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Prof.Dr. Musarat Ishaq

Professor

Research Profile

Dr Musarat Ishaq was awarded his PhD in 2008 from Wuhan University, China. He did postdoctoral training at the University of Wisconsin-Madison (Madison, USA) from 2008-2010 and at Stockholm University (Stockholm, Sweden) from 2011-2012. He then worked as a Biomedical Scientist at Commonwealth Scientific and Industrial Research Organization (CSIRO, Sydney, Australia) from 2012-2015, at Peter MacCallum Cancer Centre (Melbourne, Australia) from 2015-2016, and at St Vincent Institute of Medical Research (SVI)/University of Melbourne (Melbourne, Australia) from 2017-2023. His research focus was on Human Viruses (studying the role of host cellular factors involved in the transcription and replication of SARS-corona, HIV, HCV, and Influenza), Systems Biology, and Mathematical Modeling to study virus-host interaction (oncolytic viruses, e.g., VSV), Developmental Biology (developing transgenic animals to study genes involved in metabolic disorders, e.g., obesity), Radiotherapy to treat resistant tumors e.g., melanoma and colorectal cancer, Tumor Angiogenesis (studying role of lymphatic and blood vessels for tumor growth and metastasis) & Metabolic and Fat-disorders (role of adipose tissue in metabolic disorders e.g., obesity, diabetes). He has published over 30 peer-reviewed research articles and presented his work at several international conferences. Dr Ishaq is a member of several professional scientific organizations, including Lipedema World Alliance, Italy, the Australian & New Zealand (ANZOS) Obesity Society, the Australian Society for Microbiology & International Society for Systems Biology.

EDUCATION/TRAINING:

INSTITUTION AND LOCATION

DEGREE/TRAINING

START DATE

 

END DATE

FIELD OF STUDY/

RESEARCH

University of Agricultural Faisalabad, Pakistan

DVM

07/1997

11/2001

Doctor of Veterinary Medicine

University of Veterinary and Animal Sciences Lahore, Pakistan

MSC

02/2002

03/2004

Microbiology

Clinical/Research Training

House Job

04/2004

05/2005

Veterinary Research Centre, Okara/Veterinary Research Institute, Lahore

Wuhan University, China

PhD

06/2005

10/2008

Microbiology & Molecular Biology

University of Wisconsin-Madison, USA

Postdoc Fellow

11/2008

02/2011

Systems Biology & Immunology

University of Lahore, Pakistan

Assistant Professor

03/2011

06/2011

Molecular Biology and Biotechnology

Stockholm University, Sweden

Postdoc Fellow

07/2011

02/2012

Developmental Biology

Commonwealth Scientific & Industrial Research Organisation (CSIRO), Sydney, Australia

Scientist

03/2012

03/2015

Cancer Biology/Plasma Physics/Nanomedicine

Peter MacCallum Cancer Centre, Melbourne, Australia

Scientist

04/2015

06/2016

Tumor Angiogenesis

St Vincent Institute of Medical Research, Melbourne/University of Melbourne, Australia

Senior Scientist

09/2016

12/2023

Metabolic & Fat Disorders/Regenerative Medicine

MRB NextGenTech Pty Ltd, Melbourne, Australia

Senior Consultant

01/2017

Present

Biotech Research& Development/Molecular Diagnostics Lab Development/Biomedical Research Training

