A5025657472- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Neuroinflammation and Neurodegeneration Mechanisms
- Platelet Disorders and Treatments
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Blood groups and transfusion
- Primate Behavior and Ecology
- COVID-19 Clinical Research Studies
- Insect and Pesticide Research
- MicroRNA in disease regulation
- Blood properties and coagulation
- HIV-related health complications and treatments
- Bone and Dental Protein Studies
- Reproductive System and Pregnancy
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Animal testing and alternatives
- Animal Behavior and Welfare Studies
- Advanced Drug Delivery Systems
- Animal Ecology and Behavior Studies
- Ocular Surface and Contact Lens
- Virology and Viral Diseases
Johns Hopkins University
2015-2025
Johns Hopkins Medicine
2015-2025
Massachusetts Institute of Technology
2019-2024
St Clements University Higher Education School
2022
Creative Commons
2022
Johns Hopkins University Center for AIDS Research
2017
University of Rochester
2013
Background It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 B; 31-year-old after infection with peak plasma RNA 220 copies/mL 3,343 copies/mL, respectively. Extensive testing blood tissue for persistence was performed, PrEP...
Abstract Extracellular vesicles (EVs) have potential in disease treatment since they can be loaded with therapeutic molecules and engineered for retention by specific tissues. However, questions remain on optimal dosing, administration pharmacokinetics. Previous studies addressed biodistribution pharmacokinetics rodents, but little evidence is available larger animals. Here, we investigated the of Expi293F‐derived EVs labelled a highly sensitive nanoluciferase reporter (palmGRET) non‐human...
Objective: Resting CD4+ T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed contribution brain to viral latency reactivation. Design: Pigtailed macaques were dual inoculated with SIVDeltaB670 SIV17E-Fr treated efficacious central nervous system-penetrant ART. After 500 days suppression animals two cycles reversing...
Although platelets are the cellular mediators of thrombosis, they also immune cells. Platelets interact both directly and indirectly with cells, impacting their activation differentiation, as well all phases response. Megakaryocytes (Mks) cell source circulating platelets, until recently Mks were typically only considered bone marrow-resident (BM-resident) However, platelet-producing reside in lung, lung express greater levels molecules compared BM Mks. We therefore sought to define...
The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 1) has shown robust anticancer efficacy in preclinical and clinical studies, but its development was halted due to marked systemic toxicities. Herein we demonstrate that DON inhibits metabolism provides antitumor a murine model of glioblastoma, although toxicity observed. To enhance DON's therapeutic index, utilized prodrug strategy increase brain delivery limit exposure. Unexpectedly, simple alkyl ester-based prodrugs were...
Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human clinical isolate acute respiratory syndrome 2 (SARS-CoV-2).
Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding all viral reservoirs that could contribute to rebound after ART interruption. CD4 T cells (CD4s) are recognized as predominant reservoir HIV type 1 (HIV-1)-infected individuals. However, macrophages also infected by HIV-1 and simian (SIV) during acute infection may persist throughout ART, contributing size latent reservoir. We sought determine...
Understanding the cellular and anatomical sites of latent virus that contribute to human immunodeficiency (HIV) rebound is essential for eradication. In HIV-positive patients, CD4+ T lymphocytes comprise a well-defined functional reservoir, defined as cells containing transcriptionally silent genomes able produce infectious once reactivated. However, persistence in compartments other than blood lymph nodes unclear. Macrophages (Mϕ) are infected by HIV/simian (SIV) likely carry viral during...
Background. Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies effective. The gold standard quantitative outgrowth assay (QVOA) underestimates the magnitude reservoir. We sought xenograft leukocytes from HIV type 1 (HIV)–infected into immunocompromised mice would result amplification.
Platelets are key participants in innate immune responses to pathogens. As a decrease circulating platelet count is one of the initial hematologic indicators human immunodeficiency virus (HIV) infection, we sought determine whether decline number during acute infection results from decreased production, increased antibody-mediated destruction, or activation simian (SIV)/macaque model. During SIV platelets were activated with surface expression P-selectin, CD40L and major histocompatibility...
The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone and gastrointestinal are two major causes morbidity mortality captive marmosets, but currently no effective antemortem tests available identify affected animals prior terminal stage disease. In this study we propose bone associated entities marmosets aim establish efficacy several economical identifying predicting Tissues...
Diastolic dysfunction is a highly prevalent cardiac abnormality in asymptomatic as well ART-treated human immunodeficiency virus (HIV) patients. Although the mechanisms underlying depressed function remain obscure, diastolic SIV-infected rhesus macaques correlated with myocardial viral load. As cardiomyocytes are not productively infected, damage may be an indirect process attributable to combination of pro-inflammatory mediators and proteins.Given diverse roles CCR5 mediating recruitment...
HIV-associated neurocognitive deficits remain a challenge despite suppressive combined antiretroviral therapy. Given the association between HIV-induced central nervous system (CNS) disease and replication of HIV in immune-activated macrophages, CCR5 antagonists may attenuate CNS by modulating inflammatory signaling limiting viral replication.To establish whether initiating inhibition during early infection altered progression, outcomes were compared simian immunodeficiency virus...
Measles remains one of the most important causes worldwide morbidity and mortality in children. virus (MeV) replicates extensively lymphoid tissue deaths are due to other infectious diseases associated with MeV-induced loss circulating antibodies pathogens. To determine whether remdesivir, a broad-spectrum direct-acting antiviral, affects antibody pathogens, we expanded VirScan technology detect both human macaque We measured reactivity MeV non-MeV viral peptides using plasma from...
The common marmoset ( Callithrix jacchus) is a New World primate that used in biomedical research due to its small size and relative ease of handling compared with larger primates. Although bone disease marmosets well recognized, there are very few detailed descriptions the literature cover range lesions seen these animals. For all animals model human disease, it important be aware background may affect interpretation study findings. This retrospective details diseases encountered breeding...
Abstract Background Osteopontin (OPN) as a secreted signaling protein is dramatically induced in response to cellular injury and neurodegeneration. Microglial inflammatory responses the brain are tightly associated with neuropathologic hallmarks of neurodegenerative disease, but understanding molecular mechanisms remains several contexts poorly understood. Methods Micro-positron emission tomography (PET) neuroimaging using radioligands detect increased expression translocator (TSPO) receptor...
Peripheral neuropathy is the most frequent neurological complication of HIV infection, affecting more than one-third infected patients, including patients treated with antiretroviral therapy. Although emerging noninvasive techniques for corneal nerve assessments are increasingly being used to diagnose and monitor peripheral neuropathies, alterations have not been characterized in HIV. Here, determine whether SIV infection leads fiber loss, we immunostained corneas marker βIII tubulin. We...
Abstract Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there dearth information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans characterized by any intentional self-directed that leads to wounds, whereas macaques it not always accompanied wounds. We describe cohort rhesus displaying as adults, which changes within central nervous system were associated with SIB. In these macaques, increases striatal...
Abstract Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy available. We evaluated both post-exposure prophylaxis and treatment remdesivir, broad-spectrum antiviral, using well-characterized rhesus macaque model measles. Animals were treated intravenous remdesivir for 12 days beginning either 3 after intratracheal (post-exposure prophylaxis, PEP) or...