with COPD had a typical neutrophilic inflammatory profile. The total load of bacteria was increased in COPD and was associated with poorer respiratory health status, as measured by the St George's Respiratory Questionnaire (Spearman's r = 0.336, P = 0.013). Significantly lower levels of culturable Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1ß, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.

DOI 10.1111/resp.12734
Citations Scopus - 28Web of Science - 27
Co-authors Katherine Baines, Jay Horvat, Vanessa Mcdonald, Philip Hansbro, Jodie Simpson, Peter Gibson
2016 Gold MJ, Hiebert PR, Park HY, Stefanowicz D, Le A, Starkey MR, et al., 'Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization', Mucosal Immunology, 9 809-820 (2016) [C1]

Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contrib... [more]

Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM 10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM 10 -induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.

DOI 10.1038/mi.2015.104
Citations Scopus - 30Web of Science - 32
Co-authors Malcolm Starkey, Philip Hansbro, Jay Horvat, Darryl Knight
2016 Starkey MR, Nguyen DH, Brown AC, Essilfie AT, Kim RY, Yagita H, et al., 'PD-L1 Promotes Early-life Chlamydia Respiratory Infection-induced Severe Allergic Airway Disease.', American journal of respiratory cell and molecular biology, (2016) [C1]
Citations Scopus - 12Web of Science - 13
Co-authors Philip Hansbro, Jay Horvat, Malcolm Starkey
2013 Starkey MR, Nguyen DH, Kim RY, Nair PM, Brown AC, Essifie A-T, et al., 'Programming of the Lung in Early Life by Bacterial Infections Predisposes to Chronic Respiratory Disease', CLINICAL OBSTETRICS AND GYNECOLOGY, 56 566-576 (2013) [C1]
DOI 10.1097/GRF.0b013e3182993a0c
Citations Scopus - 12Web of Science - 11
Co-authors Malcolm Starkey, Jay Horvat, Philip Hansbro
2013 Thorburn AN, Brown AC, Nair PM, Chevalier N, Foster PS, Gibson PG, Hansbro PM, 'Pneumococcal Components Induce Regulatory T Cells That Attenuate the Development of Allergic Airways Disease by Deviating and Suppressing the Immune Response to Allergen', JOURNAL OF IMMUNOLOGY, 191 4112-4120 (2013) [C1]
DOI 10.4049/jimmunol.1201232
Citations Scopus - 15Web of Science - 14
Co-authors Philip Hansbro, Peter Gibson, Paul Foster
2013 Starkey MR, Jarnicki AG, Essilfie A-T, Gellatly SL, Kim RY, Brown AC, et al., 'Murine models of infectious exacerbations of airway inflammation', CURRENT OPINION IN PHARMACOLOGY, 13 337-344 (2013) [C1]
DOI 10.1016/j.coph.2013.03.005
Citations Scopus - 43Web of Science - 44
Co-authors Jay Horvat, Malcolm Starkey, Philip Hansbro, Paul Foster
2012 Brown A, 'Preventing venous thromboembolism in hospitalized patients with cancer: Improving compliance with clinical practice guidelines', American Journal of Health-System Pharmacy, 69 469-481 (2012)

Purpose. The use of anticoagulants for the prevention of venous thromboembolism (VTE) in hospitalized medical and surgical oncology patients is discussed. Summary. Hospitalized pa... [more]

Purpose. The use of anticoagulants for the prevention of venous thromboembolism (VTE) in hospitalized medical and surgical oncology patients is discussed. Summary. Hospitalized patients are often at risk for developing VTE, and risk is increased in patients who have cancer. Moreover, the incidence of VTE appears to be rising in hospitalized cancer patients, who have a 2.2-fold increased risk of mortality with a VTE compared with similar patients without VTE. The literature indicates that these patients are often inadequately anticoagulated, despite strong recommendations for prophylaxis. Although there are few studies that specifically address VTE prophylaxis in cancer patients, there are several large trials that have examined data in cancer subgroups. The trials have directly compared low-molecular-weight heparin (LMWH) with placebo, unfractionated heparin with LMWH, factor Xa inhibitor (fondaparinux) with placebo, and fondaparinux with LMWH. Three important guidelines provide current recommendations for VTE prophylaxis; the American Society of Clinical Oncology (ASCO), theNational Comprehensive Cancer Network (NCCN), and the American College of Chest Physicians (ACCP) recommend unfractionated heparin, LMWH, or fondaparinux for VTE prophylaxis when there are no contraindications. Pharmacists can play an essential role in ensuring that VTE prophylaxis is appropriate for individual patients. Interventions to improve compliance with guidelines are particularly important now due to financial incentives from qualityfocused organizations whose mandate is to decrease preventable mortality events in hospitals. Conclusion. Hospitalized patients with cancer often do not receive appropriate thromboprophylaxis. Guidelines from ASCO, ACCP, and NCCN recommend unfractionated heparin, an LMWH, or fondaparinux for VTE prophylaxis when there are no contraindications to such therapy. Copyright © 2012, American Society of Health-System Pharmacists, Inc. All rights reserved.