Personal Statement

My academic training and research experience have provided me with an excellent background in multidisciplinary biomedical and engineering fields, including microbiology (human viruses & oncolytic viruses), immunology (host-pathogen interaction), systems biology (single-cell sequencing, transcriptomics, proteomics, genomics, metabolomics, lipidomics, microRNA-seq, ChiP-seq, DNA-sequencing & bioinformatics skills), developmental biology (recombinant-DNA technology, epigenetics & transgenic animals), cancer cell biology (tumor angiogenesis and development of anti-cancer treatments), obesity and adipose tissue-associated metabolic disorders, stem cells biology, regenerative medicine, nano-materials, plasma physic and radiations biology (radiotherapy). I conducted PhD research at Wuhan University, China, on the mechanisms of RNA helicases for HIV transcription and replication. As a postdoctoral fellow at the University of Wisconsin-Madiosn, USA, I established in-vitro immune deficient/intact cell culture models to understand virus-host interaction using systems biology approaches and mathematical modeling. During my postdoctoral training at Stockholm University, Sweden, I established transgenic animals (Drosophila) to understand the role of transcription factors (breakless & atropine) involved in diabetes during the early stages of development. This experience allowed me to learn recombinant DNA technology and its application to animal models.  I joined CSIRO, Australia, to test atmospheric gas plasma-generated radiations (reactive oxygen/nitrogen species) for cancer treatment. I developed the protocol for treating drug-resistance tumors using atmospheric plasma-generated reactive species (H2O2, OH, O3). I worked at Peter MacCallum Cancer Centre, Australia, to discover the role of microRNAs in VEGF-induced tumor angiogenesis. I found one microRNA132 which induces cancer cell proliferation by regulating VEGF-C/D secretion. At St Vincent Institute of Medical Research/University of Melbourne, Australia, I used systems biology approaches, omics technology, and computational tools to find new targets that can be used to develop diagnostic tests and treatments for metabolic & fat disorders, including obesity, diabetes, and lipedema. During my graduate and research training careers, I received several academic awards. I have published more than 25 peer-reviewed research papers. I have presented my research at more than 15 international conferences. I am an associate editor and reviewer for more than five peer-reviewed journals. I have taught several advanced courses in the biomedical field for graduate students.

Positions and Scientific Appointments

2022-present             Committee member, Lipedema World Alliance, Italy

2021-present             Research fellow, University of Melbourne

2012-present             Member, Australian Society for Microbiology

2012-present             Member, International Society for Systems Biology

2012 – 2013               Research trainee, University of Greifswald, Germany

2010 – 2011               Assistant Professor, University of Lahore, Pakistan

2009 – 2016               Member, American Society for Cancer Research

2005 – 2008               Teaching assistant, Wuhan University, China

2004 – 2005               House job training, Veterinary Research Institute Lahore, Pakistan

2002 – 2003               Research Assistant, University of Veterinary Sciences Lahore, Pakistan

Honors & Awards

2008                          Wuhan University Best Graduate Student and Young Researcher Award

2011 – 2012               Research Fellowship, UW-Madison USA – Swedish Ministry of Science

2012 – 2015               OCE Fellowship, CSIRO Australia

2016-2023                Lipedema Foundation Australia, Research Grant Fellowship

 

Teaching Experience:
  • Molecular Biology
  • Human Virology
  • Immunology
  • Genomics & Systems Biology
  • Regenerative Medicine and Stem Cell Biology
  • Metabolic Diseases
  • Adipose Tissue Biology
  • Nanomaterial, Healthcare, and Medicine
Journals Reviewer 
  • Frontiers in Cell and Developmental Biology
  • International Journal of Cancer
  • Molecular Biology of the Cell
  • BBA-Bioinformatics   
  • Plasma Processes and Polymers

 

Collaborations
  • Baker Heart & Diabetes Institute (A/Prof David Greening)
  • Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus (A/Prof. Darren Creek)
  • Epigenetics and Development Department, WEHI (A/Prof. Matthew Ritchie)
  • Department of Physiology, University of Melbourne (Prof. Matthew Watt)
  • Diamantia Institute, Faculty of Medicine, The University of Queensland (Dr. Ahmad Mahdi)
  • Bioinformatics, St. Vincent’s Institute of Medical Research (Dr. Davis McCarthy)
  • Department of Dermatology, University of Wisconsin-Madison, USA (Prof. Hasan Mukhtar)
  • Department of Biomedical Sciences, Nihon University School of Medicine, Japan (Prof. Yoshihiro Suzuki-Kawasaki)

 

Conferences  
  1. Musarat Ishaq, “Virus-Host Interaction and System Biology” American Society for Virology (ASV), 29th annual meeting, Montana State University Bozeman, Montana, USA, July 2010. 
  2. Musarat Ishaq, “Cancer treatment by Oncolytic Vesicular Stomatitis Virus, a candidate anti-cancer therapeutic, System Biology approach to predict models for host-pathogen interaction” The European Conference of Oncology (ECOP), Budapest Hungary, Sep 2012.
  3. Musarat Ishaq “System Biology approach for exploring mechanism for atmospheric plasma selective tumor suppression” European Cancer Congress (ECC2013), Berlin Germany, March 2013.
  4. Musarat Ishaq, Atmospheric gas plasma kills resistant melanoma tumors without affecting normal cells, 4th International Nanomedicine Conference, Sydney, Australia, July 2013.
  5. Musarat Ishaq “Atmospheric pressure plasma as an anti-cancer therapeutic” Leibniz-Institute for Plasma Science and Technology (INP), Greifswald, Germany, Nov 2015.
  6. Musarat Ishaq, “Atmospheric plasma as a future anti-cancer therapy for malignant melanoma: steps towards pre-clinical study—12th Asia-Pacific Conference on Plasma Science and Technology, Adelaide SA, Australia, September 2016.
  7. Musarat Ishaq, Double-edged sword: ROS as a source of protection against tumor development for normal cells and as a killer for tumor cells. American Society for Cell Biology (ASCB) 2018 Annual meeting, 6-10 Dec 2018, Philadelphia, PA, USA.
  8. Musarat Ishaq, Systems Biology in anti-cancer therapies. International Workshop for Cancer Treatment 2019 March 2019, Nagoya, Japan.

