Member SpotlightsThe Caldwell Lab Investigates Neurodegenerative Diseases at The University of Alabama Guy Caldwell, Ph.D. A Science Advisory Board Member Since 1999  Caldwell Lab a.k.a. "The Worm Shack". Guy Caldwell, Ph.D, is an Associate Professor of Biological Sciences at The University of Alabama, USA. Caldwell received his B.S. in Biology from Washington & Lee University, and his Ph.D. in Cell and Molecular Biology from The University of Tennessee before pursuing postdoctoral studies in Neurogenetics at Columbia University. He was named a Basil O'Connor Scholar of The March of Dimes Birth Defect Foundation, and also serves on the National Science Foundation Leadership Board and the Carnegie Foundation and Council for the Advancement and Support of Education (CASE). In 2007 the Caldwell Lab received funding from the Michael J. Fox Foundation for Parkinson's research (one of nine groups worldwide). For this work in neurogenerative diseases, he has received grants from the Parkinson's Disease Foundation, The Parkinson's Institute, and the Dystonia Medical Research Foundation, among others. Caldwell was awarded the CASE U.S. Professor of the Year Award for Alabama in 2005 for his dedication to neuroscience research and teaching. Describe your occupation and research interests at The University of Alabama. I am a professor and principal investigator of a research laboratory that uses the nematode roundworm, Caenorhabditis elegans, as a model system to study diseases of the nervous system. I also have the good fortune of sharing my laboratory and research career with my lovely wife and fellow UA professor, Dr. Kim Caldwell. Our lab is nicknamed “The Worm Shack”, and we have 9 graduate students and 15 undergraduates, 2 technicians, and 2 Ph.D.-level scientists, all currently "worming" out cures to diseases. What motivated you to pursue research in neuropathology? Our aging population is confronted with serious challenges in terms of the increased levels of neurological disorders and I felt there is a serious need for our society to rapidly find causes and cures to these debilitating diseases before they become overwhelming to our healthcare system (which is quite broken already!). On a personal note, my mother suffered from neurological dementia and watching her deterioration was hard and an inspiration to prevent others from having to witness their loved ones suffer in this manner. Has your career turned out as expected, and what are your hopes for future progress? My career path has been far greater then I could have ever imagined. Sometimes I cannot believe I get paid to do what I do. I have made amazing friends, truly from around the world, and had the most wonderful experiences all the way from graduate school to now. Running an academic research lab is “the life of the mind” and exploring the inner workings of our cells, our neurons, our brains is beyond fascinating – it is a blissful addiction. I want to unequivocally know that our lab has seriously contributed to a cure for a neurological disease. More importantly, my greatest contribution to science is the students I am privileged to train, as they are the finest product of our research lab. What are your hobbies and interests outside of the lab? I am a big believer in the fact that science is one of our greatest creative endeavors and try to surround myself with things that inspire my own creativity…I play piano and collect art (Marc Chagall is my favorite). I also have a sincere love of live theatre. Beyond the arts, I am a huge sports nut...especially of the (26-time world champion) New York Yankees. Having a lab in Alabama has also converted this former Tennessee Volunteer into a big fan of the Alabama Crimson Tide. A winning tradition rivaled only by my beloved Yankees….Roll Tide! These questions are specific to research in neuroscience: What neurodegenerative diseases are you currently investigating? Our lab is primarily focused on two human movement disorders: Parkinson’s Disease and dystonia. While PD is well known and afflicts over 1 million people in America alone, dystonia is a more rare disorder, but combined forms of this disease affects more people than Huntington’s, ALS, and muscular dystrophy – combined. Does your research involve pathologies more related to movement & motor coordination or memory loss and dementia? Or both? While PD involves age-dependent neuron loss, dystonia patients have intact neurons, but they are malfunctioning. These human movement disorders represent a significant societal burden. There are reasons to believe that common cellular pathways involved with Parkinson’s and Alzheimer's disease may exist and that a greater understanding of PD may contribute to our comprehension of dementias and AD. What strategies are you applying that will help alleviate neurodegenerative diseases? Our lab is taking a very different approach from many other researchers in this field, as we are using a microscopic worm to discern genetic susceptibility factors and novel therapeutic targets. This animal shares nearly 70% of genes that are linked to human diseases with us, as well as conserved neuronal mechanisms, thus it is worthwhile utilizing it as a more rapid means towards gene and drug discovery. Plus, there is a reason both the 2002 and 2006 Nobel Prizes in Medicine were awarded to worm researchers – it is simply a fantastic experimental system (not to mention cost-effective too). Are their particular pieces of lab equipment that are utilized extensively in your research? We use a wide range of tools from DNA microinjection systems, to fluorescent microscopy, thermocyclers, and other molecular biology methods. We have also done quite a bit using RNA interference, as the RNAi revolution was also started in worms nearly a decade ago. We dabble in mass spectrometry analysis and protein-protein interaction screening.  