A5058073147- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- Nerve injury and regeneration
- Tissue Engineering and Regenerative Medicine
- Viral gastroenteritis research and epidemiology
- Animal Genetics and Reproduction
- Cholinesterase and Neurodegenerative Diseases
- Tryptophan and brain disorders
- Protein purification and stability
- Computational Drug Discovery Methods
- Parkinson's Disease Mechanisms and Treatments
- Insect Resistance and Genetics
- Innovative Microfluidic and Catalytic Techniques Innovation
- 3D Printing in Biomedical Research
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Fluid Dynamics and Mixing
- Protease and Inhibitor Mechanisms
- Genetic Neurodegenerative Diseases
- CAR-T cell therapy research
University of Florida
2014-2025
Universidad de Los Andes, Chile
2025
Instituto Português de Oncologia Francisco Gentil
2023-2024
Universidad de Los Andes
2024
ECBio (Portugal)
2008-2023
The University of Texas Southwestern Medical Center
2023
Dallas VA Medical Center
2023
National Human Genome Research Institute
2013-2023
University of Lisbon
2022
WinnMed
2020
Rationale: There is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by destruction. The association of α1-antitrypsin deficiency with the development has supported concept protease/antiprotease imbalance mediates cigarette smoke–induced emphysema.Objectives: We propose that, addition to its antielastolytic effects, may have broader biological effects lung, preventing through inhibition cells...
Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition spinal cord glia and glial pro-inflammatory cytokines as important contributors to suggests an alternative therapeutic strategy; that is, targeting activation or its downstream consequences. While several glial-selective drugs have been successful in controlling animal models, none are optimal human use. Thus the aim present studies was explore a novel approach pain....
Neuropathic pain is a major clinical problem unresolved by available therapeutics. Spinal cord glia play pivotal role in neuropathic pain, via the release of proinflammatory cytokines. Anti-inflammatory cytokines, like interleukin-10 (IL-10), suppress Thus, IL-10 may provide means for controlling glial amplification pain. We recently documented that intrathecal protein resolves albeit briefly (approximately 2-3 h), given its short half-life. Intrathecal gene therapy using viruses encoding...
The secretion of trophic factors by mesenchymal stromal cells has gained increased interest given the benefits it may bring to treatment a variety traumatic injuries such as skin wounds. Herein, we report on three-dimensional culture-based method improve paracrine activity specific population umbilical cord tissue-derived (UCX®) towards application conditioned medium for cutaneous wounds.A UCX® culture model was developed and characterized with respect spheroid formation, cell phenotype...
Adeno-associated virus (AAV) mediated gene expression is a powerful tool for therapy and preclinical studies. A comprehensive analysis of CNS cell type tropism, levels biodistribution different capsid serotypes has not yet been undertaken in neonatal rodents. Our previous studies show that intracerebroventricular injection with AAV2/1 on day P0 results widespread but the limited if injected beyond P1. To extend these observations we explored effect timing tropism six commonly used...
Recent Genome Wide Association Studies (GWAS) have identified novel rare coding variants in immune genes associated with late onset Alzheimer's disease (LOAD). Amongst these, a polymorphism phospholipase C-gamma 2 (PLCG2) P522R has been reported to be protective against LOAD. PLC enzymes are key elements signal transmission networks and potentially druggable targets. PLCG2 is highly expressed the hematopoietic system. Hypermorphic mutations humans cause autoinflammation disorders, suggesting...
Abstract Introduction Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal (MSCs) have been granted considerable interest. However, whereas beneficial effects bone marrow MSCs (BM-MSCs) in context diseased heart are widely reported, data still scarce on from umbilical cord matrix (UCM-MSCs). Herein we report effect UCM-MSC transplantation infarcted murine heart, seconded by dissection molecular mechanisms at play. Methods Human...
Research Article19 October 2018Open Access Source DataTransparent process High-affinity interactions and signal transduction between Aβ oligomers TREM2 Christian B Lessard Center for Translational in Neurodegenerative Disease, Department of Neuroscience, University Florida, Gainesville, FL, USA Search more papers by this author Samuel L Malnik Yingyue Zhou Pathology Immunology, Washington School Medicine, St. Louis, MO, Thomas Ladd Pedro E Cruz Yong Ran orcid.org/0000-0002-9748-4392 Mahan...
Recombinant adeno-associated viruses (rAAV) have been widely used in gene therapy applications for central nervous system diseases. Though rAAV can efficiently target neurons and astrocytes mouse brains, microglia, the immune cells of brain, are refractile to rAAV. To identify AAV capsids with microglia-specific transduction properties, we initially screened most commonly serotypes, AAV1-9 rh10, on primary microglia cultures. While these were not permissive, then tested microglial targeting...
MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived (BM-MSCs), gold-standard in immunotherapy. Immunogenicity immunosuppression assessed by mixed lymphocyte reactions, suppression of proliferation induction regulatory T cells. Results showed that UCX less immunogenic higher activity than BM-MSCs. Further, did not need prior activation or priming exert effects. This was further corroborated vivo a...
