Ahmed Khairallah Mahdi

@nahrainuniv.edu.iq

Al-Nahrain University / College of Medicine



                 

https://researchid.co/ahmedk.mahdi

EDUCATION

MBChB, MSc Histopathology, PhD Molecular Pathology

5

Scopus Publications

70

Scholar Citations

2

Scholar h-index

2

Scholar i10-index

Scopus Publications

  • Immunohistochemical expression of CD117 in borderline, low-and high-grade ovarian surface epithelial tumours: A clinicopathological study


  • Single-Step Genome Editing of Small Ruminant Embryos by Electroporation
    Ahmed K. Mahdi, Juan F. Medrano, and Pablo J. Ross

    MDPI AG
    We investigated the possibility of single-step genome editing in small ruminants by CRISPR-Cas9 zygote electroporation. We targeted SOCS2 and PDX1 in sheep embryos and OTX2 in goat embryos, utilizing a dual sgRNA approach. Gene editing efficiency was compared between microinjection and three different electroporation settings performed at four different times of embryo development. Electroporation of sheep zygotes 6 h after fertilization with settings that included short high-voltage (poring) and long low-voltage (transfer) pulses was efficient at producing SOCS2 knock-out blastocysts. The mutation rate after CRISPR/Cas9 electroporation was 95.6% ± 8%, including 95.4% ± 9% biallelic mutations; which compared favorably to 82.3% ± 8% and 25% ± 10%, respectively, when using microinjection. We also successfully disrupted the PDX1 gene in sheep and the OTX2 gene in goat embryos. The biallelic mutation rate was 81 ± 5% for PDX1 and 85% ± 6% for OTX2. In conclusion, using single-step CRISPR-Cas9 zygote electroporation, we successfully introduced biallelic deletions in the genome of small ruminant embryos.

  • Key features of the environment promoting liver cancer in the absence of cirrhosis
    Marco Youssef William Zaki, Ahmed Khairallah Mahdi, Gillian Lucinda Patman, Anna Whitehead, João Pais Maurício, Misti Vanette McCain, Despina Televantou, Sameh Abou-Beih, Erik Ramon-Gil, Robyn Watson,et al.

    Springer Science and Business Media LLC
    AbstractThe prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) is rising, even in the absence of cirrhosis. We aimed to develop a murine model that would facilitate further understanding of NAFLD-HCC pathogenesis. A total of 144 C3H/He mice were fed either control or American lifestyle (ALIOS) diet, with or without interventions, for up to 48 weeks of age. Gross, liver histology, immunohistochemistry (IHC) and RNA-sequencing data were interpreted alongside human datasets. The ALIOS diet promoted obesity, elevated liver weight, impaired glucose tolerance, non-alcoholic fatty liver disease (NAFLD) and spontaneous HCC. Liver weight, fasting blood glucose, steatosis, lobular inflammation and lipogranulomas were associated with development of HCC, as were markers of hepatocyte proliferation and DNA damage. An antioxidant diminished cellular injury, fibrosis and DNA damage, but not lobular inflammation, lipogranulomas, proliferation and HCC development. An acquired CD44 phenotype in macrophages was associated with type 2 diabetes and NAFLD-HCC. In this diet induced NASH and HCC (DINAH) model, key features of obesity associated NAFLD-HCC have been reproduced, highlighting roles for hepatic steatosis and proliferation, with the acquisition of lobular inflammation and CD44 positive macrophages in the development of HCC—even in the absence of progressive injury and fibrosis.

  • Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification
    Leqian Yu, Yulei Wei, Hai-Xi Sun, Ahmed K. Mahdi, Carlos A. Pinzon Arteaga, Masahiro Sakurai, Daniel A. Schmitz, Canbin Zheng, Emily D. Ballard, Jie Li,et al.

