Yona R Levites

Yona R Levites

Research Associate Professor

Department: MD-NEUROSCIENCE-GENERAL
Business Phone: (352) 273-9660
Business Email: levites.yona@ufl.edu

About Yona R Levites

Dr. Levites is a Research Assistant Professor at the CTRND and department of Neuroscience. She recieved her PhD in the laboratory of Professor Moussa Youdim at the Technion – Israel Institute of Technology, working on the benefits of Green Tea polyphenols in models of Parkinson’s Disease. She continued her training as a postdoctoral fellow in the lab of Professor Todd Golde where she developed recombinant antibody fragments against amyloid beta and their delivery to the CNS via Adeno Associated virus. Currently she continues this path and her primary research is focused on designing, engineering and testing recombinant therapise for neurodegenrative disorders. These diseases are characterized by accumulation of misfolded proteins in the brain, initiating a cascade of neurotoxic and inflammatory events leading eventually to brain organ failure. There are no current therapies against most of these diseases. In the recent years immunotherapeutic approach, specifically targeting misfolded proteins’ accumulation in the CNS has been very promising, although is facing many challenges in clinic. Dr. Levites’ group clones variable regions from many newly developed antibodies against these proteins, modified them to increase their stability and efficacy and further test these novel therapeutics in vitro, cell culture, as well as in various mouse models. The goal of her research is to get preclinical immunotherapy research to the stage where these agents can be evaluated in clinic. Additionally, Dr. Levites plays a key role in developing AAV toolkit, looking for optimal ways to deliver AAV to the CNS and achieve highest levels of gene expression in areas of interest.