DOI 10.2146/ajhp110187
Citations Scopus - 13
2000 Turner CJ, Parfrey P, Ryan K, Miller R, Brown A, 'Community pharmacist outreach program directed at physicians treating congestive heart failure', American Journal of Health-System Pharmacy, 57 747-752 (2000)

The predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for congestive heart failure (CHF), the use of angiotensin-converting-enzyme ... [more]

The predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for congestive heart failure (CHF), the use of angiotensin-converting-enzyme (ACE) inhibitors in this population, and the ability of a pharmacist outreach program to address underutilization of ACE inhibitors were studied. All physicians and owner-managers of community pharmacies of Newfoundland's Avalon Peninsula were asked to participate in the study. Pharmacists who agreed to participate were asked to list patients of the participating physicians with prescriptions for (1) furosemide and digoxin with and without an ACE inhibitor or angiotensin II-receptor inhibitor and (2) an ACE inhibitor. Physicians were visited by a pharmacist and asked whether each of their patients receiving digoxin and furosemide was being treated for CHF and to identify further cases of CHF among their patients receiving an ACE inhibitor. Intervention group physicians received academic detailing on the use and dosage of ACE inhibitors and angiotensin II-receptor inhibitors for CHF. Both groups were reinterviewed after three months to establish what if any changes in therapy had occurred for each patient discussed during the first visit. The positive predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for CHF was 94%. Seventy-six percent of patients identified by physicians as CHF patients who were taking digoxin and furosemide were treated with an ACE inhibitor. Thirty-six percent of patients treated with an ACE inhibitor for CHF received the targeted dosage. Four physicians stated that the outreach visit their prescribing, but there was no significant difference in ACE inhibitor prescribing between the intervention and control groups. A pharmacist outreach program involving the use of prescription records and academic detailing did not affect prescribing or dosages of ACE inhibitors but demonstrated value as a quality assurance tool.

DOI 10.1093/ajhp/57.8.747
Citations Scopus - 10
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Grants and Funding

Summary

Number of grants 3
Total funding $63,723

Click on a grant title below to expand the full details for that specific grant.


20201 grants / $12,162

Investigating the role of sex hormones in in obese and non-obese asthmatic females$12,162

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Doctor Evan Williams, Doctor Alexandra Brown, Professor Lisa Wood, Associate Professor Jay Horvat, Doctor David Arnold, Doctor Bronwyn Berthon
Scheme Research Grant
Role Investigator
Funding Start 2020
Funding Finish 2020
GNo G2000392
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y

20191 grants / $25,000

The role and therapeutic manipulation of female sex hormones in asthma$25,000

Funding body: Priority Research Centre (PRC) for Healthy Lungs | The University of Newcastle

Funding body Priority Research Centre (PRC) for Healthy Lungs | The University of Newcastle
Project Team

Alexandra Brown, Jemma Mayall, Hayley Scott, Katie Wynne, Jay Horvat, Lisa Wood

Scheme Integration Grant
Role Lead
Funding Start 2019
Funding Finish 2019
GNo
Type Of Funding Internal
Category INTE
UON N

20121 grants / $26,561

Mechanisms of predisposition to secondary bacterial pneumonia$26,561

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Alexandra Brown
Scheme Research Higher Degree Support Grant
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1201160
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y
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Research Supervision

Number of supervisions

Completed0
Current2

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2020 PhD The role & therapeutic manipulation of female sex hormones in asthma PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2016 PhD Mechanisms and Therapeutic Targeting of Immunometabolism in Lung Disease PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
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Dr Alexandra Brown

Position

Post Doctorate Researcher
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email alexandra.brown@newcastle.edu.au
Phone (02) 4042 0201

Office

Room Level 2 East
Building HMRI
Location New Lambton Heights

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