Frank M. LaFerla, PhD
Frank M. LaFerla, Ph.D., is the dean of the UCI School of Biological Sciences and a Chancellor’s Professor in the Department of Neurobiology and Behavior. He joined UCI in 1995 as an assistant professor and later served as chair of Neurobiology and Behavior from 2010 to 2013 and the director of the UCI Institute for Memory Impairments and Neurological Disorders (UCI MIND) from 2009 – 2014 & 2015 – 2018.
Dean LaFerla is the current director of the National Institutes of Health funded UCI Alzheimer’s Disease Research Center and the co-director of the National Institute on Aging funded Model-AD at UCI, a research effort to develop the next generation of model organisms to evaluate and cure Alzheimer’s disease.
His research focuses on understanding the pathogenesis of Alzheimer’s Disease, the most common form of dementia. His scholarly work has had a global influence on the field, as some of the model organisms he has generated to study Alzheimer’s have been distributed to over 150 researchers in more than 20 countries throughout the world. He has published more than 200 original peer-reviewed articles and has been listed among the top 1% cited researchers in his field.
Dean LaFerla has received many honors for his research accomplishments throughout his career, including the Promising Work Award from the Metropolitan Life Foundation for Medical Research, the Ruth Salta Investigator Achievement Award from the American Health Assistance Foundation, the Zenith Fellows Award from the Alzheimer’s Association and the UCI Innovators Award. He is a fellow of the American Association for the Advancement of Science, and an elected member of the American Neurological Association, the American Society for Cell Biology, the International Society for Stem Cell Research and the Society for Neuroscience.
Phone: (949) 824-5315
University of California, Irvine
3400 Biological Sciences III
Irvine, CA 92697
Neurobiology and Behavior
Interdepartmental Neuroscience Program
Institute for Memory Impairments and Neurological Disorders
Center for the Neurobiology of Learning and Memory
Sue and Bill Gross Stem Cell Center
Molecular biology of Alzheimer’s disease and neurodegenerative disorders; Transgenic and Genetically-modified Animal Models, Presenilins and calcium signaling; Learning and memory.
UCI Lauds and Laurels Faculty Distinguished Service Award (2014); California BRAIN Board of Advisors Elected Member (2014); American Neurological Association (2011); Fellow, American Association for the Advancement of Science (2010); UCI Academic Senate Daniel G. Aldrich Jr. Distinguished University Service Award (2010); Chancellor’s Professor (2008); Promising Work Award, MetLife Foundation Awards for Medical Research (2006); UCI Faculty Innovation Award (2005); Zenith Fellow Award, Alzheimer’s Association (2005); Chancellor’s Fellow (2005-2008); Distinguished Mid-career Faculty Award for Research (2005); Ruth Salta Junior Investigator Achievement Award in Alzheimer’s Disease from the American Health Assistance Foundation (2001); Intracellular Imaging Inc. Ratio Imaging Award (1999); Young Scientist Travel Grant –Calgary, Italy (1995); F. M. Firby/Cancer Research Institute Postdoctoral Fellow (1990-93).
Baglietto-Vargas D, Prieto GA, Limon A, Forner S, Rodriguez-Ortiz CJ, Ikemura K, Ager RR, Medeiros R, Trujillo-Estrada L, Martini AC, Kitazawa M, Davila JC, Cotman CW, Gutierrez A, LaFerla FM. (2018). Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer’s disease. Aging Cell. 6:e12791
Van der Jeugd A, Parra-Damas A, Baeta-Corral R, Soto-Faguás CM, Ahmed T, LaFerla FM, Giménez-Llort L, D’Hooge R, Saura CA. (2018). Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice. Sci Rep. 8(1):6431.
Sosna J, Philipp S, Albay R 3rd, Reyes-Ruiz JM, Baglietto-Vargas D, LaFerla FM, Glabe CG. (2018). Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease. Mol Neurodegener. 13(1):11.
Martini AC, Forner S, Trujillo-Estrada L, Baglietto-Vargas D, LaFerla FM. (2018). Past to Future: What Animal Models Have Taught Us About Alzheimer’s Disease. J Alzheimers Dis. 64(s1):S365-S378.
