A5062307843- Alzheimer's disease research and treatments
- Particle accelerators and beam dynamics
- Particle Accelerators and Free-Electron Lasers
- Computational Drug Discovery Methods
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Gyrotron and Vacuum Electronics Research
- Laser-Plasma Interactions and Diagnostics
- Laser-induced spectroscopy and plasma
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Laser Design and Applications
- Laser-Matter Interactions and Applications
- Superconducting Materials and Applications
- RNA Interference and Gene Delivery
- Magnetic confinement fusion research
- Prion Diseases and Protein Misfolding
- Parkinson's Disease Mechanisms and Treatments
- Photocathodes and Microchannel Plates
- Nicotinic Acetylcholine Receptors Study
- HIV Research and Treatment
- Plasma Diagnostics and Applications
- Tryptophan and brain disorders
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
University of California, Irvine
2014-2025
Stony Brook University
2018-2024
Brookhaven National Laboratory
2018-2021
State University of New York
2021
Moscow Engineering Physics Institute
2014
University of California System
2013
Institute on Aging
2003-2009
Thomas Jefferson University
2001
University of Pennsylvania
1998
Abstract Immunization of amyloid precursor protein transgenic mice with fibrillar β-amyloid (Aβ) prevents Alzheimer’s disease (AD)-like neuropathology. The first immunotherapy clinical trial used Aβ, containing the B and T cell self epitopes as immunogen formulated QS21 adjuvant in vaccine. Unfortunately, was halted during phase II stage when 6% participants developed meningoencephalitis. cause meningoencephalitis patients that received vaccine has not been definitively determined; however,...
The Alzheimer's disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in brain. However, attempts at targeting main culprits, neurotoxic Aβ peptides, have thus far proven unsuccessful for improving cognitive function. Recent clinical trials with passively administrated anti-Aβ antibodies failed slow decline mild moderate AD patients, but suggest that an immunotherapeutic approach could be effective patients AD. Using mouse model (Tg2576), we tested...
The advent of chirped-pulse amplification in the 1980s and femtosecond Ti:sapphire lasers 1990s enabled transformative advances intense laser–matter interaction physics. Whereas most experiments have been conducted limited near-infrared range 0.8–1 μm, theories predict that many physical phenomena such as high harmonic generation gases favor long laser wavelengths terms extending high-energy cutoff. Significant progress has made developing few-cycle, carrier-envelope phase-stabilized,...
The development of a safe and effective AD vaccine requires delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed prototype chemokine-based DNA epitope expressing fusion protein that consists 3 copies the self-B cell Abeta(42) (Abeta(1-11)) , non-self helper (PADRE), macrophage-derived chemokine (MDC/CCL22) as...
Active vaccination of elderly Alzheimer's disease (AD) patients with fibrillar amyloid-β peptide (Aβ 42 ), even in the presence a potent Th1 adjuvant, induced generally low titers antibodies small fraction (∼20% responders) those that received AN-1792 vaccine. To improve immunogenicity and reduce likelihood inducing adverse autoreactive T-cells specific for Aβ , we previously tested wild-type mice an alternative approach active immunization: epitope vaccine selectively initiate B cell...
Different strategies proposed as therapy for Alzheimer disease (AD) have aimed to reduce the level of toxic forms A beta peptide in brain. Here, we directly analyze therapeutic utility polyclonal anti-A beta(1-11) antibody induced 3xTg-AD mice vaccinated with second generation prototype epitope vaccine. Substoichiometric concentrations purified prevented aggregation beta(42) and disaggregation preformed fibrils down nonfilamentous nontoxic species. Anti-A delayed oligomer formation but...
Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation monochromatic x-ray free electron lasers, high-brightness hadron beams, or microchip production. In this Letter we report on record-performing superconducting rf gun with ${\mathrm{CsK}}_{2}\mathrm{Sb}$ photocathode. The is generating charge bunches (up $10\text{ }\text{ }\mathrm{nC}/\text{bunch}$) low...
