- Alzheimer's disease research and treatments
- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Prion Diseases and Protein Misfolding
- Virus-based gene therapy research
- CAR-T cell therapy research
- Hedgehog Signaling Pathway Studies
- CRISPR and Genetic Engineering
- interferon and immune responses
- Immunotherapy and Immune Responses
- Genetic and Kidney Cyst Diseases
- Sirtuins and Resveratrol in Medicine
- Connexins and lens biology
- vaccines and immunoinformatics approaches
- Influenza Virus Research Studies
- RNA Interference and Gene Delivery
- Cerebrovascular and Carotid Artery Diseases
- Hormonal Regulation and Hypertension
- Adrenal Hormones and Disorders
- Biochemical effects in animals
- RNA regulation and disease
- Dementia and Cognitive Impairment Research
- Endoplasmic Reticulum Stress and Disease
- Neurological Disorders and Treatments
- Histone Deacetylase Inhibitors Research
Emory University
2023-2024
University of Florida
2014-2022
Allen Institute for Brain Science
2014-2019
Florida College
2014-2019
Institute for Neurodegenerative Disorders
2019
Instituto Cajal
2016
Universidad Complutense de Madrid
2016
Universitat Autònoma de Barcelona
2016
United Arab Emirates University
2016
Instituto de Química Orgánica General
2016
The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed connexins. Previous reports have suggested that junctions are suppressive based on connexin 43 (Cx43), but this does not take into account differences in connexin-mediated ion selectivity intercellular rate drive diversity. We find glioblastoma cancer stem (CSCs) possess functional can be targeted using...
Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal synaptic physiology by responding to neurotransmitters with Ca2+ elevations releasing gliotransmitters that activate receptors. Aging involves astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence the astrocyte-neuron signaling is derived from studies young animals; however, features adult aging remain largely unknown. We have investigated...
Abstract There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is difficult due dose-limiting toxicities, blood-brain-barrier, and suppressive tumor microenvironment. Glioblastoma notoriously devoid of lymphocytes driven in part a paucity lymphocyte trafficking factors necessary prompt their recruitment...
// Lan B. Hoang-Minh 1, 3 , Loic P. Deleyrolle 2, Dorit Siebzehnrubl 1 George Ugartemendia Hunter Futch 2 Benjamin Griffith Joshua J. Breunig 5- 9 Gabriel De Leon 4 Duane A. Mitchell 3, Susan Semple-Rowland Brent Reynolds Matthew R. Sarkisian Department of Neuroscience, University Florida College Medicine, McKnight Brain Institute, Gainesville, Florida, USA Neurosurgery, Preston Wells, Jr. Center for Tumor Therapy, UF Immunotherapy Program, 5 Cedars-Sinai Regenerative Medicine Cedar-Sinai...
The heterogeneity of Alzheimer disease requires the development multitarget drugs for treating symptoms and its progression. Both cholinergic monoamine oxidase dysfunctions are involved in pathological process. Thus, we hypothesized that therapies focused on these targets might be effective. We have developed assessed a new product, coded ASS234, multipotent acetyl butyrylcholinesterase/monoamine A-B inhibitor with potent inhibitory effect amyloid-β aggregation as well antioxidant...
BACKGROUNDObesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge assessed the impact obesity genetics on 23-valent (PPSV23) efficacy. We relationship (primary analysis) stimulator interferon genes (STING1) genotype (secondary PPSV23 efficacy.METHODSNonobese (BMI 22-25 kg/m2) obese participants ≥30 were given a single dose PPSV23. Blood was drawn immediately prior 4-6 weeks after vaccination....
Abstract Background Recombinant adeno-associated virus (rAAV) is widely used in the neuroscience field to manipulate gene expression nervous system. However, a limitation use of rAAV vectors time and expense needed produce them. To overcome this limitation, we evaluated whether unpurified secreted into media following scalable PEI transfection HEK293T cells can be lieu purified rAAV. Methods We packaged rAAV2-EGFP 30 different wild-type mutant capsids subsequently collected containing...
Hypothalamic–pituitary–adrenal (HPA) axis dysfunction contributes to numerous human diseases and disorders. We developed a high-affinity monoclonal antibody, CTRND05, targeting corticotropin-releasing factor (CRF). In mice, CTRND05 blocks stress-induced corticosterone increases, counteracts effects of chronic variable stress, induces other phenotypes consistent with suppression the HPA axis. skeletal muscle hypertrophy increases lean body mass, not previously reported small-molecule...
