Member SpotlightsUtilization of Proteomics Applications in Cancer Stem Cell Research Feridoun Karimi-Busheri, Ph.D. A Science Advisory Board Member Since 2001  Feridoun Karimi-Busheri, Ph.D. Feridoun Karimi-Busheri, Ph.D., has recently joined NovaRx Corporation, US, as a Senior Investigator in cancer vaccine development with an emphasis on cancer stem cell research. For two decades prior to joining NovaRx, he worked for the Cross Cancer Institute, Canada, where the focus of his work was to, " find novel proteins involved in DNA repair and to explore mechanisms of sensitivity and the resistance of proteins to different genotoxic agents." Karimi-Busheri obtained his MS in genetics from the University of Ahwaz, Iran, and his Ph.D. is human genetics from Wales University, UK. His Ph.D. work on the genetics of intelligence was published in Nature, and was referred to in international media including a BBC TV scientific film. Research Interests A pinnacle achievement in my career has been finding the human polynucleotide kinase, the first DNA kinase/phosphatase protein in humans, in the laboratory of Dr. Michael Weinfeld. Since 2002, I have also been utilizing siRNA techniques in the transient and stable silencing of genes involved in DNA repair pathways in human lung and brain tumor cell lines. As I mentioned, I have recently moved to NovaRx Corporation as a Senior Investigator. This is a late clinical-stage biopharmaceutical company dedicated to the discovery of novel-based therapeutic vaccines for the treatment of various cancers. My role in NovaRx is to establish a Cancer Stem Cell Program for identification of anti-cancer drugs and utilization in the company’s different immune therapy programs. I have always been fascinated with the concepts of regeneration and stem cells. Similarity between cancer stem cells and stem cells are the main force of motivation driving me towards cancer stem cell research. Career Reflections My interest in the last two decades had focused primarily on the cancer biology of solid tumors. Cancer stem cells in these types of tumors are a new concept in tumor biology. My only regret is that I wish the stem cell origin of tumorigenesis was discovered earlier in my career. This would have given me the opportunity to see how this concept would have developed and to what extent humans can benefit from it. Nonetheless, I am quite satisfied and lucky to be actively involved in this field. The application of global characterization of the proteome in stem cells will be fundamental for cell-based therapies and will definitely improve our understanding of the origin of tumorigenesis at the cancer stem cells level. Leisure Time Activities I thoroughly enjoy writing short stories and literary criticisms in Persian, my mother tongue. I am a member of the Canadian Writer’s Association (PEN) and I frequently publish in Iranian literary magazines in North America and Europe. I also spend a lot of time painting water color, and have recently begun to try my hand at acrylic. Regrettably, I lack the talent I seek and thus, this pastime is purely therapeutic trial-and-error experience. The rest of my time is dedicated to soccer (primarily the English league), golf, tennis and everything else except baseball and cricket, sorry fans. The following questions are specific to our current Spotlight on Protein Science Research: Please explain the utilization of proteomics in your current research. My objectives are to direct proteomic studies towards therapeutically meaningful information. I attempt to understand how to use the information obtained from the proteome towards genes and pathways of interest. I find the similarities between the complexity of biological structures and physiological processes and of malignant tissues fascinating. Are their particular tools or methods used in your lab specific to proteomics? Microarray and chromatography plus subcellular fractionation are methods that I rely on. As proteomics is being applied to medical challenges with respect to the identification of new pathological markers and therapeutic targets, do you believe the current generation of proteomic tools can meet this challenge? Potentially, yes. As a new technology, however, there are hopes and hypes surrounding it. Proteomics has been successful in many diseases at fishing out potential biomarkers or candidate proteins that may be targets for drug development and therapies. In lung cancer, for example, TAO1/2 (napsin A) protein was discovered by proteomics analysis as a potential biomarker to identify the metastatic form of adenocarcinoma. How effective is today's technology to conduct large-scale, high-throughput analyses for the detection, identification, and functional investigation of low-abundant proteins? Low-abundant proteins still remains a real challenge in proteomics. Considering when samples are taken from patients at the early diagnostic stage, even the abundant proteins might be quantitatively low. There are many methods and techniques focusing on these proteins, but how much of this can be translated at high-throughput analyses at the functional level? I am not very optimistic. There is still a long way to go and much to find. Technology is improving and attempts like high-performing antibody microarrays are promising. There is only a matter of time to discover methods to detect low-abundant proteins at the desired quality and quantity. We should never forget that even in early 80s, DNA amplification was a dream. This may best be described by what Paul Rabinow wrote: “It makes abundant what was once scarce”. There are positive signs and tremendous research to overcome this. I am optimistic in the direction that nanotechnology is taking to build an interface with functional biology and medicine. Do you agree or disagree with the following statement? Please explain your rationale. The major limitation of proteomic investigations today remains with the complexity of biological structures and physiological processes. This indeed remains a challenge in proteomics as one of the most important “post-genome” technologies to elucidate genes and protein functions. Proteomics may satisfy a holistic vision of nature, and help us to regard creatures as whole entities that must be analyzed to fully understand the function of the particular organism. Holistic science has always been controversial because it does not meticulously follow the scientific method. On the other hand, this holistic approach of an organism’s protein expression might become a victim of itself, by losing the power of quantification, missing in the dynamic of organisms and the biological process. Research projects that aim to identify & catalogue the entire proteome for an organism is a giant undertaking. The result has been international collaborations & associations, often with online databases, that attempt to speed up this process by data sharing. Do you belong to any of these associations, and if so, do you find them effective? How do you think research at University of Alberta is contributing to the national & international efforts in proteomics? Today there is no boundary for proteome profiling as one of the fastest-growing areas in technology. Various databases intend to support research from microorganisms to human, specific tumors and non-cancerous tissues, fluids, serum, plasma, and different biological phenomenon such as aging, diseases, and more, are emerging. The University of Alberta is an active agent in the development of this field, including the Alberta Transplant Applied Genomics Centre that is utilizing “Omic” technologies to develop novel ideas to improve disease outcomes. To discuss proteomics and other topics with fellow Science Advisory Board members, please visit our community forum. Web Links Karimi-Busheri does not have a personal web site that concerns his research, but would like to recommend the following: Human Proteome Organization (UPO) ExPASy Molecular Biology Server Publications Karimi-Busheri, F., et al., Human polynucleotide kinase participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination. Cancer Res. 2007;67:6619-25. Rasouli-Nia*, A., Karimi-Busheri*, F., Weinfeld, M. Stable down-regulation of human polynucleotide kinase enhances spontaneous mutation frequency and sensitizes cells to genotoxic agents. PNAS., 2004 ;101:6905-10. Karimi-Busheri, F., et al., Expression of a releasable form of annexin II by human keratinocytes. J. Cell. Biochem. 2002;86:737-47. Meijer*, M, Karimi-Busheri, F.*, et al., Pnk1, a DNA kinase/phosphatase required for normal response to DNA damage by gamma-radiation or camptothecin in Schizosaccharomyces pombe. J Biol Chem. 2002 ;277:4050-5. Karimi-Busheri, F., et al., Molecular characterization of a human DNA kinase. J. Biol. Chem. 1999;274:24187-94. Karimi-Busheri, F., et al., Repair of DNA strand gaps and nicks containing 3'-phosphate and 5'-hydroxyl termini by purified mammalian enzymes. Nucleic Acids Res. 1998;26:4395-400. Beardmore JA, Karimi-Booshehri F. ABO genes are differentially distributed in socio-economic groups in England. Nature. 1983 ;303:522-4. ### << Previous [ View All Member Spotlights ] |
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