Publications

2020
Anti-tau scFvs Targeted to the Cytoplasm or Secretory Pathway Variably Modify Pathology and Neurodegenerative Phenotypes.
Molecular therapy : the journal of the American Society of Gene Therapy. [DOI] 10.1016/j.ymthe.2020.10.007. [PMID] 33128896.
2020
Utilizing minimally purified secreted rAAV for rapid and cost-effective manipulation of gene expression in the CNS.
Molecular neurodegeneration. 15(1) [DOI] 10.1186/s13024-020-00361-z. [PMID] 32122372.
2020
Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.
Cell reports. 32(2) [DOI] 10.1016/j.celrep.2020.107908. [PMID] 32668255.
2020
Aß40 displays amyloidogenic properties in the non-transgenic mouse brain but does not exacerbate Aß42 toxicity in Drosophila.
Alzheimer's research & therapy. 12(1) [DOI] 10.1186/s13195-020-00698-z. [PMID] 33069251.
2020
Diversity in Aβ deposit morphology and secondary proteome insolubility across models of Alzheimer-type amyloidosis.
Acta neuropathologica communications. 8(1) [DOI] 10.1186/s40478-020-00911-y. [PMID] 32252825.
2020
Fyn depletion ameliorates tauP301L-induced neuropathology.
Acta neuropathologica communications. 8(1) [DOI] 10.1186/s40478-020-00979-6. [PMID] 32665013.
2019
An anti-CRF antibody suppresses the HPA axis and reverses stress-induced phenotypes.
The Journal of experimental medicine. 216(11):2479-2491 [DOI] 10.1084/jem.20190430. [PMID] 31467037.
2019
Comparative analyses of the in vivo induction and transmission of α-synuclein pathology in transgenic mice by MSA brain lysate and recombinant α-synuclein fibrils.
Acta neuropathologica communications. 7(1) [DOI] 10.1186/s40478-019-0733-3. [PMID] 31109378.
2019
Intra- and extracellular β-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus.
Scientific reports. 9(1) [DOI] 10.1038/s41598-019-52324-0. [PMID] 31685865.
2019
Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis.
NeuroImage. 202 [DOI] 10.1016/j.neuroimage.2019.116138. [PMID] 31472250.
2019
rAAV-based brain slice culture models of Alzheimer’s and Parkinson’s disease inclusion pathologies.
The Journal of experimental medicine. 216(3):539-555 [DOI] 10.1084/jem.20182184. [PMID] 30770411.
2018
Novel monoclonal antibodies targeting the microtubule-binding domain of human tau.
PloS one. 13(4) [DOI] 10.1371/journal.pone.0195211. [PMID] 29608591.
2018
Short Aβ peptides attenuate Aβ42 toxicity in vivo.
The Journal of experimental medicine. 215(1):283-301 [DOI] 10.1084/jem.20170600. [PMID] 29208777.
2018
Designing antibodies against LRRK2-targeted tau epitopes.
PloS one. 13(9) [DOI] 10.1371/journal.pone.0204367. [PMID] 30261006.
2017
Generation and characterization of new monoclonal antibodies targeting the PHF1 and AT8 epitopes on human tau.
Acta neuropathologica communications. 5(1) [DOI] 10.1186/s40478-017-0458-0. [PMID] 28760159.
2017
Strain-specific Fibril Propagation by an Aβ Dodecamer.
Scientific reports. 7 [DOI] 10.1038/srep40787. [PMID] 28098204.
2016
Deficits in hippocampal-dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis.
Hippocampus. 26(4):455-71 [DOI] 10.1002/hipo.22535. [PMID] 26418152.
2016
Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila.
Proceedings of the National Academy of Sciences of the United States of America. 113(35):E5212-21 [DOI] 10.1073/pnas.1608045113. [PMID] 27531960.
2015
A human monoclonal IgG that binds aβ assemblies and diverse amyloids exhibits anti-amyloid activities in vitro and in vivo.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(16):6265-76 [DOI] 10.1523/JNEUROSCI.5109-14.2015. [PMID] 25904780.
2015
IFN-γ promotes τ phosphorylation without affecting mature tangles.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 29(10):4384-98 [DOI] 10.1096/fj.15-275834. [PMID] 26156074.
2015
Widespread and efficient transduction of spinal cord and brain following neonatal AAV injection and potential disease modifying effect in ALS mice.
Molecular therapy : the journal of the American Society of Gene Therapy. 23(1):53-62 [DOI] 10.1038/mt.2014.180. [PMID] 25228069.
2014
Intracerebroventricular viral injection of the neonatal mouse brain for persistent and widespread neuronal transduction.
Journal of visualized experiments : JoVE. (91) [DOI] 10.3791/51863. [PMID] 25286085.
2013
Capsid serotype and timing of injection determines AAV transduction in the neonatal mice brain.
PloS one. 8(6) [DOI] 10.1371/journal.pone.0067680. [PMID] 23825679.
2013
Robust cytoplasmic accumulation of phosphorylated TDP-43 in transgenic models of tauopathy.
Acta neuropathologica. 126(1):39-50 [DOI] 10.1007/s00401-013-1123-8. [PMID] 23666556.
2013
Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo.
The European journal of neuroscience. 37(8):1203-20 [DOI] 10.1111/ejn.12126. [PMID] 23347239.
2013
Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein.
Acta neuropathologica communications. 1 [DOI] 10.1186/2051-5960-1-38. [PMID] 24252149.
2012
Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo.
Nature communications. 3 [DOI] 10.1038/ncomms2013. [PMID] 22910355.
2012
Bispecific tandem single chain antibody simultaneously inhibits β-secretase and promotes α-secretase processing of AβPP.
Journal of Alzheimer's disease : JAD. 28(4):961-9 [DOI] 10.3233/JAD-2011-111196. [PMID] 22156046.
2012
Overlapping profiles of Aβ peptides in the Alzheimer’s disease and pathological aging brains.
Alzheimer's research & therapy. 4(3) [DOI] 10.1186/alzrt121. [PMID] 22621179.
2011
Inhibiting β-secretase activity in Alzheimer’s disease cell models with single-chain antibodies specifically targeting APP.
Journal of molecular biology. 405(2):436-47 [DOI] 10.1016/j.jmb.2010.10.054. [PMID] 21073877.
2010
Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 24(2):548-59 [DOI] 10.1096/fj.09-141754. [PMID] 19825975.
2009
Generating differentially targeted amyloid-beta specific intrabodies as a passive vaccination strategy for Alzheimer’s disease.
Molecular therapy : the journal of the American Society of Gene Therapy. 17(12):2031-40 [DOI] 10.1038/mt.2009.174. [PMID] 19638957.
2009
Quantitative and mechanistic studies of Abeta immunotherapy.
CNS & neurological disorders drug targets. 8(1):31-49 [PMID] 19275635.
View on: PubMed
2008
BRI2 (ITM2b) inhibits Abeta deposition in vivo.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 28(23):6030-6 [DOI] 10.1523/JNEUROSCI.0891-08.2008. [PMID] 18524908.
2007
Rab5 mediates an amyloid precursor protein signaling pathway that leads to apoptosis.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(27):7141-53 [PMID] 17611268.
View on: PubMed
2006
Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer’s disease mouse models.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 20(14):2576-8 [PMID] 17068112.
View on: PubMed
2006
Interleukin-1 receptor 1 knockout has no effect on amyloid deposition in Tg2576 mice and does not alter efficacy following Abeta immunotherapy.
Journal of neuroinflammation. 3 [PMID] 16872492.
View on: PubMed
2006
Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(46):11923-8 [PMID] 17108166.
View on: PubMed
2006
Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model.
The Journal of clinical investigation. 116(1):193-201 [PMID] 16341263.
View on: PubMed
2003
Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 17(8):952-4 [PMID] 12670874.
View on: PubMed
2003
Neuroprotective strategies in Parkinson’s disease : an update on progress.
CNS drugs. 17(10):729-62 [PMID] 12873156.
View on: PubMed
2002
Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures.
Biochemical pharmacology. 63(1):21-9 [PMID] 11754870.
View on: PubMed
2002
Early and late molecular events in neurodegeneration and neuroprotection in Parkinson’s disease MPTP model as assessed by cDNA microarray; the role of iron.
Neurotoxicity research. 4(7-8):679-689 [PMID] 12709306.
View on: PubMed
2002
Involvement of protein kinase C activation and cell survival/ cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action.
The Journal of biological chemistry. 277(34):30574-80 [PMID] 12058035.
View on: PubMed
2001
Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration.
Journal of neurochemistry. 78(5):1073-82 [PMID] 11553681.
View on: PubMed

