A5078241841- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Phagocytosis and Immune Regulation
- Immune responses and vaccinations
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Pneumocystis jirovecii pneumonia detection and treatment
- TGF-β signaling in diseases
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 diagnosis using AI
- Cytomegalovirus and herpesvirus research
- Calcium signaling and nucleotide metabolism
- Pancreatic and Hepatic Oncology Research
- Radiomics and Machine Learning in Medical Imaging
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Escherichia coli research studies
- Infectious Diseases and Tuberculosis
- Colorectal Cancer Treatments and Studies
Scholar Rock (United States)
2019-2024
Ragon Institute of MGH, MIT and Harvard
2017-2019
Harvard University
2011-2018
Brigham and Women's Hospital
2011-2012
Inhibiting a specific isoform of TGFβ augments the effectiveness checkpoint blockade therapy in cancer treatment.
ABSTRACT Infection with Mycobacterium tuberculosis causes a spectrum of outcomes; the majority individuals contain but do not eliminate infection, while small subset present primary active (TB) disease. This variability in infection outcomes is recapitulated at granuloma level within each host, such that some sites can be fully cleared others progress. Understanding TB requires new tools to deconstruct mechanisms underlying differences fate. Here, we use novel genome-encoded barcodes...
For many pathogens, including most targets of effective vaccines, infection elicits an immune response that confers significant protection against reinfection. There has been debate as to whether natural Mycobacterium tuberculosis (Mtb) Here we experimentally assessed the conferred by concurrent Mtb in macaques, a robust experimental model human (TB), using combination serial imaging and challenge strains differentiated DNA identifiers. Strikingly, ongoing provided complete establishment...
Abstract Variability in bacterial sterilization is a key feature of Mycobacterium tuberculosis (Mtb) disease. In population human macrophages, there are macrophages that restrict Mtb growth and those do not. However, the sources heterogeneity macrophage state during infection poorly understood. Here, we perform RNAseq on restrictive permissive reveal expression genes involved GM-CSF signaling discriminates between two subpopulations. We demonstrate blocking makes more while addition...
Inhibitors of the transforming growth factor-β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently different presenting molecules within large latent complexes. The TGF-β-binding proteins (LTBPs) present extracellular matrix, and presented on immune cells by two transmembrane proteins, glycoprotein A...
The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. host factors that affect immunodominance incompletely understood. Whether epitopes elicit protective CD8+ or instead act as decoys subvert immunity and allow pathogens establish chronic infection is unknown. Here we show anatomically distinct human granulomas contain clonally expanded cells...
Checkpoint inhibitors offer a promising immunotherapy strategy for cancer treatment; however, due to primary or acquired resistance, many patients do not achieve lasting clinical responses. Recently, the transforming growth factor-β (TGFβ) signaling pathway has been identified as potential target overcome although nonselective inhibition of multiple TGFβ isoforms led dose-limiting cardiotoxicities. SRK-181 is high-affinity, fully human antibody that selectively binds latent TGFβ1 and...
Mycobacterium tuberculosis is an intracellular bacterium that persists in phagosomes of myeloid cells. M. tuberculosis-encoded factors support pathogen survival and reduce fusion with bactericidal lysosomal compartments. It is, however, not entirely understood if host mediate endosomal affect localization survival. Neither it known influences induction immune reactivity by tuberculosis-infected Lysosomal degradation appears to be pivotal for making available lipid substrates assembly into...
Rhode Island Tuberculosis (RI TB) Clinic, The Miriam Hospital, Providence, RI, USA. Human immunodeficiency virus (HIV) status is a critical factor in the management of both patients with latent TB infection (LTBI) and active TB. Since 2006, Centers for Disease Control Prevention has recommended routine, opt-out HIV testing all health care settings, including clinics. However, implementation LTBI been limited. A policy assessment new was instituted at RI Clinic. Patients who reported no...
For many pathogens, including most targets of effective vaccines, infection elicits an immune response that confers significant protection against reinfection. There has been debate as to whether natural M. tuberculosis (Mtb) Here we experimentally assessed the conferred by concurrent Mtb nfection in macaques, a robust experimental model human (TB), using combination serial imaging and challenge strains differentiated DNA identifiers. Strikingly, ongoing provided complete establishment...
Abstract Tuberculosis (TB) continues to pose a significant health risk morbidity and mortality worldwide. The vast majority of individuals infected with M. tuberculosis, the causative agent TB, contain infection as clinically asymptomatic latent TB. A small minority people do not either present primary active disease or reactivate over their lifetime. By examining early events in at local lesion level, we aim uncover some basis for observed spectrum TB host outcome. Using genetically...
Cell death is continual in multicelluar organisms. During development, vestigial organs and structures appear disappear. Webbing between our fingers, which necessary for them to form properly, disappears the 6th 8th weeks of fetal development through programmed cell death. Cells typically have limited life spans. Neutrophils, example, survive only hours days after being released into circulation. Moreover, injury diseases cause cells die.
Abstract Despite the clinical breakthroughs achieved by checkpoint blockade therapy (CBT), a majority of patients treated with PD-(L)1 inhibitors fail to respond due primary or acquired resistance. TGFβ signaling has recently been implicated as mechanism resistance CBT, very likely via mechanisms that include immune exclusion. However, therapeutic targeting pathway hindered dose-limiting cardiotoxicities, most inhibition from multiple isoforms. Upon secretion, growth factor is held dormant...
Despite the clinical breakthroughs achieved by checkpoint blockade therapy (CBT), a majority of patients treated with PD-(L)1 inhibitors fail to respond due primary or acquired resistance. TGFβ signaling has recently been implicated as mechanism resistance CBT, very likely via mechanisms that include immune exclusion. However, therapeutic targeting pathway hindered dose-limiting cardiotoxicities, most inhibition from multiple isoforms. Upon secretion, growth factor is held dormant in latent...