Seeding of pathology related to Alzheimer's disease (AD) and Lewy body (LBD) by tissue homogenates or purified protein aggregates in various model systems has revealed prion-like properties these disorders. Typically, are injected into adult mice stereotaxically. Injection brain lysates newborn represents an alternative approach delivering seeds that could direct the evolution amyloid-β (Aβ) co-mixed with either tau α-synuclein (αSyn) susceptible mouse models.Homogenates human pre-frontal...
<title>Abstract</title> The promise of immunotherapy to induce long-term durable responses in conventionally treatment resistant tumors like glioblastoma (GBM) has given hope for patients with a dismal prognosis. Yet, few have demonstrated significant survival benefit despite multiple clinical trials designed invigorate immune recognition and tumor eradication. Insights gathered over the last two decades revealed numerous mechanisms by which glioma cells resist conventional therapy evade...
Application of toxic compounds used at maximum tolerated dose until resistance develops is the most commonly experienced outcome in cancer therapy. Based on successful concepts borrowed from field ecology to manage pest populations, we developed a therapeutic strategy relying use multiple independent and non-toxic stressors that enable efficient horizontal vertical targeting tumor. Our treatment (CA.001) uses combination two distinct approaches. The first aspect our approach involves...
Abstract Adults diagnosed with glioblastoma multiforme (GBM) typically have a median survival less than 15 months. GBM patient biopsies and derived cell lines contain subsets of cells extending primary cilia, microtubular antennae that mediate signaling events reported to influence proliferation tumor growth. However, it remains unclear how cilia contribute the phenotypic characteristics GBM. To determine whether progression, we generated several stable patient-derived devoid by expressing...
The coordination of complex tumor processes requires cells to rapidly modify their phenotypes using direct cell-cell communication through gap junction channels composed connexins. Previous reports suggest that junctions are suppressors based on connexin 43 (Cx43), but this hypothesis fails consider the differences in connexin-mediated intercellular rate and ion selectivity drive diversity. Using patient-derived specimens, we screened proteins found glioblastoma cancer stem (CSCs) expressed...
Epidemiologic and biomarker studies have posited an association between the experience of chronic psychologic stress increased incidence Alzheimer's Disease (AD). Corticotropin-releasing hormone (CRH) cortisol are two main mediators response to in humans, both CRH been found exacerbate amyloid ß deposition tau phosphorylation relevant mouse models. As AD patients frequent comorbid behavioral psychiatric dysfunctions including agitation depression, signaling pathways may provide therapeutic...
Glioblastoma represents the most common and deadly type of brain tumor in adults. Although it is widely recognized that combinatorial therapeutic approaches may be necessary to achieve lasting remission or cure, identification novel therapies challenging. Despite availability a number potent intuitively combined biologic monotherapies, cost performing studies using multiple agents prohibitive, delivery therapeutics within often difficult. Recombinant Adeno Associated Viral (rAAV) vectors...
Hypothalamic-pituitary-adrenal (HPA) axis dysfunction contributes to numerous human diseases and disorders. We developed a high affinity, ~1 pM Kd, monoclonal antibody (CTRND05) targeting corticotropin-releasing factor (CRF). In mice, CTRND05 blocks stress-induced corticosterone increases, counteracts effects of chronic variable stress, induces other phenotypes consistent with suppression the HPA axis. skeletal muscle hypertrophy increases in lean body mass, not previously reported...
Abstract Background Pathological aging (PA) patients are individuals that cognitively normal prior to death but have abundant and widespread amyloid‐β (Aβ) deposits. These typically few cored amyloid deposits with variable levels of diffuse parenchymal and/or vascular There is little or no inflammatory reaction, neuritic pathology neurofibrillary tangles in the cortex. Previously, we shown total Aβ PA brain lysates were similar Alzheimer’s disease (AD) lysates, overlap length peptides...
Abstract Background Seeding of pathology related to Alzheimer’s disease (AD) and Lewy body (LBD) by the injection tissue homogenates, purified proteins, or recombinant proteins into model systems has revealed prion-like seeding protein aggregates that define these disorders. Most commonly homogenates are injected adult mice stereotaxically. Injection brain lysates newborn represents an alternative approach delivering seeds could be used direct evolution amyloid-β (Aβ) co-mixed with either...