A5025099062- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Blood Coagulation and Thrombosis Mechanisms
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Hemophilia Treatment and Research
- Peptidase Inhibition and Analysis
- Mosquito-borne diseases and control
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Single-cell and spatial transcriptomics
- Cellular Mechanics and Interactions
- Radiation Effects and Dosimetry
- Radiation Therapy and Dosimetry
- Toxin Mechanisms and Immunotoxins
- Hematopoietic Stem Cell Transplantation
- Cell death mechanisms and regulation
- Hepatitis C virus research
- Heat shock proteins research
- Platelet Disorders and Treatments
- Plant Genetic and Mutation Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune responses and vaccinations
University of Michigan
1997-2024
Michigan United
2017-2024
VA San Diego Healthcare System
2009-2022
University of California, San Diego
2013
Cincinnati Children's Hospital Medical Center
1999
Howard Hughes Medical Institute
1997-1998
Harvard University
1986
Deoxyribonucleic acid (DNA) of the human immunodeficiency virus (HIV) provides most sensitive measurement residual infection in patients on effective combination antiretroviral therapy (cART). Droplet digital PCR (ddPCR) has recently been shown to provide highly accurate quantification DNA copy number, but its application HIV DNA, or other equally rare targets, not reported. This paper demonstrates and analyzes ddPCR measure frequency total (pol copies per million cells), episomal 2-LTR...
Detection of occult carcinoma in patients with breast cancer may aid the establishment prognosis and development new therapeutic approaches. To improve on existing methods detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for keratin 19 (K19) transcripts to identify mammary cells peripheral blood bone marrow cancer.Peripheral-blood or samples obtained from 34 stages I IV 39 control subjects without were screened K19 mRNA by nested primer PCR.In...
The possibility of HIV-1 eradication has been limited by the existence latently infected cellular reservoirs. Studies to examine control HIV latency and potential reactivation have hindered small numbers cells found in vivo. Major conceptual leaps facilitated use T cell lines primary cells. However, notable differences exist among model systems. Furthermore, screening efforts specific models identified drug candidates for “anti-latency” therapy, which often fail reactivate uniformly across...
Abstract In human neutrophils, IL-8 induces chemotaxis, the respiratory burst, and granule release, enhances cellular adhesion, a β2 integrin-dependent event. stimulates neutrophil adhesion to purified fibrinogen in Mac-1-dependent manner. Mitogen-activated protein kinase (MAPK) activation was detected lysates after treatment with PMA, but not activating mAb CBR LFA 1/2. IL-8-stimulated blocked 50% by MAPK/extracellular signal-related kinase-activating enzyme inhibitor PD098059. Adhesion...
Combinations of drugs that affect distinct mechanisms HIV latency aim to induce robust reversal leading cytopathicity and elimination the persistent reservoir. Thus far, attempts have focused on combinations protein kinase C (PKC) agonists pan-histone deacetylase inhibitors (HDIs) despite knowledge gene expression is regulated by class 1 histone deacetylases. We hypothesized 1-selective HDIs would promote more in combination with a PKC agonist than pan-HDIs because they preserve activity...
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor are heterogeneous population cells, some which long-lived. CXCR4-tropic HIVs infect broad range HSPC subtypes, including hematopoietic multi-potent However, CCR5-tropic limited more differentiated with life spans that less well understood. Consistent emerging data restricted can be long-lived, we detected persistent in populations from optimally treated people. Further, genotypic...
Combined Factors V and VIII deficiency is an autosomal recessive bleeding disorder identified in at least 58 families comprising a number of different ethnic groups. Affected patients present with moderate tendency have Factor levels the range 5-30% normal. The highest frequency mutant gene found Jews Sephardic Middle Eastern origin living Israel estimated disease 1:100,000. We sought to identify responsible for combined using positional cloning approach. Of 14 affected individuals from 8...
Long-lived reservoirs of persistent HIV are a major barrier to cure. CD4+ hematopoietic stem and progenitor cells (HSPCs) have the capacity for lifelong survival, self-renewal, generation daughter cells. Recent evidence shows that they also susceptible infection in vitro vivo. Whether HSPCs harbor infectious virus or contribute plasma (PV) is unknown. Here, we provide strong clusters identical proviruses from their likely progeny often match residual PV. A higher proportion these sequences...
HIV-1 Vpr is necessary for maximal HIV infection and spread in macrophages. Evolutionary conservation of suggests an important yet poorly understood role macrophages pathogenesis. counteracts a previously unknown macrophage-specific restriction factor that targets reduces the expression Env. Here, we report macrophage mannose receptor (MR), targeting Env primary human monocyte-derived acts synergistically with Nef to target distinct stages MR biosynthetic pathway dramatically reduce...
To assess the off-target effects of histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) in human primary CD4 T cells.A pharmacologically relevant concentration (340 nmol/l) SAHA was shown to significantly increase hyperacetylation by 24 h and this length treatment selected determine its impact on gene expression cells.Illumina Beadchips for microarray analysis were used analyze differential between cells treated or not with a paired using multivariate permutation...
Nef is an HIV-encoded accessory protein that enhances pathogenicity by down-regulating major histocompatibility class I (MHC-I) expression to evade killing cytotoxic T lymphocytes (CTLs). A potent inhibitor restores MHC-I needed promote immune-mediated clearance of HIV-infected cells. We discovered the plecomacrolide family natural products restored surface Nef-expressing primary cells with variable potency. Concanamycin (CMA) counteracted at subnanomolar concentrations did not interfere...
Latently infected CD4 T cells form a stable reservoir of HIV that leads to life-long viral persistence; the mechanisms involved in establishment this latency are not well understood. Three scenarios have been proposed: 1) an activated, proliferating cell becomes and reverts back resting state; 2) activated during its return resting; or 3) infection is established directly cell. The aim study was, therefore, investigate relationship between activation proliferation latency. Isolated primary...
The human immunodeficiency virus (HIV)-encoded accessory protein Nef enhances pathogenicity by reducing major histocompatibility complex I (MHC-I) cell surface expression, protecting HIV-infected cells from immune recognition. Nef-dependent downmodulation of MHC-I can be reversed subnanomolar concentrations concanamycin A (1), a well-known inhibitor vacuolar ATPase, at below those that interfere with lysosomal acidification or degradation. We conducted structure–activity relationship study...
Despite effective treatment, Human immunodeficiency virus (HIV) persists in optimally treated people as a transcriptionally silent provirus. Latently infected cells evade the immune system and harmful effects of virus, thereby creating long-lasting reservoir HIV. To gain deeper insight into molecular mechanisms HIV latency establishment, we constructed series HIV-1 fluorescent reporter viruses that distinguish active versus latent infection. We unexpectedly observed proportion...
A major obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1) is a sub-population latently infected CD4(+) T lymphocytes. The cellular and viral mechanisms regulating HIV-1 latency are not completely understood, promising technique for probing regulation single-cell time-lapse microscopy. Unfortunately, lymphocytes rapidly migrate on substrates spontaneously detach, making them exceedingly difficult to track, hampering level studies. To overcome these problems, we built...
We have previously identified Id- tumor vaiants that emerge after anti-Id mAb therapy of the murine B cell lymphoma 38C13. This report characterizes molecular basis for these variants. By using a modification polymerase chain reaction (PCR), mu and kappa Ig loci were sequenced from nine variants derived directly by immunoselection in vivo. sequence analysis was also performed 10 additional amplified cells vitro without immunoselection. demonstrate mechanism underlying escape this model is...