Research
The Caldwell Laboratory (a.k.a, The Worm Shack) at The University of Alabama is studying malfunction in basic cellular and organismal mechanisms associated with diseases of the nervous system. Our laboratory utilizes the microscopic nematode roundworm, C. elegans, as a model system for discovering gene function, as well as therapeutic target development, and drug discovery. Research in The Shack is dynamic and continually evolving, but current efforts are on focused on investigations of Alzheimer’s disease, human movement disorders, including Parkinson’s Disease and dystonia, as well as epilepsy and other rare diseases.
C. elegans affords many advantages in such research as it is amenable to genetic, genomic, proteomic, and drug screening strategies and is an animal with a completely defined cell lineage, completed genome sequence, and lifespan of approximately 2-3 weeks. As opposed to the human brain, where it is estimated we have over 100 billion nerve cells, this microscopic worm contains precisely 302 neurons for which a defined neuronal connectivity map has been determined (WormAtlas.org). In this regard, C. elegans is ideal for investigation of diseases associated with neuronal dysfunction and aging. The substantial advantages of C. elegans as a model system to reveal major biological processes are exemplified by the fact that this animal was a subject of The Nobel Prize in 2002, 2006, 2008, and 2024. Importantly, beyond its preeminent role in basic research, C. elegans models of disease have reproducibly proven their utility as a preclinical system for biomedical research discovery.
If you are not familiar with this amazing worm, please see our Publications page for some excellent review articles. Recent publications from our group highlight use of C. elegans as a means to uncover critical and translationally significant disease mechanisms. Additionally, we have functionally discerned the significance of previously uncharacterized genes and human genomic variation in Parkinson’s and Alzheimer’s disease.
Current and recent work in the Caldwell Lab is funded by grants from the NSF, NIH, Howard Hughes Medical Institute, Michael J. Fox Foundation, in addition to numerous other biomedical foundations and patient support groups, as well as the pharmaceutical industry.
Research from our lab has been featured in the journals Science, Cell, Cell Metabolism, Nature Genetics, PLoS Genetics, Human Molecular Genetics, Nature Biomedical Engineering, J. Neuroscience, Molecular Cell, iScience, Human Molecular Genetics, Disease Models and Mechanisms, Cell Death and Disease, Nature Neuroscience, EMBO Molecular Medicine, and Molecular Neurobiology, among other respected venues. We are particularly proud that student researchers in our lab, including undergraduates, have co-authored seven papers in the Proceedings of the National Academy of Sciences (PNAS).
While microscopic worms are certainly our thing, we also conduct a variety of studies using mammalian cell cultures and biochemical assays. Numerous collaborative projects in the realm of human genetics, epigenetic regulation of neurodegeneration, mammalian target validation, molecular toxicology, and drug discovery are ongoing.
Former students trained in The Caldwell Lab have earned admission to professional programs at MIT., UCSF, Duke, Vanderbilt, Princeton, Stanford, Rockefeller, UNC-Chapel Hill, UT-Southwestern, U. Maryland, U. Michigan, Emory, Oxford, Cambridge, Harvard, U. Penn., Georgetown, as well as government organizations (NIH, DoD, USAMRIID, and the CIA). Among our student alumni from The Worm Shack are numerous successful industry scientists at Novartis, Pfizer, Genentech, PacBio, Revvity, Astra-Zeneca, Gilead Sciences, Novogene, and Neuro23 (including its founder!).
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