A5079445710- Organ Transplantation Techniques and Outcomes
- RNA Interference and Gene Delivery
- Organ Donation and Transplantation
- RNA Research and Splicing
- Liver Disease and Transplantation
- Genetic Neurodegenerative Diseases
- Advanced biosensing and bioanalysis techniques
- Lung Cancer Treatments and Mutations
- Transplantation: Methods and Outcomes
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- HIV Research and Treatment
- Xenotransplantation and immune response
- Cardiovascular and Diving-Related Complications
- Renal Transplantation Outcomes and Treatments
- Abdominal Trauma and Injuries
- Aortic Disease and Treatment Approaches
- Immune Cell Function and Interaction
- Congenital Anomalies and Fetal Surgery
- Nanoparticle-Based Drug Delivery
- Multiple and Secondary Primary Cancers
- MicroRNA in disease regulation
- Agriculture, Plant Science, Crop Management
- Ancient and Medieval Archaeology Studies
- Electrospun Nanofibers in Biomedical Applications
University of Massachusetts Chan Medical School
2020-2024
National Institute of Allergy and Infectious Diseases
2023-2024
National Institutes of Health
2023-2024
UMass Memorial Medical Center
2020
Worcester Memorial Hospital
2020
University of Pittsburgh
2015
Huntington's disease (HD) is a severe neurodegenerative disorder caused by the expansion of CAG trinucleotide repeat tract in huntingtin gene. Inheritance expanded repeats needed for HD manifestation, but further somatic non-dividing cells, particularly striatal neurons, hastens onset. Called expansion, this process mediated mismatch repair (MMR) pathway. Among MMR components identified as modifiers onset, MutS homolog 3 (MSH3) has emerged potentially safe and effective target therapeutic...
Abstract INTRODUCTION The most significant genetic risk factor for late‐onset Alzheimer's disease (AD) is APOE4 , with evidence gain‐ and loss‐of‐function mechanisms. A clinical need remains therapeutically relevant tools that potently modulate APOE expression. METHODS We optimized small interfering RNAs (di‐siRNA, GalNAc) to silence brain or liver Apoe evaluated the impact of each pool on pathology. RESULTS In adult 5xFAD mice, siRNAs targeting CNS efficiently silenced expression reduced...
While an increasing number of siRNA therapies are reaching the market, challenge efficient extra-hepatic delivery continues to limit their full therapeutic potential. Drug vehicles and hydrophobic conjugates being employed overcome bottleneck. Previously, we reported a novel dendritic conjugate that can be appended efficiently oligonucleotides, allowing them bind albumin with nanomolar affinity. Here, explore ability this albumin-binding improve siRNAs in vivo. We demonstrate binds...
HIV-1 gp120 glycan binding to C-type lectin adhesion receptor L-selectin/CD62L on CD4 T cells facilitates viral attachment and entry. Paradoxically, the impedes budding from infected release requires shedding of CD62L. To systematically investigate CD62L-shedding mediated its potential inhibition, we screened compounds specific for serine-, cysteine-, aspartyl-, Zn-dependent proteases CD62L inhibition found that a subclass Zn-metalloproteinase inhibitors, including BB-94, TAPI, prinomastat,...
Small interfering RNA (siRNAs) hold immense promise for treating cardiac and muscular diseases, but robust scalable delivery to these tissues remains a challenge. Recent advances in strategies muscle include conjugation of biologics (antibody/antibody fragments, peptides), which are currently clinical development. However, the manufacturing biologic-siRNA conjugates is challenging complex process. By contrast, lipophilic siRNAs readily chemically synthesized at scale support sufficient...
HIV infection remains incurable to date and there are no compounds targeted at the viral release. We show here release is not spontaneous, rather requires caspases activation shedding of its adhesion receptor, CD62L. Blocking caused virion tethering by CD62L deficient viruses. Not only productive experimental infections require for release, from both viremic aviremic patient-derived CD4 T cells also caspase activation, suggesting cellular reservoirs depends on apoptotic receptor. Further...
Introduction: Bicuspid aortic valve (BAV) is associated with an aortopathy that manifests as a dilatation of the proximal ascending aorta. The mechanisms aneurysm formation in BAV patients are not completely understood. Our group established medial smooth muscle cells (SMC) from aneurysmal exhibit weakened oxidative stress defense. Hypothesis: defense SMCs leads to elevated aorta and decreases SMC viability. Methods: Aortic specimens were harvested undergoing and/or replacement due aneurysm,...
Abstract The most common genetic risk factor for late-onset Alzheimer’s disease (AD) is the APOE4 allele, with evidence gain- and loss-of-function mechanisms. ApoE knockout in mice abrogates AD phenotypes but causes severe atherosclerosis due to role of liver cholesterol homeostasis. Previous attempts inhibit brain-specific anti-sense oligonucleotides only modestly reduced expression had no effect on amyloid burden adult mice. Here, we optimized a divalent small interfering RNA (di-siRNA)...
Abstract Huntington’s Disease (HD) is a severe neurodegenerative disorder caused by expansion of the CAG trinucleotide repeat tract in huntingtin gene. Inheritance expanded repeats needed for HD manifestation, but further somatic non-dividing cells, particularly striatal neurons, hastens disease onset. Called expansion, this process mediated mismatch repair (MMR) pathway. Among MMR components identified as modifiers onset, MutS Homolog 3 (MSH3) has emerged potentially safe and effective...