Member SpotlightsThe Integration of Proteomics with Tumor Cell Biology Research Adam Richardson, Ph.D. One of the newest members to The Science Advisory Board.  Adam Richardson in the lab at BIMR. Adam Richardson, Ph.D., is a Post-Doctoral Fellow for the Burnham Institute for Medical Research, one of the National Cancer Institute's Cancer Centers in the US. Richardson received his B.A. in Biochemistry/Biology and his M.S. in Environmental Engineering, both from Rice University. His doctoral work with Dr. Chris Ireland at the University of Utah allowed him to investigate antitumor drugs derived from natural marine sources. This initial research with tumor suppressants has led Richardson to his current research in tumor physiology at NCI; he currently explores tumor bioenergetics with Dr. Jeff Smith. In addition to his research, Richardson works as a grant reviewer for the U.S. Civilian Research and Development Foundation. Notable achievements include the following fellowships: the Eleanor and Mills Bennett Fellowship (1997), American Foundation for Pharmaceutical Education Predoctoral Fellowship (1999 and 2000), and the American Chemical Society (Medicinal Chemistry) Predoctoral Fellowship (2000). He was a recipient of the Burnham Science Network, NCI Cancer Center Symposium Award (2007). Richardson is also a member of Scientists and Engineers for America and the American Association for the Advancement of Science. Describe your current field of research and your motivations to continue work in tumor cell biology. I am interested in the bioenergetics of human tumors, especially the changes that occur in the cellular metabolic program during transformation. These changes are broadly referred to as the Warburg effect, although we are finding that there is much more complexity to the metabolic alterations than simply increased lactate production. As a senior postdoc in the Smith lab I am involved in all levels of the research process, from grant writing and project design to bench work. I am motivated by both the clinical and basic science aspects of my work. Tumor cell biology is an interesting combination of understanding the fundamental workings of a cell and applying this understanding in a medically meaningful way. Cancer is a devastating disease and any contribution I can make to treating or preventing tumor growth will make my efforts worthwhile. The difficulties we have in advancing patient care lie in the complexity of the disease and as a scientist I am intrigued by the challenge. What are your goals and career expectations for the future? My career path is roughly what I envisioned when I began research as an undergraduate, although it is a slower process than I expected. The length of the graduate school and post-doctoral process has greatly increased in the last decade, particularly in the life sciences. There needs to be a better system in place for allowing postdocs to move to a more permanent position. Alternately, the post-doctoral position itself could be reconfigured. I am fortunate in that both my institution and my PI provide excellent support for post-doctoral scientists. But the low pay and instability of the post-doctoral position will eventually deter young scientists from life science research. At the moment, my goal is to transition to an independent investigator position and to continue my work on cellular metabolism. I hope that eventually this work will lead to improved cancer therapies, ones that will help treat the disease without the side effects of current drugs. The “personalized medicine” paradigm is very promising and should make such treatments possible in the near future. Richardson comments on the future of proteomics technology and its integration with his current research. Please explain the integration of proteomics with your current research. We are working on all three levels of cellular systems control – transcription, translation and activity. Tumor progression involves all three mechanisms and understanding the disease will require describing all three as well. Obviously the genetic platforms are most advanced at the moment, and proteomics is rapidly catching up. Recent proteomic advances in identifying post-translational modification are a big step for the field. Phosphorylation, glycosylation and other modifications have a great impact on enzymatic activity and protein localization. Metabolomics is also experiencing dramatic growth. Eventually, systems biology will merge all these –omics into a true picture of what is happening inside a living cell. What particular tools or methods used in your lab are specific to proteomics? The Burnham Institute for Medical Research has several cutting-edge resources, including a Proteomics Core Facility. Dr. Jeff Smith is the director of the Core, and Dr. Khatereh Motamedchaboki is the manager. She facilitates protein separation and identification using several methods, including 2D gel electrophoresis and mass spectrometry. The Core currently operates LTQ, Q-TOF, MALDI, and HCTultra instruments and will soon install a LTQ OrbiTrap. Dr. Smith is also the director of the Center on Proteolytic Pathways (CPP), part of the NIH Roadmap Initiative. The CPP is a national resource devoted to mapping the substrate specificity of all human proteases, linking them to other cellular pathways and disseminating this information to the scientific community. This proteolytic map and other resources may be found at PMAP. 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? I believe that we are getting close. Our newly developed ability to quantify post-translational modifications is a much-needed advance. Additionally, high content imaging is greatly contributing to our knowledge of protein localization. I think the current challenges are extrapolating protein activity from expression and PTM data, as well as integrating this data into a coherent whole. How effective is today's technology to conduct large-scale, high-throughput analyses for the detection, identification, and functional investigation of low-abundant proteins? Our automation and detection technologies are definitely a step ahead of the rest of the process. The separation process is currently the main bottleneck in high-throughput proteomic analysis. Dr. Motamedchaboki, the manager of the BIMR Proteomics Core, is currently working on alleviating this limitation in our facility though the installation of a 4D separation step in front of the OrbiTrap mass spectrometer. We are also developing in-house software to deal with deconvoluting the resulting spectra. Eventually, all of this technology will allow us to fully move to label-free experimental setups where we can map native cellular proteins. Do you agree or disagree with the following statement? The major limitation of proteomic investigations today remains with the complexity of biological structures and physiological processes. I do agree. Currently, even if you are successfully able to identify and quantify most of the cellular proteome, it is difficult to translate that data into a meaningful description of the entire cell. The fault lies not in our instrumentation but in the natural complexity of biology. It will be interesting to watch systems biology in the next few decades and see if we are able to master this complexity or if there are emergent properties of the cell that remain unpredictable. 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? While not exactly an online database, I was a participant in the Human Proteome Folding Project. This was a distributed computing project by United Devices and Grid.org, which used Rosetta software to predict the structure of human proteins. ### << Previous Next >> [ View All Member Spotlights ] |
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