Professor, Physiology and Biophysics
Research OverviewThe Town lab joined the Zilkha Neurogenetic Institute on May 1, 2013. My labs focus is to develop a treatment for Alzheimer's disease by targeting the bodys immune system. Most therapies targeting the disease are thwarted by the blood-brain barrier, a natural mechanism that protects brain cells from entry of peripheral substances, and by the fact that immune responses in the brain are typically muted. However, in laboratory mice programmed to develop Alzheimer's-like disease, my group has shown that certain immune cells can be coaxed into the brain from the circulation, where they attack the damaging sticky plaque buildup that is a defining feature of Alzheimer's disease.
My lab is continuing to pursue this line of research in hopes of developing a next-generation drug for Alzheimer's disease. This work, which has been funded by the National Institutes of Health, the Alzheimer's Association, and the American Federation for Aging Research, has been published in numerous high-impact peer-reviewed journals including Science, Nature Neuroscience, Immunity, PNAS, and The Journal of Neuroscience. Of the over 100 research papers that we have published, half have been related to Alzheimer's disease.
Earlier this year, my lab revolutionized the field of Alzheimers disease research by generating the first rat model of the disease that manifests all of the clinico-pathological hallmarks of the human syndrome. Specifically, we made transgenic rats that over-express two mutant human transgenes that are each independently causative of familial early-onset Alzheimers disease: Swedish mutant amyloid precursor protein and deltaE9 mutant presenilin-1. Unlike their transgenic mouse cousins that develop senile plaques but fail to manifest tangles and frank neuronal loss, these transgenic rats-for the first time-develop the full spectrum of Alzheimer pathologies. This makes them an invaluable tool for understanding Alzheimers disease etiology and for testing cutting-edge therapeutics pre-clinically.
Los Angeles, CA 90089
Brain injury, neuroinflammation and Alzheimer's disease.
Breunig JJ, Guillot-Sestier MV, Town T. Front Aging Neurosci. 2013;5:26. doi: 10.3389/fnagi.2013.00026. eCollection 2013. PMID: 23874297
A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aÎ², and frank neuronal loss.
Cohen RM, Rezai-Zadeh K, Weitz TM, Rentsendorj A, Gate D, Spivak I, Bholat Y, Vasilevko V, Glabe CG, Breunig JJ, Rakic P, Davtyan H, Agadjanyan MG, Kepe V, Barrio JR, Bannykh S, Szekely CA, Pechnick RN, Town T. J Neurosci. 2013 Apr 10;33(15):6245-56. doi: 10.1523/JNEUROSCI.3672-12.2013. PMID: 23575824
Innate immunity in Alzheimer's disease: a complex affair.
Guillot-Sestier MV, Town T. CNS Neurol Disord Drug Targets. 2013 Aug;12(5):593-607. PMID: 23574177
Increasing hematopoietic stem cell yield to develop mice with human immune systems. Biancotti JC, Town T. Biomed Res Int. 2013;2013:740892. doi: 10.1155/2013/740892. Epub 2013 Feb 14. PMID: 23509770
Ferulic acid is a nutraceutical Î²-secretase modulator that improves behavioral impairment and alzheimer-like pathology in transgenic mice.
Mori T, Koyama N, Guillot-Sestier MV, Tan J, Town T. PLoS One. 2013;8(2):e55774. doi: 10.1371/journal.pone.0055774. Epub 2013 Feb 8. PMID: 23409038