B.Sc. (HONS) Microbiology, Universiti Sains Malaysia
MSc (Oncology), The University of Nottingham, UK
PhD (Medicine), The University of Sydney, Australia
1. Targeting the intrinsic apoptosis pathway of Nasopharyngeal carcinoma (NPC) and cervical cancer with existing BH3 mimetics. Both NPC and cervical cancer are in the list of top 10 cancers in Malaysia. We utilize the three-dimensional spheroid model to study the growth, invasion and drug sensitivity of cancer cells as spheroids recapitulate tumor microenvironment and architecture more closely than the two-dimensional cell culture system. Our research interest has now been extended to exploring natural compounds as treatment strategies for NPC and cervical cancer treatment. 2. Elucidating the consequences of the intrinsic apoptosis pathway for melanomagenesis in a mouse melanoma model. Melanoma drug resistance is often attributed to defective apoptosis pathways. Links between the intrinsic apoptosis pathway and melanomagenesis have not been established in vivo. In this study we utilized a mouse melanoma model in which the Cdkn2a locus is knocked-out and RAS is constitutively active (Cdkn2a-/-, Tyr-HRAS; “control”). This mouse line was crossed to either a Noxa or a Puma-knockout line resulting in Cdkn2a -/-, Tyr-RAS, Noxa -/- (“Noxa-KO”) or Cdkn2a -/-, Tyr-RAS, Puma -/- (“Puma-KO”). Mice from all three cohorts are compared for tumor latency, penetrance, location and growth.
1. Manipulate pro-apoptotic protein NOXA to sensitize NPC cells to BH3 mimetic ABT-263. 2. To investigate the consequences of manipulating BH3-only proteins Puma and Noxa in the intrinsic apoptosis pathway for melanomagenesis and drug resistance in a mouse model of melanoma. 3. Investigate c-myc Gene Regulation in Cervical Cancer Cells via Disruption of CTCF/YB-1 Complex by HPV 16 and 18 E7 Oncoprotein. 4. Investigating the growth and invasion phenotypes of the 3D spheroids generated from cervical cancer cell lines with different HPV strain infection.
- INFORMM, Penang
- Institute for Medical Research (IMR), Kuala Lumpur
- The University of Queensland Diamantina Institute, QLD, Australia
- Centenary Institute, The University of Sydney, NSW Australia
- Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPHARM)
Peer-reviewed journal articles Kalaivani Muniandy*, Prabu Siva Sankar*, Benedict Lian Shi Xiang, Alan Khoo Soo- Beng, Venugopal Balakrishnan, Nethia Mohana-Kumaran. Establishment and Analysis of the 3-dimensional (3D) spheroids generated from the Nasopharyngeal Carcinoma cell line HK1. Proceedings 9th Regional IMT-GT UNINET Conference, November 2014, Penang, Malaysia. Tropical Life Sciences Research (special issue) (2015) (*equal first authors). Phang Su Ling, Keryn M. Lucas, Benjamin Roediger, Richard A. Scolyer, Wolfgang Weninger, John D. Allen, Nikolas K. Haass, Nethia Mohana-Kumaran. Absence of Noxa -/- delays melanomagenesis but accelerates melanoma growth in a mouse melanoma model [ABSTRACT]. Asia Pacific Journal of Molecular Biology & Biotechnology (APJMBB). 2015 vol 4. Benedict Lian Shi Xiang, Ooi Peng Xian, Hui Shin Yee, Alan Khoo Soo Beng, Nethia Mohana-Kumaran. Statins enhanced the sensitivity of the Nasopharyngeal Carcinoma cell line HK1 to BH3 mimetic ABT-263 [ABSTRACT]. Asia Pacific Journal of Molecular Biology & Biotechnology (APJMBB). 2015 vol 4. Yoon-Ming Chin, Taisei Mushiroda, Atsushi Takahashi, Michiaki Kubo, Gopala Krishnan, Lee-Fah Yap, Soo-Hwang Teo, Paul Vey-Hong Lim, Yoke-Yeow Yap, Kin-Choo Pua, Naoyuki Kamatani, Yusuke Nakamura, Choon-Kook Sam, Alan Soo-Beng Khoo, The Malaysian NPC Study Group (NM Kumaran was part of the NPC study group) and Ching-Ching Ng. HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese. International Journal of Cancer. 2015 Feb 1; 136 (3): 678 – 87. (online) (IF: 5.007). Mohana-Kumaran N, Hill DS, Allen JD, Haass NK. Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy. Pigment Cell Melanoma Research. 2014 July; 27 (4): 525-39 (IF: 4.619). [This publication was awarded the Universiti Sains Malaysia Sanggar Sanjung Award (publication category, November 2015] Kimberley A. Beaumont, Nethia Mohana-Kumaran and Nikolas K. Haass. Modeling Melanoma In Vitro and In Vivo. Healthcare. 2014, 2, 27-46 (IF: n.a; cover image). Wroblewski D, Mijatov B, Mohana-Kumaran N, Lai F, Gallagher S, Haass NK, Zhang XD, Hersey P. The BH3-mimetic ABT-737 sensitises human melanoma cells to apoptosis induced by selective BRAF inhibitors but does not reverse acquired resistance. Carcinogenesis. 2013 Feb; 34(2): 237-47 (IF: 5.266). Lucas KM#, Mohana-Kumaran N#, Lau D, Zhang XD, Hersey P, Huang D, Weninger W, Haass NK*, Allen JD*. Modulation of NOXA and MCL-1 as a strategy for sensitizing melanoma cells to BH3-mimetic ABT-737. Clinical Cancer Research. 2012 Feb 1;18(3): 783-795 (#equal first authors; *equal senior and corresponding authors) (IF: 8.722). [Our presentation of this study was awarded with the prize for the best oral presentation by a young investigator at the Australasian Society for Dermatology Research, May 2009]. Poh-Yin Yew, Taisei Mushiroda, Kazuma Kiyotani, Gopala Krishnan Govindasamy, Lee- Fah Yap, Soo-Hwang Teo, Paul Vey-Hong Lim, Selvaratnam Govindaraju, Kananathan Ratnavelu, Choon-Kook Sam, Yoke-Yeow Yap, Alan Soo-Beng Khoo, Kin-Choo Pua, Yusuke Nakamura and The Malaysian NPC Study Group (NM Kumaran was part of the NPC study group), Ching-Ching Ng. Identification of a Functional Variant in SPLUNC1 Associated With Nasopharyngeal Carcinoma Susceptibility Among Malaysian Chinese. Molecular Carcinogenesis. 2012 Oct; 51 Suppl 1:E74–E82 (IF: 4.808). Pua KC, Khoo AS, Yap YY, Subramaniam SK, Ong CA, Gopala Krishnan G, Shahid H; Malaysian Nasopharyngeal Carcinoma Study Group (NM Kumaran was part of the NPC study group). Nasopharyngeal Carcinoma Database. Med J Malaysia. 2008 Sep;63 Suppl C:59-62. Athanasiou, P. Smith, S. Vakilpour, N.M. Kumaran, A.E. Turner, D. Bagiokou, R. Layfield, D.E. Ray, A.D. Westwell, S.P.H. Alexander, D.A. Kendall, D.N. Lobo, S.A. Watson, A. Lophatanon, K.A. Muir, De-an Gino, Timothy E. Bates. (2007) Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: How vanilloids cause non-vanilloid receptor mediated cell death. Biochem. Biophys. Res. Com. 2007 Mar 2; 354 (1): 50-5 (IF: 2.28). Athanasiou, A.B Clarke, A.E. Turner, N.M. Kumaran, S. Vakilpour, P.A. Smith, D. Bagiokou, T.D. Bradshaw, A.D. Westwell, L. Fang, D.N. Lobo, CS. Constantinescu, V. Calabrese, A. Loesh, S.P. Alexander, R.H. Clothier, D.A. Kendall, Timothy E. Bates. Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of cannabinoids modulate mitochondrial function and induce cell death. Biochem. Biophys. Res. Com. 2007 Dec 7; 364 (1): 131-7 (IF: 2.28). Articles in science magazines and newspaper Nethia Mohana-Kumaran, Prabu Siva Sankar, Benedict Lian Shi Xiang, Kalaivani Muniandy. Modeling Cancer in Three-Dimension. Biobulletin. 2015 Apr/May: 9 Nethia Mohana-Kumaran. Science, Beach and Fun. Biobulletin. 