Phone: (352) 273-9689
Fax: (352) 273-5575
Department of Neurology
Room L1-178, McKnight Brain Institute
1149 Newell Drive
Gainesville, FL. 32611
Department of Neurology
University of Florida College of Medicine
HSC Box 100236
Gainesville, FL 32610-0236
Ph.D., Universidad Autonoma de Nuevo Leon, Mexico (1995)
Dr. Rincon-Limas received a bachelor degree on Biopharmaceutical Chemistry from the Autonomous University of Tamaulipas in Reynosa, Mexico. He also obtained a Master’s degree in Microbiology and a summa cum laude Ph.D. degree in Molecular Biology and Genetic Engineering at the Autonomous University of Nuevo Leon in Monterrey, Mexico. He then moved to Baylor College of Medicine in Houston to conduct his postdoctoral training in the Department of Human and Molecular Genetics, where he got training in Developmental Biology and Neurobiology. Later on, he got his first Faculty position in the Department of Neurology and the Mitchell Center for Neurodegenerative Disorders at the University of Texas Medical Branch in Galveston. He moved to the University of Florida in 2010 as an Assistant Professor in the Department of Neurology at the McKnight Brain Institute and is also a member of the UF Genetics Institute and the Center for Translational Research in Neurodegenerative Disease (CTRND).
Selected Honors and Awards
- Fellow, Mexican Ministry of Public Education (SEP)
- Fellow, National Council for Science and Technology of the Mexican Government (CONACYT)
- Medal “Francisco J. Mújica” from the National Institute of Youth, Mexico
- Predoctoral Fellow, International Center for Molecular and Cellular Biology (UNESCO)
- Best Ph.D. Thesis Award, University of Nuevo Leon, Mexico
- PEW Latin American Fellow
- HHMI Start-up Award
Neurodegenerative disorders, including Alzheimer’s, Huntington’s, Parkinson’s and prion diseases, are some of the most dreaded conditions in our society. These conditions affect millions of people worldwide, represent a huge and increasing burden on the health-care system, and constitute one of the major challenges of modern medicine. Unfortunately, the pathogenic mechanisms underlying these debilitating disorders are poorly understood and, therefore, there are no effective therapies to avoid their fatal outcome.
My laboratory focuses on the development and application of new technologies to define the molecular pathways leading to neurodegeneration and to identify potential therapeutic targets. To do so, we utilize the fruit fly Drosophila melanogaster to model molecular, biochemical and pathological aspects of human neurodegenerative conditions. This is achieved by disrupting homologous genes in Drosophila, or by expressing a human disease gene in this organism. Strikingly, the remarkable genetic conservation from flies to humans leads to neurological phenotypes that closely mimic the human disease. Once the model is validated, we apply a multidisciplinary approach combining Drosophila genetics, neuroscience, molecular biology, biochemistry, optogenetics and “omics” technologies. My goal is to use this multidisciplinary effort to generate molecular portraits of these devastating disorders to dissect unknown, fundamental issues in their respective pathologies.
Areas of Research
- Drosophila models of human neurological disorders
- Molecular mechanisms of prion protein misfolding and neurotoxicity
- The role of the ER stress factor XBP1 in neurodegenerative conditions
- Genetic suppressors of amyloid-beta neurotoxicity
- Transcriptome profiling and “omics” technologies in neurodegenerative diseases
- Design and generation of photoactivable transcription factors
Research Strengths and Key Words
Genetic Engineering, Neurobiology, Neuroscience, Developmental Biology, Transcriptional Regulation, Biochemistry, Transgenic Mice, Drosophila Models of Human Diseases, Protein Misfolding Disorders, Mechanisms of Neurodegeneration, Prion Protein, Amyloid Beta, Huntingtin, ER stress, Molecular chaperones.
Selected Peer-Reviewed Publications
- Rincon-Limas DE, Geske RS, Xue J-J, Hsu CY, Overbeek PA, and Patel PI (1994). 5′-flanking sequences of the human HPRT gene direct neuronal expression in the brain of transgenic mice. Journal of Neuroscience Research 38:259-267.