Grants

Sep 2020 ACTIVE
A Systems Approach to Targeting Innate Immunity in AD
Role:
Funding: MAYO CLINIC via NATL INST OF HLTH NIA
Aug 2019 ACTIVE
Neuroprotective mechanism of DMF/MMF associated with CAA-related pathology after TBI
Role:
Funding: US ARMY MED RES ACQUISITION
Aug 2019 ACTIVE
Immunotherapy targeting the HPA axis in Alzheimers disease
Role:
Funding: NATL INST OF HLTH NIA
Sep 2018 – Aug 2020
Role of Lipid-derived Oligomer Strains in AD Phenotypes
Role: Principal Investigator
Funding: UNIV OF SOUTHERN MISSISSIPPI via NATL INST OF HLTH NIA
Sep 2018 – Aug 2020
A Systems Approach to Targeting Innate Immunity in AD
Role:
Funding: NATL INST OF HLTH NIA
Feb 2018 – Aug 2020
Periodontal Bacteria augment Progression of Abeta and Tau Pathology
Role:
Funding: FL DEPT OF HLTH ED ETHEL MOORE ALZHEIMER
Aug 2017 – Jul 2020
Periodontal bacteria and Alzheimers disease
Role:
Funding: NATL INST OF HLTH NINDS
Feb 2017 – Mar 2018
Corticotropin-releasing hormone (CRH) Immunotherapy for Alzheimers disease
Role:
Funding: FL DEPT OF HLTH ED ETHEL MOORE ALZHEIMER
Feb 2017 – Sep 2019
Functionalized Intrabodies As Potential anti-Tau Therapy
Role: Principal Investigator
Funding: FL DEPT OF HLTH ED ETHEL MOORE ALZHEIMER
Aug 2015 ACTIVE
University of Florida – Mt. Sinai Medical Center AD Research Center
Role:
Funding: NATL INST OF HLTH NIA
Jul 2014 – Jun 2018
Targeting intracellular and extracellular tau by mono- a
Role: Principal Investigator
Funding: BRIGHTFOCUS FOU
Jul 2013 – Dec 2015
Engineering chaperones for extracellular amyloids
Role: Project Manager
Funding: NATL INST OF HLTH

Education

Postdoctoral training
2002-2008 · Mayo Clinic College of Medicine
PhD
1998-2002 · Technion – Israel Institute of Technology

Teaching Profile

Courses Taught
2018
GMS7980 Research for Doctoral Dissertation
2015
GMS6029 Brain Journal Club

Contact Details

Phones:
Business:
(352) 273-9660
Emails: