On 25th January 2013, the National Research Foundation (NRF) announced the 6th cohort of young scientists to receive the prestigious Singapore NRF Fellowship. These 16 Fellows will join the ranks of 48 others since the award was started in 2007 and among them is Dr Karen Crasta from IMCB.
The aim of the Singapore NRF Fellowship is to attract young, promising and passionate researchers in various fields of science and technology to add to Singapore’s research talent pool and help sharpen our scientific and technological edge. The NRF Fellowship will provide each NRF Fellow with up to $3 million in research funding support over five years to perform cutting-edge research in Singapore
Dr. Karen Crasta was born in Singapore where she obtained her B. Sc. (Honours in Microbiology) and PhD in Cell Cycle Regulation from the National University of Singapore (NUS). During her PhD at the Institute of Molecular and Cell Biology (IMCB) in Prof. Uttam Surana’s laboratory, she studied the molecular circuits governing mitotic spindle assembly using budding yeast as a model system. In order to apply her interests in the basic mechanisms of mitosis directly to cancer, she then joined Prof. David Pellman's group at Dana-Farber Cancer Institute (DFCI), Harvard Medical School as a Howard Hughes Medical Institute Associate. In 2009, she was awarded the two-year A*STAR International Fellowship (AIF) to further support her postdoctoral studies which focused on elucidating the mechanistic link between chromosome mis-segregation and tumourigenesis. Since Feb 2012, Dr. Crasta has been working with Prof. Uttam Surana at the A*STAR IMCB where she is serving her 1 year bond period as part of the AIF requirements. Her study focuses on the understanding of the regulatory interface between the mitotic machinery, spindle assembly checkpoint and mitotic cell death/mitotic slippage following treatment of cancer cells with anti-mitotic drugs.
Dr. Crasta’s graduate work at IMCB was the first to elucidate the mechanistic role of the master kinase Cdk1 in centrosome separation and mitotic spindle assembly (Crasta et al., 2006, EMBO). This uncovered an unexpected novel regulatory role for the Polo kinase where it acts as part of a regulatory circuit involving Cdk1, Polo kinase, Cdh1 and kinesins for efficient spindle assembly (Crasta et al., 2008, Nature Cell Biology). This helped pave the way for subsequent studies describing how this regulatory circuit is also evoked by the DNA damage checkpoint to prevent segregation of damaged chromosomes. She also contributed to a study demonstrating that the replication checkpoint restrains entry into mitosis and spindle elongation (Krishnan et al., 2004, Molecular Cell). Dr. Crasta’s postdoctoral work at Harvard Medical School demonstrated that chromosome segregation errors due to improper spindle assembly could cause DNA damage and chromosomal breaks via asynchronous and replication-defective micronuclei. This finding provided a direct mechanistic link between chromosome segregation errors and cancer-causing mutations and may explain a new phenomenon in human cancer known as chromothripsis, where a single chromosome or chromosome arm appears to undergo massive breakage and rearrangement (Crasta et al., 2012, Nature). Dr. Crasta has extensive expertise in chromosomal analysis and has trained several groups in Singapore in specialized methodologies.
Understanding the molecular mechanisms leading to different cell fates upon treatment with anti-mitotic drugs has important implications for chemotherapy and is highly-relevant on a global scale. Dr. Crasta’s proposed research hopes to identify novel cellular targets that could be of relevance to the development of combination therapies to improve sensitization of tumour cells (enhancing efficacy and sensitivity of existing anti-mitotic drugs), and provide insights into chemoresistance, a major setback in oncology. Her research will involve multidisciplinary collaboration with scientists and clinicians in Singapore which is well-integrated into Singapore’s R&D objectives. She intends to utilize techniques such as cell biological and biochemical tools, genome-wide screening, next-generation sequencing, bioinformatics and animal studies. To better understand how to adapt her research for maximum clinical impact, Dr. Crasta has participated in the highly-selective “AACR 2012 Translational Cancer Research for Basic Scientists Workshop” organized by the American Association of Cancer Research.