Rheumatoid arthritis (RA) is an autoimmune disorder whose treatment mostly restricted to pain and symptom management the delay of joint destruction. Mesenchymal stem/stromal cells from umbilical cord tissue (UC-MSCs) have previously been proven be immunomodulatory more efficient than bone marrow-derived MSCs in causing remission local systemic arthritic manifestations vivo. Given paracrine nature UC-MSC activity, their application as active substances can replaced by secretome, thus avoiding...
IL-10 is a pluripotent cytokine that plays pivotal role in the regulation of immune and inflammatory responses. Whereas short-term administration has shown benefit acute glomerulonephritis, no studies have addressed potential benefits chronic renal disease. Chronically elevated blood levels rats were achieved by recombinant adeno-associated virus serotype 1 (rAAV1-IL-10) vector. Control given similar dose rAAV1-GFP. Four weeks after injection, serum measured ELISA, disease was induced 5/6...
Lentiviral vectors (LVs) hold great potential as gene delivery vehicles. However, the manufacturing and purification of these still present major challenges, mainly because low stability virus, essentially due to fragility membrane envelope. The main goal this work was establishment a fast, scalable, robust downstream protocol for LVs, combining microfiltration, anion-exchange, ultrafiltration technologies toward maximization infectious LVs recovery. CIM® (Convective Interaction Media)...
Processing of amyloid-β (Aβ) precursor protein (APP) by γ-secretase produces multiple species Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer (Aβ42–43). γ-Secretase modulators, a class Alzheimer’s disease therapeutics, reduce production the pathogenic Aβ42 but increase relative abundance peptides. To evaluate pathological relevance these peptides, we expressed Aβ36–40 Aβ42–43 in Drosophila melanogaster to inherent toxicity potential modulatory effects on toxicity. In contrast Aβ42, were...
There is considerable interest in harnessing innate immunity to treat Alzheimer's disease (AD). Here, we explore whether a decoy receptor strategy using the ectodomain of select TLRs has therapeutic potential AD. AAV-mediated expression human TLR5 (sTLR5) alone or fused IgG4 Fc (sTLR5Fc) results robust attenuation amyloid β (Aβ) accumulation mouse model Alzheimer-type Aβ pathology. sTLR5Fc binds oligomeric and fibrillar with high affinity, forms complexes Aβ, blocks toxicity. Oligomeric...
Interleukin 10 (IL-10) is a pleiotropic cytokine with well known antiinflammatory, immunosuppressive, and immunostimulatory properties. Chronic allograft rejection, characterized by vascular neointimal proliferation, major cause of organ transplant loss, particularly in heart kidney recipients. In Dark Agouti to Lewis rat model aortic transplantation, we evaluated the effects single intramuscular injection recombinant adeno-associated viral vector (serotype 1) encoding IL-10 (rAAV1-IL-10) on...
Aldosterone increases renal tubular Na+ absorption in large part by increasing transcription of the epithelial channel α-subunit (α-ENaC) expressed apical membrane collecting duct principal cells. We recently reported that a complex containing histone H3K79 methyltransferase disruptor telomeric silencing-1 (Dot1) associates with and represses α-ENaC promoter mouse inner medullary mIMCD3 cells, aldosterone acts to disrupt this its inhibitory effects (Zhang, W., Xia, X., Reisenauer, M. R.,...
Genetic studies have established a causative role for α-synuclein (αS) in Parkinson's disease (PD), and the presence of αS aggregates form Lewy body (LB) neurite (LN) protein inclusions are defining pathological features PD. Recent data has that extracellular can induce intracellular pathologies supporting hypothesis pathology spread via "prion-like" self-templating mechanism.Here we investigated potential conformational templating by seeding using recombinant wild-type PD-linked mutant...
Standardization of mesenchymal stromal cells (MSCs) manufacturing is urgently needed to enable translational activities and ultimately facilitate comparison clinical trial results. In this work we describe the adaptation a proprietary method for isolation specific umbilical cord tissue-derived population MSCs, herein designated by its registered trademark as UCX®, towards production an advanced therapy medicinal product (ATMP). The focused on different stages production, from cell steps...
UBQLN2 mutations have recently been associated with familial forms of amyotrophic lateral sclerosis (ALS) and ALS-dementia. encodes for ubiquilin-2, a member the ubiquitin-like protein family which facilitates delivery ubiquitinated proteins to proteasome degradation. To study potential role ubiquilin-2 in ALS, we used recombinant adeno-associated viral (rAAV) vectors express three identified ALS-linked mutants (P497H, P497S, P506T) primary neuroglial cultures developing neonatal mouse...
The architecture of the spinal cord makes efficient delivery recombinant adeno-associated virus (rAAV) vectors throughout neuraxis challenging. We describe a paradigm in which small amounts delivered intraspinally to newborn mice result robust rAAV-mediated transgene expression cord. compared efficacy rAAV2/1, 2/5, 2/8, and 2/9 encoding EGFP hindlimb muscle (IM), cisterna magna (ICM), or lumbar (IS) neonatal pups. IS injection all four capsids resulted transduction with rAAV2/5, appearing be...