    Elsevier BV

  • Targeting negative regulation of p53 by MDM2 and WIP1 as a therapeutic strategy in cutaneous melanoma
    Chiao-En Wu, Arman Esfandiari, Yi-Hsuan Ho, Nan Wang, Ahmed Khairallah Mahdi, Erhan Aptullahoglu, Penny Lovat, and John Lunec

    Springer Science and Business Media LLC
    Background:Cutaneous melanoma is the most serious skin malignancy and new therapeutic strategies are needed for advanced melanoma. TP53 mutations are rare in cutaneous melanoma and hence activation of wild-type p53 is a potential therapeutic strategy in cutaneous melanoma. Here, we investigated the WIP1 inhibitor, GSK2830371, and MDM2–p53 binding antagonists (nutlin-3, RG7388 and HDM201) alone and in combination treatment in cutaneous melanoma cell lines and explored the mechanistic basis of these responses in relation to the genotype and induced gene expression profile of the cells.Methods:A panel of three p53WT (A375, WM35 and C8161) and three p53MUT (WM164, WM35-R and CHL-1) melanoma cell lines were used. The effects of MDM2 and WIP1 inhibition were evaluated by growth inhibition and clonogenic assays, immunoblotting, qRT–PCR gene expression profiling and flow cytometry.Results:GSK2830371, at doses (⩽10 μM) that alone had no growth-inhibitory or cytotoxic effects on the cells, nevertheless significantly potentiated the growth-inhibitory and clonogenic cell killing effects of MDM2 inhibitors in p53WT but not p53MUT melanoma cells, indicating the potentiation worked in a p53-dependent manner. The siRNA-mediated knockdown of p53 provided further evidence to support the p53 dependence. GSK2830371 increased p53 stabilisation through Ser15 phosphorylation and consequent Lys382 acetylation, and decreased ubiquitination and proteasome-dependent degradation when it was combined with MDM2 inhibitors. These changes were at least partly ATM mediated, shown by reversal with the ATM inhibitor (KU55933). GSK2830371 enhanced the induction of p53 transcriptional target genes, cell cycle arrest and apoptosis.Conclusions:GSK2830371, a WIP1 inhibitor, at doses with no growth-inhibitory activity alone, potentiated the growth-inhibitory and cytotoxic activity of MDM2 inhibitors by increasing phosphorylation, acetylation and stabilisation of p53 in cutaneous melanoma cells in a functional p53-dependent manner.

RECENT SCHOLAR PUBLICATIONS

  • Key features of the environment promoting liver cancer in the absence of cirrhosis
    MYW Zaki, AK Mahdi, GL Patman, A Whitehead, JP Maurcio, MV McCain, ...
    Scientific reports 11 (1), 16727 2021

  • OP-01 Genome wide RNA expression analysis identifies CD44 positive macrophages as promoters of hepatocyte proliferation and the development of NAFLD-HCC
    HLR Marco Youssef William Zaki, Misti V McCain, Ahmed K Mahdi, Joao Mauricio ...
    EASL HCC summit 2019 2019

  • Liquid Biopsy-A New Prospect.
    AK Mahdi
    Iraqi Journal of Medical Sciences 16 (4) 2018

  • What drives development of HCC in non-cirrhotic NAFLD?
    A Mahdi, M Zaki, J Lunec, Q Anstee, D Tiniakos, R Shukla, F Oakley, ...
    Journal of Hepatology 68, S49 2018

  • Targeting negative regulation of p53 by MDM2 and WIP1 as a therapeutic strategy in cutaneous melanoma
    CE Wu, A Esfandiari, YH Ho, N Wang, AK Mahdi, E Aptullahoglu, P Lovat, ...
    British journal of cancer 118 (4), 495-508 2018

  • Molecular pathology: the roles of P53 in the oxidative stress and DNA damage responses in chronic liver disease and hepatocellular carcinoma
    AK Mahdi
    Newcastle University 2018

  • Lipogranulomas, neutrophils and the progression of NAFLD to NASH and HCC
    JC Mauricio, AK Mahdi, J Lunec, G Patman, A Whitehead, D Tiniakos, ...
    HEPATOLOGY 66, 987A-988A 2017

  • MDM2 inhibition for non-genotoxic activation of TP53-a novel strategy for the treatment of hepatocellular carcinoma (HCC)
    AK Mahdi, HD Thomas, S Wedge, R Shukla, H Reeves, J Lunec
    HEPATOLOGY 66, 369A-369A 2017

