- Macrophage Migration Inhibitory Factor
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Urinary Bladder and Prostate Research
- Urinary Tract Infections Management
- Immune cells in cancer
- Pelvic floor disorders treatments
- Chemokine receptors and signaling
- Pregnancy and preeclampsia studies
- Pneumonia and Respiratory Infections
- Peptidase Inhibition and Analysis
- Intraperitoneal and Appendiceal Malignancies
- Syphilis Diagnosis and Treatment
- Research on Leishmaniasis Studies
- Advanced Breast Cancer Therapies
- COVID-19 Impact on Reproduction
- Bacterial Infections and Vaccines
- Histone Deacetylase Inhibitors Research
- Whipple's Disease and Interleukins
- Diverse Scientific Research Studies
Emory University
2018-2020
University of Pennsylvania
2013-2019
Yale University
2009-2018
North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences
2018
B & B
2018
Baylor College of Medicine
2017
Tripura Medical College & Dr. B.R. Ambedkar Memorial Teaching Hospital
2016
Yale Cancer Center
2014-2015
National Institute of Immunology
2009-2015
Smilow Cancer Hospital
2014
Immune interferon gamma (IFN-γ) is essential for mammalian host defense against intracellular pathogens. IFN-γ induces nearly 2000 genes, yet few have any assigned function. Here, we examined a complete mouse 65-kilodalton (kD) guanylate-binding protein (Gbp) gene family as part of 43-member IFN-γ-inducible guanosine triphosphatase (GTPase) superfamily in and human genomes. Family-wide loss-of-function analysis found that at least four Gbps--Gbp1, Gbp6, Gbp7, Gbp10--conferred cell-autonomous...
Abstract Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both dampen the T cell activation, in vivo effects of these drugs humans remain be clearly defined. To better understand biologic therapy, we analyzed blood/tumor tissue from 45 patients undergoing single or combination checkpoint blockade. We show that blockade CTLA-4, PD-1, two distinct genomic functional signatures purified human cells monocytes....
Combination checkpoint blockade (CCB) targeting inhibitory CTLA4 and PD1 receptors holds promise for cancer therapy. Immune-related adverse events (IRAEs) remain a major obstacle the optimal application of CCB in cancer. Here, we analyzed B cell changes patients with melanoma following treatment either anti-CTLA4 or anti-PD1, combination. therapy led to circulating cells that were detectable after first cycle characterized by decline an increase CD21lo plasmablasts. expression was higher...
BACKGROUND. Multiple myeloma is usually fatal due to serial relapses that become progressively refractory therapy. CD19 typically absent on the dominant multiple cell population but may be present minor subsets with unique myeloma-propagating properties. To target cells, we clinically evaluated autologous T cells transduced a chimeric antigen receptor (CAR) against (CTL019).
Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion MIF does not completely abrogate activation responses, however, and receptor, CD74, produces more pronounced phenotype than deficiency. We hypothesized that these observations may be explained by second MIF-like ligand, we considered probable candidate to protein encoded homologous, D -dopachrome tautomerase (D-DT) gene. show recombinant D-DT binds CD74 with high...
Heterogeneity of tumor cells and their microenvironment can affect outcome in cancer. Blockade immune checkpoints (ICPs) expressed only on a subset leads to durable responses advanced melanoma. Tissue-resident memory T (TRM) have recently emerged as distinct nonlymphoid tissues. Here, we show that functional properties expression ICPs within tumor-infiltrating lymphocytes (TILs) differ from those blood cells. TILs secrete less IL-2, IFN-γ, TNF-α compared with circulating counterparts, VEGF...
Macrophage migration inhibitory factor (MIF), an innate cytokine encoded in a functionally polymorphic genetic locus, contributes to detrimental inflammation but may be crucial for controlling infection. We explored the role of variant MIF alleles tuberculosis. In Ugandan cohort, low expressers were 2.4-times more frequently identified among patients with Mycobacterium tuberculosis (TB) bacteremia than those without. also found mycobacteria-stimulated transcription and serum levels...
