Iqbal Parker group
Our research interest is in the area of Molecular Biology and Genetics of Oesophageal Cancer focusing on genetic polymorphisms, gene mutations and deletions and the role of integrated foreign DNA (viral) in oesophageal cancer using a Whole Genome Sequencing approach.
We have completed an exploratory whole genome sequence analysis of a limited set of five patients and have identified a large number of unique aberrations, including insertions, deletions and movement of non-human genetic sequences. The most striking observation was the amplification and rearrangement of the Human Endogenous Retrovirus (HERV113) and the presence of a number of other viral DNA sequences.
We have been awarded a SA MRC/UK MRC/NEWTON fund grant to expand the scope of this study in collaboration with researchers at the Wellcome Trust Sanger Institute, (UK), Kings college London, Jomo Kenyatta University (Kenya), Sidney Brenner Institute (University of the Witwatersrand) and Walter Sisulu University (Eastern Cape).
Sanger has pioneered the use of massively parallel paired-end sequencing for the mapping of genomic rearrangements in cancer and have developed comprehensive bioinformatics algorithms for the identification of putative genomic rearrangements from massively parallel paired-end sequencing. Copy number aberrations will be extracted from exome deep sequencing data from the same set of samples using the EXCAVATOR algorithm. Validation of the top 50 mutations will be done by sequence analysis and copy number aberrations will be validated using high resolution Affymetrix SNP6 arrays on a subset of samples. The 50 top most likely driver genes will be identified using the data from mutation and copy number analysis. The classes of base substitutions detected in our discovery panel will be analysed to assess whether they correlate with any of the established mutation signatures associated with known environmental carcinogens such as tobacco smoke.
RNA sequencing of tumours will be performed using standard protocols to quantify the expression of all known genes. Analysis will include alignment of sequencing reads to the Genbank transcriptome and to the human reference genome. Potential fusion transcripts will be identified and matched to the genomic rearrangement data to assess biological validity.
Sequencing of a gene panel in South and East African patients will be done on a selection of ~100 genes identified in the discovery WGS and from genes frequently mutated in this tumour type in other populations. The targeted gene panel will be custom designed and sequenced using a Haloplex target enrichment kit (Agilent) that provides high coverage of target bases in paraffin-extracted DNA samples, and mutations called with SureCall software.
AT a translational level, this study will use the data generated to elucidate likely pathways of tumour development and to assess potentially actionable pathways with respect to known drugs (repurposing of known drugs) as well as the development of new drugs that influence these pathways.
List of students/postdocs
|Dr Kevin Dzobo||Senior Research Scientist, NRF Career Award Fellow|
|Fred Nindo||Postdoctoral Fellow|
|Ms Peris Wanjiru Wambugu||PhD|
|Ms Hendrina Shipanga||MSc|
|Ms Dimakatso Senthebane||MSc|
Paccez,J,D., Duncan, K., Vava, A., Correa, R.G., Libermann, TA., Parker, M.I. and Zerbini, L.F. (2015). Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in Oesophageal Squamous Cell Carcinoma. Mol. Biol. Cell. E14-04-0868. [Epub ahead of print] PMID:25568334.
Schäfer G, Hitchcock JK, Shaw TM, Katz, AA and Parker MI. (2015). A novel role of Annexin A2 in human type I collagen gene expression. J. Cell. Biochem. 116:408 - 417doi: 10.1002/jcb.24989. PMID: 25290763.
Matejcic M and Parker MI (2015). Gene-Environment Interactions in Oesophageal Cancer. Critical Reviews in Clinical Laboratory Sciences. 29 Jul 2015. DOI: 10.3109/10408363.2015.1020358.
Zhunussova G, Djansugurova L, Khussainova E, Zhunusbekova B, Afonin G, Khaidarova D, Parker MI. (2015). Analysis of K-ras codon 12 and TP53 mutations in patients with advanced colorectal carcinoma. South African Med. J. 105: 670-674.
Matejcic, M., Vogelsang, M., Wang, Y. and Parker M.I. NAT1 and NAT2 (2015). Polymorphisms, Environmental Exposure, and Susceptibility to Oesophageal Squamous Cell Carcinoma. BMC Cancer doi: 10.1186/s12885-015-1105-4.PMID: 25886288.
Dandara, C, Robertson, B, Dzobo, K and Parker, M.I. (2015). Patient and Tumour Characteristics as Prognostic markers for Oesophageal Cancer: a retrospective analysis of a cohort of patients at Groote Schuur Hospital. Eur J. Cardiothoracic Surgery. pii: ezv135. PMID: 25870217.
Dzobo K, Vogelsang M, and Parker MI. (2015). Wnt/β-catenin and MEK-ERK signaling are required for fibroblast-derived extracellular matrix-mediated endoderm differentiation of embryonic stem cells. Stem Cell Reviews and Reports May 29. [Epub ahead of print] PMID: 26022506).
Kaschula C, Hunter R, Cotton J, Ngarande E, Siyo V, Dzobo K, Schafer G, Lang D, Kusza D, Davies B and Parker, M.I. (2015). Ajoene, Anti-Cancer Agent from Garlic, Targets the Endoplasmic Reticulum Folding Pathway in Cancer Cells. Mol. Carcinog. 2015 Jul 24. doi: 10.1002/mc.22364. [Epub ahead of print].
Dzobo, K, Vogelsang M, Thomford, NE, Dandara C, Kallmeyer K, Pepper MS and Parker MI. (2016). Wharton’s Jelly-derived mesenchymal stromal cells and fibroblast-derived extracellular matrix synergistically activate apoptosis in a p21-dependent mechanism in WHCO1 and MDA MB 231 cancer cells in vitro" Stem Cells International. Article ID 4842134, dx.doi.org/10.1155/2016/4842134.
Smith M, Hunter, R, Stellenboom N, Kusza D, Parker MI, Hammouda ANH, Jackson G, and Kaschula CH. (2016). The cytotoxicity of garlic-related disulfides and thiosulfonates in WHCO1 oesophageal cancer cells is dependent on S-thiolation and not production of ROS. Biochem. Biophys. Acta, 1860, 1439-1449.
Burgoyne AR, Kaschula CH, Parker MI and Smith, GS (2016). In vitro Cytotoxicity of Half-Sandwich Platinum Group Metal Complexes of a Cationic Alkylated Phosphaadamantane Ligand. Eur. J. Inorg. Chem. DOI: 10.1002/ejic.201501458
Dzobo K, Turnley T, Wishart A, Rowe A, Kallmeyer A, van Vollenstee FA, Thomford NE, Dandara C, Chopera D, Pepper MA and Parker MI. (2016). Fibroblast-Derived Extracellular Matrix Induces Chondrogenic Differentiation in Human Adipose-Derived Mesenchymal Stromal/Stem Cells in Vitro. Int. J. Mol. Sci. 17, 1259; doi:10.3390/ijms17081259
Thomford NE, Mkhize B, Dzobo K, Mpye K, Rowe A, Parker MI, Wonkam A, Skelton M, September AV, Dandara C. (2016). African Lettuce (Launaea taraxacifolia) Displays Possible Anticancer Effects and Herb-Drug Interaction Potential by CYP1A2, CYP2C9, and CYP2C19 Inhibition. OMICS: A Journal of Integrative Biology, 20, 528-537. doi: 10.1089/omi.2016.0117
Dzobo K. Senthebane DA, Rowe A, Thomford NE, Mwapagha LM, Al-Aww ad N, Dandara C and Parker MI. (2016). Cancer Stem Cell Hypothesis for Therapeutics Innovation in Oncology? Taking the Root Out, Not Chopping the Leaf. OMICS: A Journal of Integrative Biology, 20(12):681-691. PMID: 27930094.
List of Collaborators
|Professor Peter Campbell||Senior Group Leader and Head of Cancer Genetics & Genomics||Wellcome Trust Sanger Institute, Cambridgeshire, UK|
|Professor Denver Hendricks||Medical Biochemistry and Structural Biology||UCT|
|Professor Philip H Jones||Programme Leader, MRC Cancer Cell Unit and Senior Faculty||Wellcome Trust Sanger Institute UK|
|Professor Virna Leaner||Medical Biochemistry and Structural Biology||UCT|
|Professor Christopher Mathew||Department of Medical & Molecular Genetics||King’s College London (UK)|
|Professor Steve Molaoa||Department of Surgery, Faculty of Health Sciences,||Walter Sisulu University, Eastern Cape, South Africa|
|Dr Eugene J. Ndebia||Department of Human Biology, Faculty of Health Sciences||Walter Sisulu University, Eastern Cape, South Africa|
|Dr Fred W Wamunyokoli||Jomo Kenyatta University of Agriculture and Technology||Nairobi, Kenya|
|Dr Pascale Willem||Head Somatic Cell Genetics Unit||NHLS, Johannesburg, South Africa|