Musarat Ishaq, Adipose tissue associated disorders – systems biology as a tool to discover new knowledge. Obesity and Metabolic Diseases (virtual) June 28-29, 2022, Amsterdam, Netherlands.

Research & Publications

    1. Musarat Ishaq and March Achen (2024) Lipoedema adipose-tissue: single-cell sequencing and systems biology approaches to understand disease development (invited review article is under review for IJMS, Biochemistry & Molecular Biology)
    2. S Morgan, I Reid, C Bendon, M Ishaq et al (2024) A Family-based study of inherited genetic risk in lipedema. Lymphatic Research and Biology 22 (2): 1089-95.
    3. Nureen Zahra, Basit Zeshan and Musarat Ishaq (2022) Carbapenem resistance gene crisis in A. baumannii: A computational analysis. BMC Microbiol. 2022 Dec 3;22(1):1-17.
    4. Musarat Ishaq et al (2022) Key signaling networks are dysregulated in patients with the adipose tissue disorder lipedema. Nature Int J Obes. 46(3):502-514.
    5. Arcucci V, Ishaq Musarat, et al (2021) The microRNA miR-132 is a key regulator of lymphatic vascular remodelling. bioRxiv, 2021.12.22.473780.
    6. Nureen Zahra, Basit Zeshan. M Mubeen Ali, Musarat Ishaq, et al., (2021) Phenotypic and genotypic evaluation of antibiotic resistance of Acinetobacter baumannii bacteria isolated from surgical ICU patients in Pakistan. J Microbiol; 14(4):e113008.
    7. Rubbiya A Ali, Ali Naqi, Sarah Ali, Mashal Fatima, Musarat Ishaq and Ahmad M Mehdi (2019) Statistical and Probabilistic approaches to predict protein abundance. Encyclopedia of Bioinformatics and Computational Biology, Elsevier,1(3),847-854.
    8. N Davydova, NC Harris, S Roufail, S Paquet, Musarat Ishaq, et al (2016) Differential receptor binding and regulatory mechanisms for the lymphangiogenic growth factors vascular endothelial growth factors (VEGF)-C and -D. Journal of Biological Chemistry 291 (53), 27265-27278.
    9. N Xiang, Musarat Ishaq et al (2016) The DEAD-box RNA helicase DDX3 interacts with NF-kB subunit p65 and suppresses p65-mediated transcription. PloS One 11 (10) e0164471.
    10. Musarat Ishaq et al., (2016) Effect of atmospheric plasmas on drug-resistant melanoma: the challenge of translating in vitro outcomes into animal models. Plasmas Medicine Journal DOI: 10.1615/PlasmaMed.2016015867.
    11. Musarat Ishaq et al (2015) Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells. Phys. Plasmas 22 (12), 122003.
    12. Musarat Ishaq et al (2015) Pro-apoptotic NOXA is implicated in atmospheric-pressure plasma induced melanoma cell death. Journal of Physics D: Applied Physics, 48 (46), 245-250.
    13. Musarat Ishaq et al (2015) Atmospheric pressure gas plasmas and TRAIL induce apoptosis in TRAIL-resistant colorectal cancer cells through death receptor 5 and ROS mediated signaling pathway. Plasma Process & Polymer 12(6) 572-582
    14. Musarat Ishaq et al. (2014) Atmospheric-pressure gas plasma–induced colorectal cancer cell death mediated by Nox2-ASK1 apoptosis pathways and oxidative stress mitigated by Srx-Nrf2 antioxidant system. BBA: Molecular Cell Research; 1843 (2014) 2827-2837.
    15. Fabricio Borghi, Tim Van der Laan, Musarat Ishaq, Shailesh Kumar, Kostya Ostrikov (2014) Toxicity study of water transferred graphene-based nanostructures for cell culture substrate. Plasma Physics 14(10):PO7.012.
    16. Musarat Ishaq et al. (2014) Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis. Molecular Biology of the Cell; 25 (1): 1523-1531.
    17. Musarat Ishaq et al. (2013) Effects of atmospheric gas plasmas on cancer cell signaling. International Journal of Cancer; 134 (7): 1517-1528
    18. Xiong, S. Zhao, X. Mao, X. Lu, G. He, G. Yang, M. Chen, Musarat Ishaq, K Ostrikov (2014) Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation. Stem Cell Research 12 (2), 387-399.
    19. Zhao Jun Han, Amanda Rider, Musarat Ishaq, Shailesh Kumar, Alexey Kondyurin, Marcela M. M. Bilek, Igor Levchenko and Kostya (Ken) Ostrikov, (2013) Carbon nanostructures for hard tissue engineering. RSC Advances, (3), 11058.
    20. Yongxin Mu, Yi Yu, Xin Yue, Musarat Ishaq et al, (2011) The X protein of HBV induces HIV-1 long terminal repeat transcription by enhancing the binding of C/EBPβ and CREB1/2 regulatory proteins to the long terminal repeat of HIV-1. Virus Res. 156(1-2), 81-90.
    21. Hu Tao, Chen Ping, Fu Qiong, Musarat Ishaq et al, (2010) Comparative studies of various artificial microRNA expression vectors for RNAi in mammalian cells. Mol Biotechnol 46(1), 34-40 (2010).
    22. Xiaoyun WU, Guozhen GAO, Musarat Ishaq, et al. (2010) M2 pyruvate kinase enhances HIV-1 transcription from its long terminal repeat Jour. Front. Biol. 5(1): 59-66.
    23. Junwei Li, Musarat Ishaq, Mabiala Prudence et al, (2009) Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2. Virus Res. 144(1-2), 123-9.
    24. Musarat Ishaq, Ma Li, et al, (2009) The DEAD-box RNA helicase DDX1 interacts with NF-kB subunit RelA/p65 and enhances NF-kB mediated transcription. J Cell Biochem. 1;106(2),296-305.
    25. Ji’An Pan, Xiaoxue Peng, Yajing Gao, Zhilin Li, Xiaolu Lu, Yingzhao Chen, Musarat Ishaq, et al (2008) Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARSCoV replication. PLoS ONE 10(3), e3299.
    26. Xiaoyun Wu, Musarat Ishaq, et al, (2008) HCV NS3/4A protein activates HIV-1 transcription from its long terminal repeat 1. Virus Res. 135(1), 155-160.
    27. Musarat Ishaq et al, (2008) Knockdown of cellular RNA helicase DDX3 by short hairpin RNAs suppresses HIV-1 viral replication without inducing apoptosis. Mol Biotechnol. 39(3),231-238.