Reidling JC, Relaño-Ginés A, Holley SM, Ochaba J, Moore C, Fury B, Lau A, Tran AH, Yeung S, Salamati D, Zhu C, Hatami A, Cepeda C, Barry JA, Kamdjou T, King A, Coleal-Bergum D, Franich NR, LaFerla FM, Steffan JS, Blurton-Jones M, Meshul CK, Bauer G, Levine MS, Chesselet MF, Thompson LM. (2017). Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington’s Disease Mice. Stem Cell Reports. 2018, 9;10(1):58-72.
Castillo E, Leon J, Mazzei G, Abolhassani N, Haruyama N, Saito T, Saido T, Hokama M, Iwaki T, Ohara T, Ninomiya T, Kiyohara Y, Sakumi K, LaFerla FM, Nakabeppu Y. (2017). Comparative profiling of cortical gene expression in Alzheimer’s disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation. Sci Rep. 7(1):17762.
Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM. (2017). Synaptic Impairment in Alzheimer’s Disease: A Dysregulated Symphony. Trends Neurosci. 40(6):347-357.
Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E, LaFerla FM, Medeiros R. (2016). AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease. Neurodegener Dis. 16(1-2):95-110.
Kim J, Lee S, Choi BR, Yang H, Hwang Y, Park JH, LaFerla FM, Han JS, Lee KW, Kim J. (2016). Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways. Mol. Nutr. Food Res. 61, 2, 2017, 1600194
The neuropathological correlates of Alzheimer’s disease (AD) include amyloid-ß (Aß) plaques and tau-laden neurofibrillary tangles. Although it has been possible to develop transgenic mice that develop one of these lesions, it has proven to be quite challenging to develop mice with both histopathological lesions in the same mouse, in AD-relevant brain regions such as the hippocampus and cortex. To better model AD neuropathology, my lab utilized a novel approach to create a triple transgenic model of AD (3xTg-AD). Rather than crossing independent lines, we microinjected two transgenes (ßAPP and tau) into single-cell embryos from homozygous PS1M146V knockin mice, generating mice with the same genetic background. Compared to crossbreeding, the approach we used offers several major advantages. The integration of the ßAPP and tau transgenes at the same genetic locus renders it unlikely that either transgene will independently assort in subsequent generations. Therefore, this tight linkage coupled to the ‘knockin’ of the PS1 mutation indicates that the 3xTg-AD mice breed as readily as any single transgenic line, particularly because these mice have also been bred to homozygosity. Thus, deriving a large colony is straightforward, cost-effective, and does not require extensive genotyping of the progeny. Moreover, the easy propagation of this transgenic line facilitates their crossing to other transgenic or gene-targeted mice to assess the impact of other genotypes on the neuropathological or physiological phenotype. Lastly, another advantage to this approach is that multiple transgenes are introduced into an animal without altering or mixing the background genetic constitution. Thus, an important confounding variable is avoided, which may be a crucial parameter for behavioral, electrophysiological, and vaccine-based experiments
The 3xTg-AD mice develop both plaque and tangle pathology in AD-relevant brain regions. The 3xTg-AD mice develop extracellular Aß deposits prior to tangle formation, consistent with the amyloid cascade hypothesis. Despite equivalent overexpression of the human ßAPP and human tau transgenes, Aß deposition develops prior to the tangle pathology, consistent with the amyloid cascade hypothesis. In addition, these mice exhibit deficits in synaptic plasticity, including long-term potentiation (LTP) that occurs prior to extracellular Aß deposition and tau pathology, but is associated with intracellular Aß immunoreactivity. These studies support the view that synaptic dysfunction is a proximal defect in the pathobiology of AD, preceding extracellular plaque formation and neurofibrillary pathology. As these 3xTg-AD mice phenocopy critical aspects of AD neuropathology, this model will be useful in pre-clinical intervention trials, particularly because the efficacy of anti-AD compounds in mitigating the neurodegenerative effects mediated by both signature lesions can be evaluated.
American Association for Advancement of Science
American Neurological Association
American Society for Cell Biology
International Society for Stem Cell Research
Society for Neuroscience
A Messsage From the Dean
Learn more about Dean LaFerla, his vision for the School of Biological Sciences, and how the School is training the next generation of Biologists.