A5053861341- HIV Research and Treatment
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Vagus Nerve Stimulation Research
- Gut microbiota and health
- Gastrointestinal motility and disorders
- Ion Channels and Receptors
- Asthma and respiratory diseases
- Neuropeptides and Animal Physiology
- Regulation of Appetite and Obesity
- HIV-related health complications and treatments
- Hearing, Cochlea, Tinnitus, Genetics
- Infant Health and Development
- Neuroendocrine regulation and behavior
- Diet and metabolism studies
- Exercise and Physiological Responses
- Biochemical effects in animals
- Calcium signaling and nucleotide metabolism
- Peptidase Inhibition and Analysis
- Neuroscience of respiration and sleep
- IL-33, ST2, and ILC Pathways
- Cytomegalovirus and herpesvirus research
- Vestibular and auditory disorders
- Cellular transport and secretion
- vaccines and immunoinformatics approaches
Harvard University
2011-2021
Wesleyan University
2021
Marine Biological Laboratory
2021
Boston Children's Hospital
2015-2021
Ragon Institute of MGH, MIT and Harvard
2011-2015
A distinct population of Foxp3 + CD4 regulatory T (Treg) cells promotes repair acutely or chronically injured skeletal muscle. The accumulation these depends critically on interleukin (IL)-33 produced by local mesenchymal stromal (mSCs). An intriguing physical association among muscle nerves, IL-33 mSCs, and Tregs has been reported, invites a deeper exploration this cell triumvirate. Here we evidence striking proximity between mSCs both large-fiber nerve bundles small-fiber sensory neurons;...
Induction of virus-specific CD8+ T cell responses is critical for the success vaccines against chronic viral infections. Despite large number potential MHC-I–restricted epitopes located in proteins, epitope generation inefficient, and factors defining production presentation are poorly understood. Here, we have demonstrated that half-lives HIV-derived peptides cytosol from primary human cells were highly variable sequence dependent, significantly affected efficiency recognition by cells....
Dendritic cells (DCs) and macrophages (Møs) internalize process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8+ T (CTL). However, how degradation patterns of HIV in the pathways affect immunodominance immune escape is poorly defined. Here, we studied processing dominant subdominant HIV-1 Gag-derived epitopes HLA-restricted mutants monocyte-derived DCs Møs. The proteins both Møs led higher CTL responses specific immunodominant epitopes. low were increased...
Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact most on epitope production and presentation remains unclear. The multistep breakdown proteins into epitopes includes trimming N-extended peptides by aminopeptidases before loading onto MHC class I molecules. Definition sequence signatures...
Abstract Dendritic cells (DCs), macrophages (MPs), and monocytes are permissive to HIV. Whether they similarly process present HIV epitopes HIV-specific CD8 T is unknown despite the critical role of peptide processing presentation for recognition clearance infected cells. Cytosolic peptidases degrade endogenous proteins originating from self or pathogens, exogenous Ags preprocessed in endolysosomes, thus shaping peptidome available endoplasmic reticulum translocation, trimming, MHC-I...
Abstract Background Endolysosomes play a key role in maintaining the homeostasis of cell. They are made complex set proteins that degrade lipids, and sugars. Studies involving endolysosome contribution to cellular functions such as MHC class I II epitope production have used recombinant endolysosomal proteins, knockout mice lack one enzymes or purified organelles from human tissue. Each these approaches has some caveats analyzing enzyme functions. Results In this study, we developed simple...
SUMMARY Gut-innervating nociceptor sensory neurons respond to noxious/tissue-damaging stimuli by initiating protective responses and releasing mediators that regulate tissue inflammation, gastrointestinal secretion, motility. The role of nociceptors in host defense against enteric pathogens is unclear. Here, we found gut-extrinsic are critical protecting the Salmonella typhimurium (STm) infection. Nociceptors responded STm neuropeptide calcitonin gene-related peptide (CGRP). Targeted...
Abstract HIV-specific CD8 T cells (CTL) play a major role in reducing viral load acute HIV infection and the spontaneous control of viremia. infects CD4 cells, monocytes, macrophages dendritic cells. Whether these subsets have equivalent capacity to produce present MHC-I restricted epitopes is unknown. We analyzed effect TLR agonist-mediated maturation on processing presentation antigens monocyte-derived (DC) (MP). LPS-induced decreased significantly proteasomal tryptic activity lysosomal...
Background Whether HIV-infectable subsets, such as CD4 T cells, monocytes, macrophages and dendritic cells (DCs), have equivalent capacity to produce present MHC-I restricted epitopes HIV-specific CD8 is unknown. are processed by an intracellular degradation pathway involving multiple proteases. In this study we analyzed the effect of toll-like receptor (TLR) agonist-mediated maturation on processing presentation HIV antigens in monocyte-derived DCs macrophages.
Movement induces sensory stimulation of an animal's own receptors, termed reafference. With a few exceptions, notably vestibular and proprioception, this reafference is unwanted noise must be selectively filtered in order to detect relevant external signals. In the cerebellum-like electrosensory nucleus elasmobranch fish, adaptive filter preserves novel signals by generating cancellation that suppress predictable A parallel fiber network supplies principal Purkinje-like neurons (called...