Abstract High brightness, high charge electron beams are critical for a number of advanced accelerator applications. The initial emittance the beam, which is determined by mean transverse energy (MTE) and laser spot size, one most important parameters determining beam quality. bialkali photocathodes illuminated visible have advantages quantum efficiency (QE) low MTE. Furthermore, Superconducting Radio Frequency (SRF) guns can operate in continuous wave (CW) mode at accelerating gradients,...
Abstract Background Clinical trials with passive and active Alzheimer's disease (AD) vaccines suggest that early interventions are needed for improvement of cognitive and/or functional performance in patients, providing impetus the development safe immunologically potent targeting amyloid β (Aβ). The AN‐1792 trial has indicated Aβ‐specific T cells may be unsafe humans; therefore, other based on small Aβ epitopes undergoing preclinical clinical testing. Methods Humoral cellular immune...
Abstract Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation pathological tau correlates with dementia in AD patients. Thus, prevention/inhibition require vaccine/s targeting Aβ and simultaneously or sequentially. Since high antibody titers are required for vaccine efficacy, we have decided to generate vaccines, (AV-1959R), Tau (AV-1980R) Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform evaluate immunogenicity these...
The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late promoting clearing Aβ alone may insufficient to halt disease progression. At same time, pathological tau correlates much better with degree dementia than deposition. Therefore, targeting provide a more promising approach for treatment advanced AD. Recent data demonstrates N-terminal region spanning aa 2-18 termed "phosphatase activation domain"...
Abstract Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses wavelength λ L ~ 1 μ m. Longer- lasers can potentially accelerate higher-quality bunches, since they less power to drive larger wakes in dense plasma. Here, we report on a self-injecting accelerator driven by long-wave-infrared laser: chirped-pulse-amplified CO 2 laser ( ≈ 10 m). Through optical...
We previously demonstrated that our second-generation DNA-based Alzheimer disease (AD) epitope vaccine comprising three copies of a short amyloid-β (Aβ) B cell epitope, Aβ11 fused with the foreign promiscuous Th PADRE (p3Aβ11-PADRE) was immunogenic in mice. However, since DNA vaccines exhibit poor immunogenicity large animals and humans, this study, we sought to improve p3Aβ11-PADRE by modifying express protein 3Aβ11-PADRE free N-terminal aspartic acid eight additional epitopes. Generated...
As a prelude to clinical trials we have characterized B- and T-cell immune responses in macaques AD vaccine candidates: AV-1955 its slightly modified version, AV-1959 (with 3 additional promiscuous Th epitopes).T- B-cell epitope mapping was performed using the ELISPOT assay competition ELISA, respectively.AV-1955 did not stimulate potentially harmful autoreactive T cells, but instead activated broad individualized repertoire of cells specific MultiTEP platform macaques. Although both...
Abstract Background Alzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed hyperphosphorylated tau, which together lead to neurodegeneration cognitive decline. Current therapeutic approaches have primarily aimed reduce pathological aggregates either Aβ or yet phase 3 clinical trials these thus far failed delay progression in humans. Strong preclinical evidence indicates that two abnormally aggregated proteins interact...
Active immunization with fibrillar beta-amyloid peptide (Abeta(42)) as well passive transfer of anti-Abeta antibodies significantly reduces Abeta plaque deposition, neuritic dystrophy, and astrogliosis in the brain mutant amyloid precursor protein (APP)-transgenic mice. Although mechanism(s) clearance from following active or remains to be determined, it is clear that are critical for clearance. DNA provides an attractive alternative direct adjuvant approaches inducing a humoral response...
Abstract Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential avoid adverse responses that occurred during clinical AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy replaces QS21 Th1 type adjuvant used trial a molecular adjuvant, mannan can promote Th2-polarized immune response through interactions mannose-binding and CD35/CD21 receptors of innate system. Previously...