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Dr. SUMETH Perera

Senior Lecturer

Medicine

Email : sumeth@med.sab.ac.lk

    Profile

  • BSc Hons Biochem (Bom), MPhil Biochem & Mol Biol (Pera), MRes, DIC Bio Med Sc (Imperial Col Lon), DPhil Physiol Anat Genet (Oxon)

    Postdoctoral Fellow, National Cancer Institute/NIH, USA

    As a translational cancer biologist I am interested in exploring how biochemical pathways and pharmacological interventions determine effective cancer therapies. A snapshot of my research displays how biological questions uncover regulatory mechanisms that control malignant changes in mammalian cells. My particular interest in PI3K-AKT-mTOR regulation of extracellular vesicles called exosomes and hairlike organelles called cilia have shaped my understanding about these powerful signaling platforms in membrane biology of cancer cell-cell communication.

    Scholarships and Awards:

     

    Oral and Poster Presentations:

    • Poster presentation at ASCB (American Society for Cell Biology) conference: ‘Initiation of primary cilium assembly requires a Rab effector switch,’ Washington DC, 7-11 Dec 2019.
    • Poster presentation at Advanced Technology Research Facility, Investigation of ciliogenesis dysfunction in cancer cells, Nov 2019.
    • FASEB Science Research Conference on ‘Small GTPases in Membrane Processes: Trafficking, Autophagy and Disease’ Leesburg, Virginia; Poster Presentation, 23rd-28th Sept 2018
    • Presenter for NCI/NIH at Science and Engineering Festival, Walter E. Washington Convention Center, 7th-8th April 2018 – Mitotic dysregulation in cancer
    • Poster for annual CRUK Oxford Symposium, 2015, Exosome Switching: an mTORC1 dependent cellular stress response
    • Poster for annual Oxford Developmental Biology Symposium, 2013
    • Oral presentation for Oxford Extracellular Vesicle Group Meeting, Oxford, 26 Nov 2014
    • Oral presentation for the International Society for Extracellular Vesicles (ISEV), Rotterdam, Netherlands, 30th April to 3rd May, 2014. The PI3K/mTORC1 Signalling Network Regulates the Cargo of Exosomes Secreted from HCT116 Colorectal Cancer Cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001129/

    Membership of Professional Bodies/Associations

  • 2020 National Postdoctoral Association 

    2019 American Society for Cell Biology (ASCB) https://www.ascb.org/

    2018 Federation for American Society for Experimental Biology (FASEB) https://www.faseb.org/

    2014 International Society for Extracellular Vesicles (ISEV) https://www.isev.org/

    2012 Life member of the Oxford Union

     

    Current Research Projects

    • Metabolic Stress Triggers Tumour Initiation in Oral Submucous Fibrosis: 

      Nutrient imbalance causes metabolic stress at cellular and organismal level. Diet-induced metabolic dysregulation especially lipid-dependent metabolic stress (LMS) is implicated in tumour initiation and metastasis.  In particular, certain fat receptors interact with several ECM molecules including integrins is a key upstream regulator in lipid metabolism and collagen degradation leading to pathogenesis of fat receptor-mediated signaling that disrupts ECM homeostasis.

      Oral Submucous Fibrosis (OSF) is a potentially malignant condition with 7-13% transformation rate, which is frequently found in South Asia and in the Western-Pacific. Areca-nut chewing that progressively restricts mouth opening contributes to diet related metabolic stress in OSF with nutritional complications. However, little is known about the malignant transformation of OSF that has undergone epithelial atrophy and submucosal fibrosis with signs of inflammation and immune reactivity. More recently, it was identified that an 80% of malignant transformed cases from OSF showed a significant upregulation of αvβ6 integrins and formed a unique population of keratinocytes with a potential for invasion and metastasis.

      The poor dietary habits following chronic impact on restricted mouth opening, OSF patients develop diet-related metabolic stress which we reckon to play a pivotal role in its malignant transformation.

    Recent Publications

    1. Zhao H, Sun J, Insinna C, Lu Q, Wang Z, Nagashima K, Stauffer J, Andresson T, Specht S, Perera S, Daar IO, Westlake CJ. Male infertility-associated Ccdc108 regulates multiciliogenesis via the intraflagellar transport machinery. EMBO Rep. 2022 Feb 24:e52775. doi: 10.15252/embr.202152775. Epub ahead of print. PMID: 35201641.  Impact Factor: 8.8
    2. Jermusyk A, Zhong J, Connelly KE, Gordon N, Perera S, Abdolalizadeh E, Zhang T, O'Brien A, Hoskins JW, Collins I, Eiser D, Yuan C; PanScan Consortium; PanC4 Consortium, Risch HA, Jacobs EJ, Li D, Du M, Stolzenberg-Solomon RZ, Klein AP, Smith JP, Wolpin BM, Chanock SJ, Shi J, Petersen GM, Westlake CJ, Amundadottir LT. A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer. Am J Hum Genet. 2021 Oct 7;108(10):1852-1865. doi: 10.1016/j.ajhg.2021.09.002. Epub 2021 Sep 23. PMID: 34559995; PMCID: PMC8546220. Impact Factor: 10.5
    3. Walia V, Cuenca A, Vetter M, Insinna C*, Perera S*, Lu Q, Ritt DA, Semler E, Specht S, Stauffer J, Morrison DK, Lorentzen E, Westlake CJ. AKT Regulates a Rab11-Effector Switch Required for Ciliogenesis. Dev Cell. 2019 Jul 22;50(2):229-246.e7. Impact Factor: 10.09
    4. Cris AP*, Perera SMW*. Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction. Yale J Biol Med. (2017); 90(4):625-634. Invited Review. Impact Factor: 3.549
    5. Redhai S, Hellberg JE, Wainwright M, Perera SW, Castellanos F, Kroeger B, Gandy C, Leiblich A, Corrigan L, Hilton T, Patel B, Fan SJ, Hamdy F, Goberdhan DC, Wilson C. Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells. PLoS Genet. (2016);12(10):e1006366. Impact Factor: 5.915
    6. Fan SJ, Snell C, Turley H, Li JL, McCormick R, Perera SM, Heublein S, Kazi S, Azad A, Wilson C, Harris AL, Goberdhan DC. PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer. Oncogene. (2016); 35(23): 3004-15. Impact Factor: 9.867
    7. Corrigan L, Redhai S, Leiblich A, Fan SJ, Perera SM, Patel R, Gandy C, Wainwright SM, Morris JF, Hamdy F, Goberdhan DC, Wilson C. BMP-regulated exosomes from Drosophila male reproductive glands reprogram female behavior. J Cell Biol. (2014); 206(5): 671-88. Impact Factor: 10.54
    8. Perera MWS, Gunasinghe D, Perera PAJ, Ranasinghe A, Amaratunga P, Warnakulasuriya S, Kaluarachchi K. Development of an in vivo mouse model to study oral submucous fibrosis. J Oral Pathol Med (2007); 36: 273-80. Impact Factor: 4.25