A5056435509- HIV Research and Treatment
- Retinoids in leukemia and cellular processes
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- interferon and immune responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Endoplasmic Reticulum Stress and Disease
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Estrogen and related hormone effects
- Hematopoietic Stem Cell Transplantation
- Mosquito-borne diseases and control
- Genetics and Neurodevelopmental Disorders
- Cytomegalovirus and herpesvirus research
- Synthesis and biological activity
- Cell death mechanisms and regulation
- Prion Diseases and Protein Misfolding
- Lymphoma Diagnosis and Treatment
- Bipolar Disorder and Treatment
- CAR-T cell therapy research
- Heat shock proteins research
- Multiple Myeloma Research and Treatments
University of Pennsylvania
2013-2024
California University of Pennsylvania
2022
The University of Texas Health Science Center at San Antonio
2003-2007
The University of Texas Health Science Center at Houston
2007
HIV-associated neurocognitive disorder (HAND), characterized by a wide spectrum of behavioral, cognitive, and motor dysfunctions, continues to affect approximately 50 % HIV(+) patients despite the success combination antiretroviral drug therapy (cART) in periphery. Of note, potential toxicity drugs central nervous system (CNS) remains remarkably underexplored may contribute persistence HAND cART era. Previous studies have shown antiretrovirals (ARVs) be neurotoxic peripheral vivo neurons...
Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies antiretroviral-treated patients revealed persistent white matter abnormalities including diffuse myelin pallor, diminished tracts, and decreased protein mRNAs. Loss can contribute to dysfunction because the membrane generated by oligodendrocytes is essential for rapid signal transduction axonal...
The prevalence of HIV‐associated neurocognitive impairment (NCI), which includes dementia (HAD) and minor cognitive motor disorder (MCMD), has been increasing. HIV‐infected and/or activated macrophages/microglia in the brain initiate neurodegeneration seen NCI via soluble neurotoxic mediators, including reactive oxygen species, viral proteins excitotoxins. Neurotoxic factors released by injure neurones directly alter astrocytic homeostatic functions, can lead to excitotoxicity oxidative...
Adhesion molecules and stromal cell‐derived factor‐1 (SDF‐1)/CXCR4 signaling play key roles in homing mobilization of hematopoietic stem cells (HSC). Active through SDF‐1/CXCR4 upregulation adhesion are required for homing, whereas downregulation disruption HSC. We studied the surface expression CXCR4 very late activation antigen (VLA)‐4 VLA‐5 on myeloma mobilized with cyclophosphamide GM‐CSF 12 multiple patients undergoing HSC autologous transplantation. also plasma levels SDF‐1 apheresis...
Abstract Although the specific mechanism of neuronal damage in human immunodeficiency virus (HIV) ‐associated dementia is not known, a prominent role for NMDA receptor (NMDAR)‐induced excitotoxicity has been demonstrated neurons exposed to HIV‐infected/activated macrophages. We hypothesized NMDAR‐mediated activation calcium‐dependent protease, calpain, would contribute cell death by induction cyclin‐dependent kinase 5 (CDK5) activity. Using an vitro model HIV neurotoxicity, which primary rat...
Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), severe motor/cognitive disorder afflicting HIV(+) patients. However, prevalence subtler forms neurocognitive dysfunction, which together with HAD are termed disorders (HAND), continues escalate post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic neuronal loss observed autopsy cases suggest an underlying neuroinflammatory process, due neurotoxic factors...
HIV-associated neurocognitive disorders (HANDs) share common symptoms with Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Plaques are formed aggregation of Aβ oligomers, may be the toxic species in AD pathogenesis, and oligomers generated cleavage amyloid precursor protein (APP) β-site cleaving enzyme 1 (BACE1). BACE1 inhibitors reverse neuronal loss cognitive decline animal models AD. Although studies have also found evidence altered APP processing HIV+...
AMD3100 is a drug capable of mobilizing peripheral blood stem cells (PBSCs) in donors and cancer patients as single agent or combination with granulocyte-colony-stimulating factor (G-CSF). We initiated phase II study 11 refractory relapsed non-Hodgkin's lymphoma (NHL) patients, receiving 16 microg/kg daily G-CSF for 4 days followed by 240 given subcutaneously on new schedule 9-10 h before apheresis collection day 5. Our aims were to assess the effect mobilization CD34+ cells, dendritic (DCs)...
Despite combined antiretroviral therapy (cART), HIV-associated neurocognitive disorder (HAND) affects 30-50% of HIV-positive patients. Importantly, persistent white matter pathologies, specifically corpus callosum thinning and disruption microstructures observed in patients with HAND despite viral control through cART, raise the possibility that HIV infection setting suboptimal cART may perturb oligodendrocyte (OL) maturation, function and/or survival, influencing persistence era. To examine...
Mutations in p53 are the most common genetic abnormality cancers. Arsenic trioxide (ATO) is an effective chemotherapeutic agent for treatment of acute promyelocytic leukemia (APL) and being tested phase II studies various types We have shown that ATO a potent inducer apoptosis multiple myeloma cells, engaging primarily intrinsic apoptotic pathway cells expressing w.t. extrinsic mutant p53. To further establish differential signals relation to functional status we studied activation pathways...
Arsenic trioxide (ATO) is effective in the treatment of acute promyelocytic leukemia (APL) and induces apoptosis APL cells a great variety other cancer cells. We have previously shown that ATO myeloma two different modes depending on p53 status In expressing mutated p53, induced, G2/M arrest activation caspase 8 3 rapid extensive apoptosis. Myeloma w.t. induced G1 delayed with 9 3. APO2/TRAIL receptor expression was both cell types synergized induction Here we tested effect mitochondrial...
AbstractArsenic trioxide (ATO) and paclitaxel (TAXOL) are effective in the treatment of various types cancers. Both drugs induce G2/M arrest. We have previously shown that ATO is a potent inducer apoptosis myeloma cells expressing mutant p53 engaging both intrinsic extrinsic apoptotic pathways. Here we compared effect TAXOL on varying levels Bcl-2. rapidly induced Apo2/TRAIL, activation caspase 8, cleavage BID, depolarization mitochondrial membrane (MM) release AIF from mitochondria Bcl-2...
Dendritic cells (DCs) are the most efficient antigen-presenting and play a role in immune reconstitution after autologous transplantation. Recent reports suggest that mobilization with granulocyte colony-stimulating factor (G-CSF) containing regimens polarizes DCs into pDC2, which could potentially result increased Th2 response decreased graft-versus-host disease (GVHD) allogeneic transplantation cytotoxic Th1 graft versus tumor effect, translate relapse rate. Previously, we have shown...
Dendritic cells (DCs) are effective antigen‐presenting cells. We hypothesized that increasing the DC populations in donor lymphocyte infusions (DLIs) may augment graft versus malignancy effect, particularly if granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) mobilization resulted increased precursor dendritic cell (pDC) 1 Mature DCs, pDC1 cells, pDC2 and CD34+ from same were compared after granulocyte (G‐CSF) mobilized peripheral blood stem collections GM‐CSF DLI collections....
Based on emerging evidence the role for specific single-nucleotide variants (SNVs) in EIF2AK3 encoding integrated stress response kinase PERK, neurodegeneration, we assessed association of SNVs with neurocognitive performance people HIV (PWH) using a candidate gene approach. This retrospective study included CHARTER cohort participants, excluding those severe neuropsychiatric comorbidities. Genome-wide data previously obtained 1047 participants and targeted sequencing 992 available genomic...