A5041518902- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- HIV/AIDS drug development and treatment
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Cancer-related Molecular Pathways
- Influenza Virus Research Studies
- Cell death mechanisms and regulation
- Animal Virus Infections Studies
- RNA regulation and disease
- Plant Virus Research Studies
- Bacteriophages and microbial interactions
University of Pennsylvania
2022-2024
National Institute on Aging
2018-2023
Penn Center for AIDS Research
2022
Villanova University
2021
Johns Hopkins University
2014
Abstract Understanding the complexity of long-lived HIV reservoir during antiretroviral therapy (ART) remains a considerable impediment in research towards cure for HIV. To address this, we developed single-cell strategy to precisely define unperturbed peripheral blood HIV-infected memory CD4 + T cell from ART-treated people living with (ART-PLWH) via presence integrated accessible proviral DNA concert epigenetic and surface protein profiling. We identified profound heterogeneity within...
Abstract The nuclear factor kappa B (NF-κB) family of transcription factors orchestrates signal-induced gene expression in diverse cell types. Cellular responses to NF-κB activation are regulated at the level and signal specificity, as well differential use members (subunit specificity). Here we used time-dependent multi-omics investigate selective functions Rel RelA, two closely related proteins, primary lymphocytes activated via receptor. Despite large numbers shared binding sites genome...
Transcription factor nuclear kappa B (NF-κB) regulates cellular responses to environmental cues. Many stimuli induce NF-κB transiently, making time-dependent transcriptional outputs a fundamental feature of activation. Here we show that target genes have distinct kinetic patterns in activated lymphoma cells. By combining RELA binding, RNA polymerase II (Pol II) recruitment, and perturbation activation, demonstrate differences amongst early- late-activated can be understood based on chromatin...
BACKGROUNDEarly antiretroviral therapy initiation (ARTi) in HIV-1 restricts reservoir size and diversity while preserving immune function, potentially improving opportunities for immunotherapeutic cure strategies. For antibody-based approaches, the development of autologous neutralizing antibodies (anAbs) after acute/early ARTi is relevant but poorly understood.METHODSWe characterized antibody responses a cohort 23 participants following acute HIV (<60 days acquisition) early (60-128...
Significance The prevailing dogma is that renewed mitogenic signaling essential to traverse G1 phase of the cell cycle after each division. B lymphocytes undergo multiple mitotic divisions, termed clonal expansion, expand antigen-specific cells mediate effective immunity. Here we demonstrate have undergone one division continue proliferate even in absence further signals. This mitogen-independent proliferation accompanied by an altered marked transcriptomic and proteomic features G2/M....
Transmitted/founder (TF) simian-human immunodeficiency viruses (SHIVs) express HIV-1 envelopes modified at position 375 to efficiently infect rhesus macaques while preserving authentic Env biology. SHIV.C.CH505 is an extensively characterized virus encoding the TF CH505 mutated shown recapitulate key features of immunobiology, including CCR5-tropism, a tier 2 neutralization profile, reproducible early viral kinetics, and immune responses. used frequently in nonhuman primate studies HIV, but...
Abstract The canonical view of the cell cycle posits that G1 progression signals are essential after each mitosis to enter S phase. A subset tumor cells bypass this requirement and progress next division in absence continued signaling. B T lymphocytes adaptive immune system undergo a proliferative burst, termed clonal expansion, generate pools antigen specific for effective immunity. There is evidence rules lymphocyte digress from model. Here we show sustain several rounds...
Abstract Polyfunctionality is a hallmark of protective immunity against pathogens and cancer. However, the molecular mechanisms governing induction polyfunctional T cells are not completely understood. We found that during antigen-driven expansion human virus-specific cells, Wnt pathway activation enhances CD62L+, CD28+, KLRG1- central memory cell phenotype promoted generation highly cells. Such effects only seen in influenza-specific responses but also terminally differentiated CMV-...
Abstract Understanding the complexity of long-lived HIV reservoir during antiretroviral therapy (ART) remains a major impediment for cure research. To address this, we developed single-cell viral ASAPseq to precisely define unperturbed peripheral blood HIV-infected memory CD4+ T cell from treated people living with (ART-PLWH) via presence integrated accessible proviral DNA in concert epigenetic and surface protein profiling. We identified profound heterogeneity within between ART-PLWH,...
Abstract Transmitted/founder (TF) simian-human immunodeficiency viruses (SHIVs) express HIV-1 envelopes modified at position 375 to efficiently infect rhesus macaques while preserving authentic Env biology. TF SHIV.C.CH505 is an extensively characterized virus shown recapitulate key features of immunobiology, including CCR5-tropism, a tier 2 neutralization profile, reproducible early viral kinetics, and immune responses. used frequently in nonhuman primate studies HIV, but loads after months...
The goal of this lesson is to introduce students the lytic and lysogenic cycles T4 lambda bacteriophages, respectively, using student-centered pedagogies. Bacteriophages are viruses that infect bacteria either virulent or temperate; phages can only undergo cycle, which results in death host cell, while temperate latter long-term association between virus. significantly affect bacterial population nature even attractive therapeutic interventions for some infections humans. Therefore, was...