2014 Jan/Feb: 30-31 Invited talks The Role of the Intrinsic Apoptosis Pathway for Melanomagenesis and Melanoma Therapy TRI Cancer Seminar Series The University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Australia, August 2015 How to write the results section of a thesis Final Year Project Students Thesis Writing Seminar School of Biological Sciences, Universiti Sains Malaysia, February 2014 The 3D Spheroid Model Provides Insight into The Difference in Sensitivity Of Noxa-Overexpressing Melanoma Cells to ABT-737 In Vitro and In Vivo. 2nd Seminar On Sustainable Agriculture and Natural Resources School of Biological Sciences, Universiti Sains Malaysia, Penang, Malaysia, April 2013 The Role of the Intrinsic Apoptosis Pathway for Melanomagenesis and Melanoma Therapy. Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Bertam, Penang, Malaysia, March 2013 The Role of the Intrinsic Apoptosis Pathway for Melanomagenesis and Melanoma Therapy. School of Biological Sciences, Universiti Sains Malaysia, Penang, Malaysia, February 2013 The Role of the Intrinsic Apoptosis Pathway for Melanomagenesis and Melanoma Therapy PhD Final Seminar, Centenary Institute, Sydney, NSW, Australia, September 2012 Modulation of NOXA and MCL-1 as a strategy for sensitising melanoma cells to ABT-737 loss of Noxa delay melanomagenesis in a predisposed, genetically-defined mouse melanoma model Florida International University, Florida, USA, November 2011 Technical panel discussion: “How to approach your research question from a cell signaling viewpoint” Centenary Institute, Sydney, NSW, Australia, October 2010 Awards Universiti Sains Malaysia Sanggar Sanjung Award (Publication category) (2015) International Travel Award awarded by the American Society of Cell Biology (ASCB) and the International Federation for Cell Biology (IFCB) to attend the 2014 ASCB/IFCB Meeting in Philadelphia, USA from December 6-10, 2014 The Best Oral Presentation by a Young Investigator Award 2011 was recognized as a significant achievement by The University of Sydney Medical School (2012) Best Oral Presentation by a Young Investigator Award – awarded at the Australasian Society for Dermatology Research, Perth, Western Australia (2011) Best Oral Presentation by a Young Investigator Award – awarded at the 6th Australasian Society for Dermatology Research, Surfers Paradise, QLD, Australia (2009) Centenary Institute for Cancer Medicine and Cell Biology Travel Award (2009) Cancer Institute New South Wales Scholar Award (2009) Academic Staff Training Scheme Fellowship awarded by the Ministry of Higher Education Malaysia to pursue PhD at the University of Sydney (2008-2012) Universiti Sains Malaysia Gold Medal for the best final year student in the field of Biology – awarded in memory of Professor E.Balasingham (2005) Dean’s List Award, Faculty of Biological Sciences, Universiti Sains Malaysia (2005) Dean’s List Award, Faculty of Biological Sciences, Universiti Sains Malaysia (2003) Dean’s List Award, Faculty of Biological Sciences, Universiti Sains Malaysia (2002) Student awards PhD candidate Kalaivani Muniandy received the MAKNA Cancer Research Award 2015 awarded by the National Cancer Council Malaysia for project “Investigating the growth and invasion phenotypes of the 3D spheroids generated from cervical cancer cell lines with different HPV strain infection” (RM 30,000 for two years 2015-2017) PhD student Kalaivani Muniandy received the award for the best poster at the 13th Symposium of Malaysian Society of Applied Biology, June, 2014, for her poster presentation “Establishing a Three-Dimensional (3D) Cell Culture Model from the Nasopharyngeal Carcinoma (NPC) Cell Line HK1: A Pilot Study” authored by Kalaivani Muniandy, Prabu Siva Sankar, Alan Khoo Soo Beng, Venugopal Balakrishnan, Nethia Mohana-Kumaran