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Scott O. Zeitlin

Scott O. Zeitlin

Associate Professor, Neuroscience

Primary Location
PO Box 801392
Primary Phone Number
434.924.5011
Email
[email protected]
Website
https://med.virginia.edu/neuroscience/faculty/primary-faculty/scott-zeitlin-ph-d/zeitlin-lab/

Bio & Overview

My laboratory is interested in understanding the pathogenetic mechanism of Huntington's disease (HD). HD is a dominantly inherited neurodegenerative disorder that affects about 1 in 10,000 people in the United States. In the most common form of the disease, onset occurs between the ages of 30 and 50 with symptoms that include involuntary movement (chorea), cognitive deficits, and dementia. There is no known effective therapy and disease progression over a 10-20 year period ends inevitably in death. The mutation causing HD is an expansion of CAG triplets located near the beginning of the coding region of the IT15 gene. The CAG triplets encode a stretch of polyglutamine that confers a new deleterious function on huntingtin, the protein encoded by the HD gene. Using the mouse as a model system, we are studying the consequences of expressing mutant forms of huntingtin and inactivating HD gene expression in selected tissues at different developmental times. Recently, we have developed conditionally mutant mice that have lost huntingtin expression in the forebrain. These mice exhibit a progressive neurodegenerative phenotype that resembles what is observed in mouse models expressing the mutant form of huntingtin. We are currently investigating the possibility that the HD mutation may also act in a dominant negative fashion, resulting in the loss of huntingtin's normal neuroprotective functions.

Academic Information

Department
Neuroscience
Academic Title
Associate Professor

Primary Education

  • BS, Chemistry, Stanford University, 1979
  • PhD, Genetics and Development, Columbia University, 1985
  • Postdoc, Genetics and Development, Columbia University, 1991

Other Appointments

  • Cell Biology
  • Associate Professor, BMBG
  • Associate Professor, MCDB

Other Affiliations

  • MSTP
  • Associate Professor, BIMS
  • BIMS

Research Interests

Mechanisms of Huntington's Disease Pathogenesis

Research Disciplines

  • Biochemistry
  • Cell and Developmental Biology
  • Neuroscience

Research Opportunities

  • Biochemistry
  • Cell Biology
  • Neuroscience

PhD Programs

  • Cell Biology
  • Neuroscience

Selected Publications

2023

Bragg, R. M., Coffey, S. R., Cantle, J. P., Hu, S., Singh, S., Legg, S. R., . . . Carroll, J. B. (2023). Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.. Life science alliance, 6(11), e202302098. doi:10.26508/lsa.202302098

Bragg, R. M., Coffey, S. R., Cantle, J. P., Hu, S., Singh, S., Legg, S. R. W., . . . Carroll, J. B. (2023). Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.. bioRxiv. doi:10.1101/2023.06.24.546334

2022

Marchionini, D. M., Liu, J. -P., Ambesi-Impiombato, A., Kerker, K., Cirillo, K., Bansal, M., . . . Zeitlin, S. O. (2022). Benefits of global mutant huntingtin lowering diminish over time in a Huntington's disease mouse model. JCI INSIGHT, 7(20). doi:10.1172/jci.insight.161769

Greco, T. M., Secker, C., Ramos, E. S., Federspiel, J. D., Liu, J. -P., Perez, A. M., . . . Cristea, I. M. (2022). Dynamics of huntingtin protein interactions in the striatum identifies candidate modifiers of Huntington disease. CELL SYSTEMS, 13(4), 304-+. doi:10.1016/j.cels.2022.01.005

2021

Braatz, E. M., Andre, E. A., Liu, J. -P., & Zeitlin, S. O. (2021). Characterization of a Knock-In Mouse Model with a Huntingtin Exon 1 Deletion. JOURNAL OF HUNTINGTONS DISEASE, 10(4), 435-454. doi:10.3233/JHD-210494

Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., . . . Tong, C. -K. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). AUTOPHAGY, 17(1), 1-382. doi:10.1080/15548627.2020.1797280

2020

Barnat, M., Capizzi, M., Aparicio, E., Boluda, S., Wennagel, D., Kacher, R., . . . Humbert, S. (2020). Huntington's disease alters human neurodevelopment. SCIENCE, 369(6505), 787-+. doi:10.1126/science.aax3338

2019

Franich, N. R., Hickey, M. A., Zhu, C., Osborne, G. F., Ali, N., Chu, T., . . . Chesselet, M. -F. (2019). Phenotype onset in Huntington's disease knock-in mice is correlated with the incomplete splicing of the mutant huntingtin gene. JOURNAL OF NEUROSCIENCE RESEARCH, 97(12), 1590-1605. doi:10.1002/jnr.24493

2018

Franich, N. R., Basso, M., Andre, E. A., Ochaba, J., Kumar, A., Thein, S., . . . Steffan, J. S. (2018). Striatal Mutant Huntingtin Protein Levels Decline with Age in Homozygous Huntington's Disease Knock-In Mouse Models. JOURNAL OF HUNTINGTONS DISEASE, 7(2), 137-150. doi:10.3233/JHD-170274