BACKGROUNDPD-1 and PD-L1 have been studied interchangeably in the clinic as checkpoints to reinvigorate T cells diverse tumor types. Data for biologic effects of checkpoint blockade human premalignancy are limited.METHODSWe analyzed immunologic a clinical trial atezolizumab patients with asymptomatic multiple myeloma (AMM), precursor malignancy. Genomic signatures purified monocytes vivo were also compared those following PD-1 lung cancer patients. Effects on monocyte-derived DCs better...
Immunotherapeutic strategies including the blockade of programmed death 1 (PD-1) receptors hold promise for treatment various cancers non-small cell lung carcinoma (NSCLC). Preclinical data suggest that pre-existing tumor immunity is important disease regression upon checkpoint blockade-based therapies. However, nature antigen-specific T-cell responses correlate with clinical response to immunotherapy in NSCLC patients not known. The embryonic stem gene SRY (sex determining region Y)-box 2...
In our study of nursing home residents with clinically suspected urinary tract infection who did not require the use an indwelling catheter, we identified bacteria isolated from urine samples, resistance patterns these bacteria, and antibiotic therapy prescribed to residents. Escherichia coli , predominant organism isolated, frequently was resistant commonly oral antibiotics. Trimethoprim-sulfamethoxazole remains best empiric antimicrobial for a infection, but nitrofurantoin should be...
Human genetic polymorphisms associated with decreased expression of macrophage migration inhibitory factor (MIF) have been linked to the risk community-acquired pneumonia. Because Streptococcus pneumoniae is leading cause pneumonia and nasal carriage a precursor invasive disease, we explored role MIF in clearance pneumococcal colonization mouse model. MIF-deficient mice (Mif(-/-)) showed prolonged both avirulent (23F) virulent (6A) serotypes compared wild-type animals. Pneumococcal led local...
We examined the association between an increase in episodes of observed bacteriuria and adverse clinical outcomes among nursing home residents without catheters. Although was not associated with hospitalization for urinary tract infection (UTI) or change mental status, it use antibiotics to treat UTI isolation multidrug-resistant gram-negative rods from urine specimens, which suggested a causal relationship.
Mortality from pneumococcal pneumonia remains high despite antibiotic therapy, highlighting the pathogenic potential for host inflammation. We demonstrate that macrophage migration inhibitory factor (MIF), an innate immune mediator, is detrimental survival and associated with lung pathology, inflammatory cellular infiltration, bacterial replication in a mouse model of pneumonia, being necessary clearance nasopharynx. Treatment animals small-molecule inhibitor MIF improves by reducing...
Macrophage migration inhibitory factor (MIF) is an immune mediator encoded in a functionally polymorphic locus. We found the genotype conferring low expression of MIF to be enriched cohort 180 patients with gram-negative bacteremia, compared 229 healthy controls (odds ratio [OR], 2.4; P = .04), association that was more pronounced older adults (OR, 4.6; .01). Among subjects, those demonstrated 20% reduced production from lipopolysaccharide-stimulated peripheral blood monocytes and 30% lower...
Poor T cell immunity is one of the many defects seen in elderly humans and aged (Ad) mice. We report that naive CD4 cells from mice (ANCD4 cells) showed greater apoptosis upon primary activation than those young (Yg) mice, with loss mitochondrial membrane potential, poor Rel family transcription factors increased DNA damage. Their ability to enhance glycolysis, produce lactate induce autophagy following was also compromised. ANCD4 remained susceptible death beyond first division. Activated...
Introduction: A study was conducted for six randomly selected designated Microscopy Centre areas of West Tripura District India with objectives to assess the knowledge regarding Pulmonary Tuberculosis (PTB) and DOTS among PTB patients identify factors determining knowledge.Methodology: This cross-sectional 220 registered treatment therapy during July 2011 June 2012.Results: The showed that 29.10% had satisfactory disease its treatment. Only 14.10% correct cause 53.60% mode transmission...
Host immunity is crucial for controlling M. tuberculosis infection. Functional polymorphisms in the cytokine macrophage migration inhibitory factor (MIF) show global population stratification, with highest prevalence of low expression MIF alleles found sub-Saharan Africans, which a greatest confluence both TB and HIV infection disease. We investigated association between (TB) South Africa. acquired clinical information determined frequency two promoter variants: functional −794 CATT5-8...