  • Inhibition of WIP1/PPM1D phosphatase by GSK2830371 potentiates the growth inhibitory and cytotoxic activity of MDM2 antagonists (nutlin-3, RG7388 and HDM201) in cutaneous
    CE Wu, A Esfandiari, YH Ho, C Shepherd, AK Mahdi, E Aptullahoglu, ...
    Cancer Research 77 (13_Supplement), 2151-2151 2017

  • Abstract P3-07-21: Cytotoxic potential of the RG7388 MDM2-p53 binding antagonist and the GSK2830371 WIP1 inhibitor on MX-1 and MCF-7 human breast cancer cells
    V Manoharan, J Lunec, A Esfandiari, A Mahdi, CE Wu, M Zanjirband, ...
    Cancer Research 77 (4_Supplement), P3-07-21-P3-07-21 2017

  • Cytotoxic potential of the RG7388 MDM2-p53 binding antagonist and the GSK2830371 WIP1 inhibitor on MX-1 and MCF-7 human breast cancer cells
    V Manoharan, J Lunec, A Esfandiari, A Mahdi, CE Wu, M Zanjirband, ...
    CANCER RESEARCH 77 2017

  • MDM2 antagonists− a therapeutic approach for patients with hepatocellular carcinoma?
    A Mahdi, J Lunec, H Reeves
    European Journal of Cancer 1 (61), S44 2016

  • Bcl-2 Expression in CagA Strain H. Pylori Gastritis (Immunohistochemical and Insitu Hybridization Study)
    HH Ali, HA Hassan, BAA Hassan, TW Ali
    Iraqi Postgraduate Medical Journal 11 (1) 2012

  • Lymphocyt e Predominance Hodgkin Lymphoma Clinicopathological an d Immunohistochemical Interpretations Using CD15 and CD20
    YE Abdul-Qadir, AK Chaloob, AK Mahdi
    The Iraqi Postgraduate Medical Journal 7, 25-30 2008

  • Iraqi JMS
    TW Ali, AK Mahdi, HH Ali, HA Hassan
    IRAQI JOURNAL OF MEDICAL SCIENCES, 160 2000

MOST CITED SCHOLAR PUBLICATIONS

  • Targeting negative regulation of p53 by MDM2 and WIP1 as a therapeutic strategy in cutaneous melanoma
    CE Wu, A Esfandiari, YH Ho, N Wang, AK Mahdi, E Aptullahoglu, P Lovat, ...
    British journal of cancer 118 (4), 495-508 2018
    Citations: 56

  • Key features of the environment promoting liver cancer in the absence of cirrhosis
    MYW Zaki, AK Mahdi, GL Patman, A Whitehead, JP Maurcio, MV McCain, ...
    Scientific reports 11 (1), 16727 2021
    Citations: 11

  • Inhibition of WIP1/PPM1D phosphatase by GSK2830371 potentiates the growth inhibitory and cytotoxic activity of MDM2 antagonists (nutlin-3, RG7388 and HDM201) in cutaneous
    CE Wu, A Esfandiari, YH Ho, C Shepherd, AK Mahdi, E Aptullahoglu, ...
    Cancer Research 77 (13_Supplement), 2151-2151 2017
    Citations: 1

  • Abstract P3-07-21: Cytotoxic potential of the RG7388 MDM2-p53 binding antagonist and the GSK2830371 WIP1 inhibitor on MX-1 and MCF-7 human breast cancer cells
    V Manoharan, J Lunec, A Esfandiari, A Mahdi, CE Wu, M Zanjirband, ...
    Cancer Research 77 (4_Supplement), P3-07-21-P3-07-21 2017
    Citations: 1

  • Lymphocyt e Predominance Hodgkin Lymphoma Clinicopathological an d Immunohistochemical Interpretations Using CD15 and CD20
    YE Abdul-Qadir, AK Chaloob, AK Mahdi
    The Iraqi Postgraduate Medical Journal 7, 25-30 2008
    Citations: 1