Guy Caldwell, Ph.D, with wife and research partner Kim Caldwell, Ph.D. Kim Caldwell is an Assistant Professor in the Department of Biological Sciences at The University of Alabama, and joined The SAB in 2001. Are you involved with the clinical side of neurodegenerative studies as well? Yes, we have done extensive chemical screens for drugs that may impact PD and dystonia. In this regard, we have partnered with biotechnology companies to form a pipeline that will enable us to take our findings “up the line” to mammals and human trials. We have recently received a significant sponsored research agreement with an exciting new Australian-based clinical-stage pharmaceutical company, QRxPharma, who is planning to run clinical trials based on some of our work. The thought that something we have discovered using a microscopic worm might actually make it to human clinical trials is thrilling. Moreover, it makes students realize that what they are doing enroute to a degree may have a tangible impact for patients. The fields of neuroscience in general, and neuropathology in particular, have generated much scientific interest and general media coverage. Do you think that the interest and funding for neurodegenerative diseases would be just as strong without the support of famous advocates who have experienced such a disease firsthand? Do you view this as having a negative or positive impact? Given the suffering and growing burden of these disorders in our society, there simply cannot be enough emphasis or attention directed to the need for a cure sooner rather then later, as the Baby Boomer population enters retirement age and beyond. In this regard, we must recognize that anything or anyone that raises awareness, money, or convinces people that their tax dollars are well spent in the area of biomedical research is a most positive force. Our own lab is fortunate to now be twice funded, as one of only 9 groups in the world, by the Michael J Fox Foundation for Parkinson’s Research this year. It remains a great honor and privilege to represent the research goals of this fine and innovative organization. People like Michael, Muhammad Ali, Christopher Reeve, and others serve to remind us each of our vulnerability, and the need to make a difference, not for saving a celebrity, but for sparing all of us. In regards to future developments, what type of breakthrough do you predict may occur in the future and when? When will new technology be available that will increase the speed & productivity of your research? Predictions are probably best left to the crystal ball and clairvoyants, but I can unequivocally state that our molecular understanding of neurological diseases like PD, AD, and dystonia is exponentially growing. While a lack of funding currently precludes some of the most exciting technological advances enabled by instrumental advances in genomics, proteomics, and bioimaging from being more widely applied in the field, there is much optimism that mechanistic advances in this research will drive more effective target identification, validation, and drug development. I firmly believe we will see new classes of small molecules and other therapeutic advances in the next 5-10 years for these diseases that will not come purely from serendipity, but from painstaking experimental advances stemming from our cumulative basic research knowledgebase. The greatest obstacle facing our ability to find cures is not creativity, technology, or hard work, it is funding for this research, as nearly 92% of grants to established investigators at the NIH are being declined for a lack of funds today. It is most unfortunate that 3000 people (including two friends of mine) were lost in 9/11, but 4200 people die every day of just 5 diseases (Alzhiemer’s, stroke, cancer, heart disease, diabetes). We have another war to win and IF we stand a chance of winning, we must “support the troops” in the trenches of the labs. No two ways about it; progress toward cures will be inexorably linked to such support. To discuss neuroscience research and other topics with fellow Science Adivisory Board members, please visit our community forum. The Caldwell Lab website featuring current research endeavors and "The Worm Shack" can be found here. The following are notable press releases and publications authored and co-authored by Caldwell that are relevant to this Member Spotlight. Press Releases Dr. Guy Caldwell – 2005 Alabama Professor of the Year Protector of Dopamine Neurons Identified, UA Parkinson's Researchers on Team Publishing Discovery in Science TorsinA Protein Protects Against Neuron Loss in Model for Parkinson's Disease Convulsions in Worms Mimic Epileptic Seizures Publications Hamamichi, S., Rivas, R.N., Knight, A.L., Cao, S., Caldwell, K.A., and Caldwell, G.A. (2008) Hypothesis-based RNAi Screening Identifies Neuroprotective Genes in a Parkinson's Disease Model. Proc. Natl. Acad. Sci. USA, in press. Cooper, A.A., Gitler, A.D., Cashikar, A., Haynes, C.M., Hill, K.J., Bhullar, B., Liu, K., Xu, K., Strathearn, K.E., Liu, F., Cao, S., Caldwell, K.A., Caldwell, G.A., Marsischky, G., LaBaer, J., Rochet, J-C., Bonini, N.M., and Lindquist, S. (2006) Alpha-synuclein blocks ER to Golgi trafficking in Parkinson's disease models. Science, 313:324-328. Cao, S., Gelwix, C.C., Caldwell, K.A., and Caldwell, G.A. (2005) Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans. J. Neuroscience, 25:3810-3812. Williams, S.N., Locke, C.J., Braden, A.L., Caldwell, K.A., and Caldwell, G.A. (2004) Epileptic-like convulsions associated with LIS-1 in the cytoskeletal control of neurotransmitter signaling in C. elegans. Human Molecular Genetics, 13:2043-2059. Caldwell G.A., Cao S., Sexton E.G., Gelwix C.C., Bevel J.P., and Caldwell K.A. (2003) Suppression of Polyglutamine-induced Protein Aggregation in Caenorhabditis elegans by Torsin Proteins. Human Molecular Genetics, 12:307-319. ### << Previous Next >> [ View All Member Spotlights ] |
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