- Rincon-Limas DE, Amaya-Manzanares F, Nino-Rosales ML, and Patel PI (1995). Interplay of ubiquitous and neuronal DNA-binding proteins with a negative regulatory element contributes to the brain-preferential expression of the human HPRT gene. Molecular and Cellular Biology 15:6561-6571.
- Rincon-Limas DE, Lu CH, Canal I, Calleja M, Rodriguez-Esteban C, Izpisua-Belmonte JC, and Botas J (1999). Conservation of the expression and function of apterous orthologues in Drosophila and mammals. Proceedings of the National Academy of Sciences U.S.A. 96: 2165-2170.
- Rincon-Limas DE, Lu C-H, Canal I, and Botas J (200). The level of DLDB/CHIP controls the activity of the LIM-homeodomain protein Apterous: evidence for a functional tetramer complex in vivo. EMBO Journal 19:2602-2614.
- Bergman CM, Barret P, Rincon-Limas DE, Hoskins RA, Gnirke A, Mungall CJ, Wang AM, Kronmiller B, Park S, Stapleton M, George RA, Botas J, Rubin GM, and Celniker SE (2002). Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome. Genome Biology 3: 86-6.
- Branco J, Al-Ramahi I, Ukani L, Pérez AM, Fernandez-Funez P, Rincon-Limas DE, and Botas J (2008). Comparative analysis of genetic modifiers in Drosophila points to common and distinct mechanisms of pathogenesis among polyglutamine diseases. Human Molecular Genetics 17:376-90.
- Fernandez-Funez P, Casas-Tinto S, Gomez-Velazquez M, Cepeda-Nieto AC, Castilla J, Soto C, and Rincon-Limas DE (2009). In vivo generation of neurotoxic prion protein: Role for Hsp70 in accumulation of misfolded isoforms. PLoS Genetics 5:1-14.
- Fernandez-Funez P, Zhang Y, Casas-Tinto S, Xiao X, Zou WQ, and Rincon-Limas DE (2010). Sequence-dependent prion protein misfolding and neurotoxicity. Journal of Biological Chemistry, 285:36897-36908.
- Casas-Tinto S, Zhang Y, Sanchez-Garcia J, Gomez-Velazquez M, Rincon-Limas DE*, and Fernandez-Funez P (2011). The ER stress factor XBP1s prevents amyloid beta neurotoxicity. Human Molecular Genetics 20:2144-2160, * Co-senior author.
- Zou WQ, Xiao X, Yuan J, Ouoti G, Fujioka H, Wang X, Richardson S, Zhou X, Zou R, Li S, Zhu X, McGeer PL, McGeehan J, Kneale G, Rincon-Limas DE, Fernandez-Funez P, Lee HG, Smith MA, Petersen RB, Guo JP (2011). Amyloid beta interacts mainly with insoluble prion protein in the Alzheimer brain. Journal of Biological Chemistry286:15095-15105.
- Rincon-Limas DE, Resendez-Perez D, and Fernandez-Funez P (2009). From fly genetics to human health. CIENCIA UANL 12:83-89 [Spanish].
- Rincon-Limas DE, Casas-Tinto S, and Fernandez-Funez P (2010). Exploring prion protein biology in flies: genetics and beyond. Prion 4:1-8.
- Fernandez-Funez P, Zhang Y, Sanchez-Garcia J, Jensen K, Zou WQ, and Rincon-Limas DE (2011) Pulling rabbits to reveal the secrets of the prion protein. Communicative & Integrative Biology, 4:262-266.
- Rincon-Limas DE, Jensen K, and Fernandez-Funez P (2012). Drosophila models of proteinopathies: the little fly that could. Current Pharmaceutical Design, in press.
Book Chapters and Proceedings
- Fernandez-Funez P, Salinas J, Nino-Rosales L, and Rincon-Limas DE (2008). Novel suppressors of Abeta neurotoxicity. In New Trends in Alzheimer and Parkinson Related Disorders, eds Hanin, I, Windisch M, Poewe W, and Fisher A, 37-41, Medimont Ed., Bologna, Italy.
- Fernandez-Funez P, Malaga-Trillo E, and Rincon-Limas DE (2012). Alternative models of prion diseases. In Prions and Diseases: Volume 2, Pathogenesis and Neuropathology, eds Zou WQ and Gambetti P, Springer, New York, in press.