Dr Ayesha Ayesha

Associate Lecturer

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

Dr Ayesha Ali is an Early Career Researcher and Associate Lecturer at the University of Newcastle and Hunter Medical Research Institute. Dr Ali obtained a Bachelor by Honours (2012), and a Master’s by Research (2014) in Biotechnology followed a PhD (2019) in Medical Biochemistry from the University of Newcastle. During her PhD, she worked on studying the molecular mechanisms underlying the development, homeostasis, regeneration, and diseases of the female lower reproductive tract. Specifically, she developed the patented technology of culturing lower reproductive tract organoids, now routinely used to generate organoids from patient gynecological biopsies. Her patented technology is essential for more efficient translation of basic research into novel treatment regimens for patients with disease like reproductive cancers and endometriosis. These organoids can be cryopreserved and stored in living organoid biobanks to create a shared resource for other Australian researchers to facilitate improved human disease modelling to enhance drug translation to the clinic. She is an emerging international expert in stem cell biology as highlighted by her landmark paper in Cell Reports and Cell Stem Cell.

After completing her PhD Dr Ali began work focusing on study inflammatory bowel diseases (IBD), ulcerative colitis and Crohn’s disease and Colorectal cancer. She has generated large collections of IBD patient-derived and healthy gastrointestinal organoids creating an intestinal organoid bio-bank. Dr Ali's work currently focuses on toxicology screening of human intestinal organoids with environmental compounds epidemiologically linked to gut diseases. Dr Ali now aims to combine artificial intelligence algorithms developed using IBD patient datasets with these intestinal organoids to design new and improved targeted drugs to enhance IBD mucosal healing. Dr Ali's research uses cutting edge techniques, including development of 3D organoids/spheroids, human and mouse genome editing, patient derived xenografts models, preclinical drug trials in animal models, single cell-RNA sequencing, and advanced imaging techniques.


Qualifications

  • Doctor of Philosophy in Medical Biochemistry, University of Newcastle

Keywords

  • Stem cells, Epithelial repair/regeneration, IBD

Languages

  • English (Mother)

Fields of Research

Code Description Percentage
320209 Gastroenterology and hepatology 100

Professional Experience

UON Appointment

Title Organisation / Department
Associate Lecturer University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
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Publications

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


Journal article (6 outputs)

Year Citation Altmetrics Link
2021 Wark PAB, Pathinayake PS, Kaiko G, Nichol K, Ali A, Chen L, et al., 'ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma', Respirology, 26 442-451 (2021) [C1]

Background and objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine protea... [more]

Background and objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. Methods: We obtained lower AEC from 145 people from two independent cohorts, aged 2¿89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.

DOI 10.1111/resp.14003
Citations Scopus - 13Web of Science - 10
Co-authors Nathan Bartlett, Christopher Oldmeadow, Andrew Reid, Ling Chen, Gerard Kaiko, Philip Hansbro, Prabuddha Pathinayake, Peter Wark, Alan Hsu, Punnam Veerati
2020 Ali A, Syed SM, Tanwar PS, 'Protocol for In Vitro Establishment and Long-Term Culture of Mouse Vaginal Organoids', STAR Protocols, 1 (2020)

Healthy vaginal epithelium is essential for normal reproductive functions and protects against infectious diseases. Here, we present a protocol for developing mouse vaginal organo... [more]

Healthy vaginal epithelium is essential for normal reproductive functions and protects against infectious diseases. Here, we present a protocol for developing mouse vaginal organoids from single epithelial cells. These organoids recapitulate both functional and structural characteristics of vagina in situ. This model is a powerful tool for investigating how vaginal microbiome or chemicals in contraceptives and personal hygiene products interact with stem cells and alter the epithelial dynamics, which will lead to new insights into the pathogenesis of vaginal diseases. For complete details on the use and execution of this protocol, please refer to Ali et al. (2020).

DOI 10.1016/j.xpro.2020.100088
Co-authors Shafiq Syed, Pradeep Tanwar
2020 Ali A, Syed SM, Jamaluddin MFB, Colino-Sanguino Y, Gallego-Ortega D, Tanwar PS, 'Cell Lineage Tracing Identifies Hormone-Regulated and Wnt-Responsive Vaginal Epithelial Stem Cells', Cell Reports, 30 1463-1477.e7 (2020) [C1]

The intact vaginal epithelium is essential for women's reproductive health and provides protection against HIV and sexually transmitted infections. How this epithelium mainta... [more]