      http://scholar.google.com.au/citations?user=avDxzDQAAAAJ&hl=en

    Research Projects and Support
    2016 – 2023 Supported by Lipedema Foundation Australia

    Project description: Lipedema (LED) is a debilitating disease caused by excessive fat accumulation in arms and lower extremities, affecting women at puberty. There is no known cure or diagnostic test. I conducted a genetic screening of LED-affected patients and their families and identified several gene mutations that might cause disease onset. Using omics technologies (single-cell RNA-seq, RNA-seq, proteomics, metabolomic, lipidomic) and bioinformatics tools, I identified several differentially expressed genes/proteins/metabolites (used lipedema and non-lipedema lean, obese & diabetic patients’ adipose tissues, adipocytes, and adipose-derived stem cells) involved in cell cycle/proliferation, cell adhesion/extracellular matrix and lipid metabolism which may also be involved in triggering LED, Obesity and Diabetes development. In addition, my single-cell sequencing analysis of LED tissue cell isolates (stromal vascular fraction) has identified several new sub-cellular populations and gene signatures absent in non-lipedema patients’ tissues. This project identified biomarkers that can lead to the development of the “Lipedema Molecular Diagnostic Test.” We also developed ADSCs-driven fat tissue animal models to test LED-specific drug targets. The project brought over $600,000 in external funding from Lipedema Society Australia and other donors.