2017

Andre, E. A., Braatz, E. M., Liu, J. -P., & Zeitlin, S. O. (2017). Generation and Characterization of Knock-in Mouse Models Expressing Versions of Huntingtin with Either an N17 or a Combined PolyQ and Proline-Rich Region Deletion. JOURNAL OF HUNTINGTONS DISEASE, 6(1), 47-62. doi:10.3233/JHD-160231

Liu, J. -P., & Zeitlin, S. O. (2017). Is Huntingtin Dispensable in the Adult Brain?. JOURNAL OF HUNTINGTONS DISEASE, 6(1), 1-17. doi:10.3233/JHD-170235

2014

Ochaba, J., Lukacsovich, T., Csikos, G., Zheng, S., Margulis, J., Salazar, L., . . . Steffan, J. S. (2014). Potential function for the Huntingtin protein as a scaffold for selective autophagy. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(47), 16889-16894. doi:10.1073/pnas.1420103111

McKinstry, S. U., Karadeniz, Y. B., Worthington, A. K., Hayrapetyan, V. Y., Ozlu, M. I., Serafin-Molina, K., . . . Eroglu, C. (2014). Huntingtin Is Required for Normal Excitatory Synapse Development in Cortical and Striatal Circuits. JOURNAL OF NEUROSCIENCE, 34(28), 9455-9472. doi:10.1523/JNEUROSCI.4699-13.2014

2012

Conforti, P., Camnasio, S., Mutti, C., Valenza, M., Thompson, M., Fossale, E., . . . Cattaneo, E. (2013). Lack of huntingtin promotes neural stem cells differentiation into glial cells while neurons expressing huntingtin with expanded polyglutamine tracts undergo cell death. NEUROBIOLOGY OF DISEASE, 50, 160-170. doi:10.1016/j.nbd.2012.10.015

Zheng, S., Ghitani, N., Blackburn, J. S., Liu, J. -P., & Zeitlin, S. O. (2012). A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin's polyglutamine stretch on CAG140 mouse model pathogenesis. MOLECULAR BRAIN, 5. doi:10.1186/1756-6606-5-28

Fang, C., Bolivar, V. J., Gu, J., Yang, W., Zeitlin, S. O., & Ding, X. (2012). NEUROBEHAVIORAL ABNORMALITIES IN A BRAIN-SPECIFIC NADPH-CYTOCHROME P450 REDUCTASE KNOCKOUT MOUSE MODEL. NEUROSCIENCE, 218, 170-180. doi:10.1016/j.neuroscience.2012.05.027

Culver, B. P., Savas, J. N., Park, S. K., Choi, J. H., Zheng, S., Zeitlin, S. O., . . . Tanese, N. (2012). Proteomic Analysis of Wild-type and Mutant Huntingtin-associated Proteins in Mouse Brains Identifies Unique Interactions and Involvement in Protein Synthesis. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(26), 21599-21614. doi:10.1074/jbc.M112.359307

Ritch, J. J., Valencia, A., Alexander, J., Sapp, E., Gatune, L., Sangrey, G. R., . . . Kegel, K. B. (2012). Multiple phenotypes in Huntington disease mouse neural stem cells. MOLECULAR AND CELLULAR NEUROSCIENCE, 50(1), 70-81. doi:10.1016/j.mcn.2012.03.011

Hickey, M. A., Zhu, C., Medvedeva, V., Lerner, R. P., Patassini, S., Franich, N. R., . . . Chesselet, M. -F. (2012). Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington's disease. MOLECULAR NEURODEGENERATION, 7. doi:10.1186/1750-1326-7-12

Lo Sardo, V., Zuccato, C., Gaudenzi, G., Vitali, B., Ramos, C., Tartari, M., . . . Cattaneo, E. (2012). An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin. NATURE NEUROSCIENCE, 15(5), 713-721. doi:10.1038/nn.3080

Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., . . . Zuckerbraun, B. (2012). Guidelines for the use and interpretation of assays for monitoring autophagy. AUTOPHAGY, 8(4), 445-544. doi:10.4161/auto.19496

Neveklovska, M., Clabough, E. B. D., Steffan, J. S., & Zeitlin, S. O. (2012). Deletion of the Huntingtin Proline-Rich Region does not Significantly Affect Normal Huntingtin Function in Mice. JOURNAL OF HUNTINGTONS DISEASE, 1(1), 71-87. doi:10.3233/JHD-2012-120016

2011

Liu, J. -P., & Zeitlin, S. O. (2011). The long and the short of aberrant ciliogenesis in Huntington disease. JOURNAL OF CLINICAL INVESTIGATION, 121(11), 4237-4241. doi:10.1172/JCI60243

2010

Conroy, J. L., Fang, C., Gu, J., Zeitlin, S. O., Yang, W., Yang, J., . . . Hough, L. B. (2010). Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling. NATURE NEUROSCIENCE, 13(3), 284-286. doi:10.1038/nn.2497

Zheng, S., Clabough, E. B. D., Sarkar, S., Futter, M., Rubinsztein, D. C., & Zeitlin, S. O. (2010). Deletion of the Huntingtin Polyglutamine Stretch Enhances Neuronal Autophagy and Longevity in Mice. PLOS GENETICS, 6(2). doi:10.1371/journal.pgen.1000838