The intact vaginal epithelium is essential for women's reproductive health and provides protection against HIV and sexually transmitted infections. How this epithelium maintains itself remains poorly understood. Here, we used single-cell RNA sequencing (RNA-seq) to define the diverse cell populations in the vaginal epithelium. We show that vaginal epithelial cell proliferation is limited to the basal compartment without any obvious label-retaining cells. Furthermore, we developed vaginal organoids and show that the basal cells have increased organoid forming efficiency. Importantly, Axin2 marks a self-renewing subpopulation of basal cells that gives rise to differentiated cells over time. These cells are ovariectomy-resistant stem cells as they proliferate even in the absence of hormones. Upon hormone supplementation, these cells expand and reconstitute the entire vaginal epithelium. Wnt/ß-catenin is essential for the proliferation and differentiation of vaginal stem cells. Together, these data define heterogeneity in vaginal epithelium and identify vaginal epithelial stem cells.

DOI 10.1016/j.celrep.2020.01.003
Citations Scopus - 5Web of Science - 4
Co-authors Pradeep Tanwar, Muhammad Jamaluddin, Shafiq Syed
2020 Ali A, Tan H, Kaiko GE, 'Role of the Intestinal Epithelium and Its Interaction With the Microbiota in Food Allergy', FRONTIERS IN IMMUNOLOGY, 11 (2020) [C1]
DOI 10.3389/fimmu.2020.604054
Citations Scopus - 3Web of Science - 2
Co-authors Gerard Kaiko
2020 Syed SM, Kumar M, Ghosh A, Tomasetig F, Ali A, Whan RM, et al., 'Endometrial Axin2 Cells Drive Epithelial Homeostasis, Regeneration, and Cancer following Oncogenic Transformation', Cell Stem Cell, 26 64-80.e13 (2020) [C1]
DOI 10.1016/j.stem.2019.11.012
Citations Scopus - 27Web of Science - 26
Co-authors Shafiq Syed, Pradeep Tanwar
2016 Kumar M, Atkins J, Cairns M, Ali A, Tanwar PS, 'Germ cell-specific sustained activation of Wnt signalling perturbs spermatogenesis in aged mice, Possibly through non-coding RNAs', Oncotarget, 7 85709-85727 (2016) [C1]

Dysregulated Wnt signalling is associated with human infertility and testicular cancer. However, the role of Wnt signalling in male germ cells remains poorly understood. In this s... [more]

Dysregulated Wnt signalling is associated with human infertility and testicular cancer. However, the role of Wnt signalling in male germ cells remains poorly understood. In this study, we first confirmed the activity of Wnt signalling in mouse, dog and human testes. To determine the physiological importance of the Wnt pathway, we developed a mouse model with germ cell-specific constitutive activation of ßcatenin. In young mutants, similar to controls, germ cell development was normal. However, with age, mutant testes showed defective spermatogenesis, progressive germ cell loss, and flawed meiotic entry of spermatogonial cells. Flow sorting confirmed reduced germ cell populations at the leptotene/zygotene stages of meiosis in mutant group. Using thymidine analogues-based DNA double labelling technique, we further established decline in germ cell proliferation and differentiation. Overactivation of Wnt/ßcatenin signalling in a spermatogonial cell line resulted in reduced cell proliferation, viability and colony formation. RNA sequencing analysis of testes revealed significant alterations in the non-coding regions of mutant mouse genome. One of the novel non-coding RNAs was switched on in mutant testes compared to controls. QPCR analysis confirmed upregulation of this unique noncoding RNA in mutant testis. In summary, our results highlight the significance of Wnt signalling in male germ cells.

DOI 10.18632/oncotarget.13920
Citations Scopus - 6Web of Science - 5
Co-authors Pradeep Tanwar, Murray Cairns
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Grants and Funding

Summary

Number of grants 1
Total funding $4,955

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


20211 grants / $4,955

3D printing a bioengineered gut-on-a-chip: pilot project consumables to build a 3D platform for a human gut-on-a-chip to use in disease modelling$4,955

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Ayesha Ayesha, Doctor Adam Fahy, Doctor Bojan Stojkovic
Scheme Research Grant
Role Lead
Funding Start 2021
Funding Finish 2021
GNo G2101064
Type Of Funding C3300 – Aust Philanthropy
Category 3300
UON Y
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Dr Ayesha Ayesha

Position

Associate Lecturer
Foster Group
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing

Contact Details

Email ayesha.ayesha@newcastle.edu.au
Phone (02) 40420227
Mobile 0451076623

Office

Room HMRI level-2 (East)
Building Hunter Medical Research Centre (HMRI)
Location Hunter medical Research Center

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