    2015 – 2016   Supported by NHMRC Research Grant

    Project description: The project explored the new microRNAs/intracellular factors involved in tumor angiogenesis and metastasis regulated by vascular endothelial growth factors (VEGFs) mediated signaling pathways using the system’s biology approaches. I have used the next-generation sequencing (NGS) method to sequence all small RNAs and bioinformatics tools to find new microRNAs and their intracellular targets involved in tumor angiogenesis & metastasis, which can be potentially used as anti-cancer therapeutics. I found several microRNAs differentially up/down-regulated by VEGFs-A, C & D in lymphatics endothelial cells (LECs). I used in-vitro functional assays (gene promoter-reporter assay, proliferation assay, migration assay, and tube formation assay) by using microRNA inhibitors/mimics in LECs induced by VEGFs-A or C or D with/without VEGF-receptors R2/R3 neutralizing antibodies. I also validated the functional role of these microRNAs in in-vivo metastatic tumor animal models.

    2012 – 2015     Supported by CSIRO OCE-POSTDOCTORAL FELLOWSHIP & CSIRO CAPEX PLASMA GRANT

    Project description: The project aimed to explore the mechanisms of how atmospheric-pressure gas plasma (AGP) as a source of reactive oxygen species (ROS) induces apoptosis (programmed cell death) and oxidative stress response in different drug-resistant cancers without affecting normal cells. I used several drug-resistant cancer cell lines (melanoma, colorectal, liver, and breast) and normal cells (melanocytes, colon cells, hepatocytes, and lung fibroblasts). As a result, I observed that AGP-induced intracellular reactive oxygen species (ROS) selectively kill several drug-resistant cancer cells (melanoma and colorectal) without affecting normal (non-cancerous) cells by activating tumor-necrosis factor (TNF) and Apoptosis signaling-regulating kinase 1 (ASK1) signaling pathways. In addition, I used animal (mice) experiments to evaluate the cytotoxic effects of AGP in in-vivo resistant tumor animal models. My other project was to study the impact of atmospheric pressure plasma and nanoparticles (carbon-nano tubes and graphene) in the proliferation and differentiation of human neural stem cells (NSCs), mesenchymal stem cells (hMSC), and embryonic stem cells (ESCs), which ultimately will help to use stem cell technology in degenerative diseases.

    2011- 2012    Supported by UW-MADISON AND SWEDISH RESEARCH MINISTRY FELLOWSHIP

    Project description: I developed several recombinant DNA plasmids and successfully injected them into Drosophila fruit flies to establish transgenic animal models to study the effects of transcriptional repressors and activators during embryonic development. Using Drosophila as a model system, I learned the impact of transcriptional repressors (Brakeless and Atrophin) on chromatin modification (histone acetylation and methylation) in epigenetic inheritance during animal development. Colleagues are now using my transgenic animals to study further and characterize Brakeless and Atrophin genes in diseases like diabetes.  

    2008-2011   Supported by NIH R21 DEVELOPMENTAL RESEARCH GRANT                        

    Project description: My systems biology approach to quantify the dynamics of innate immune response (IFN signaling) to virus infection helped us to determine “how gene order variants of vesicular stomatitis virus (VSV) activated differential protective immune response in prostate cancer cells.” I also found that one VSV gene order mutant (N3) could induce apoptosis in cancer cells efficiently and is more stable than the VSV mutant (M51R), which is now in clinical trials. In addition, I developed several fluorescence-based recombinant reporter vectors and integrated them into prostate cancer cells (stable cell lines) for live cell imaging. I also established transcriptional factors IRF3 and STAT1 knockdown prostate cancer stable cell lines using a lentiviral vector system to study several VSV mutants’ oncolytic (cancer-killing) effects in immune-competent or immune-deficient cancer cells. My observation (results) was central for defining a new five-year project in the systems biology of virus-cell interactions, a grant ranked among the top 7th percentile and funded by the US National Institutes of Health (NIH).

    2005 – 2008   Supported by CHINA MINISTRY OF SCIENCE PROGRAMME GRANT 863

    Project description: I found new cellular interacting partners of transcriptional factor NFκB and investigated their role in viral RNA transcription, viral replication, and virus-host interaction. I discovered that RNA helicase DDX1 interacts with NFκB-p65 for transcriptional activity and enhances HIV-1 viral transcription. I screened some effective siRNAs against cellular DEAD-box RNA helicase DDX1 and found them effective for inhibiting HIV-1 viral replication. I also studied the role of another RNA helicase, DDX3, in regulating HIV-1 transcription and replication