Sanjay Menghani | University of Pennsylvania (original) (raw)

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Papers by Sanjay Menghani

Research paper thumbnail of Demonstration of N , N -Dimethyldithiocarbamate as a Copper-Dependent Antibiotic against Multiple Upper Respiratory Tract Pathogens

Microbiology Spectrum

With the rise of antibiotic resistance, approaches that add new antimicrobials to the current rep... more With the rise of antibiotic resistance, approaches that add new antimicrobials to the current repertoire are vital. Here, we investigate putative and known copper ionophores in an attempt to intoxicate bacteria and use ionophore/copper synergy, and we ultimately find success with N , N -dimethyldithiocarbamate (DMDC). We show that DMDC has in vitro efficacy in a copper-dependent manner and kills pathogens across three different kingdoms, Streptococcus pneumoniae ( Sr. pneumoniae ), Coccidioides posadasii , and Schistosoma mansoni , and in vivo efficacy against Sr . pneumoniae .

Research paper thumbnail of CC16 Binding to α4β1 Integrin Protects against Mycoplasma pneumoniae Infection

American Journal of Respiratory and Critical Care Medicine

Research paper thumbnail of Comparison of Clinical Outcomes Between Short, Intermediate, and Long Cephalomedullary Nails: A Retrospective Review

Journal of the American College of Surgeons

Research paper thumbnail of A quantitative enzyme-linked immunoassay (ELISA) to approximate complement-fixing antibody titers in serum from patients with coccidioidomycosis

Diagnostic Microbiology and Infectious Disease

Research paper thumbnail of Rules of Expansion: an Updated Consensus Operator Site for the CopR-CopY Family of Bacterial Copper Exporter System Repressors

mSphere

Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export sys... more Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repressor binding. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, homologs of pneumococcal CopY have been characterized to bind a 10-base consensus sequence T/GACANNTGTA known as the cop box. Using this motif, we sought to determine whether genes outside the cop operon are also regulated by the CopY repressor, which was previously shown in Lactococcus lactis. We found that S. pneumoniae CopY did not bind to cop operators upstream of these candidate genes in vitro. During this process, we found that the cop bo...

Research paper thumbnail of Gastric Cardia Adenocarcinoma with Metastasis to the Scalp: A Case Report

Cureus, Jan 27, 2020

Cutaneous metastasis is a rare manifestation of advanced gastrointestinal (GI) cancers. Gastric a... more Cutaneous metastasis is a rare manifestation of advanced gastrointestinal (GI) cancers. Gastric adenocarcinoma rarely presents with cutaneous metastasis, as cutaneous manifestations occur in less than 1% of upper GI tract malignancies. Here, we present the case of a patient with advanced gastric cardia adenocarcinoma with metastasis to the right occipital region of the scalp. Following shave biopsy, the immunohistochemistry (IHC) and molecular profile of the scalp lesion were analyzed, both of which confirmed metastasis and guided the treatment approach. The lesion demonstrated programmed death ligand-1 (PD-L1), an immune checkpoint protein, positivity by IHC, which led to the recommendation for treatment with immunotherapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Clinicians should conduct dermatologic examinations in patients with a history of gastric cancer or who are currently undergoing chemotherapy for gastric cancer in order to monitor for disease progression or metastatic lesions. The aim of this report is to increase awareness of scalp metastasis as an indicator of advanced internal visceral carcinoma for earlier diagnosis and improved management of the condition.

Research paper thumbnail of Characterization of consensus operator site for Streptococcus pneumoniae copper repressor, CopY

Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export sys... more Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repression. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, these homologs have been characterized to bind a 10-base consensus sequence T/GACAnnTGTA. Here, we bioinformatically and empirically characterize these operator sites across species using S. pneumoniae CopY as a guide for binding. By examining the 21-base repeat operators for the pneumococcal cop operon and comparing binding of recombinant CopY to this, and the operator sites found in Enterococcus hirae, we show using biolayer interferometry that the ...

Research paper thumbnail of A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

Genes & Development, 2016

RNA degradation is tightly regulated to selectively target aberrant RNAs, including viral RNA, bu... more RNA degradation is tightly regulated to selectively target aberrant RNAs, including viral RNA, but this regulation is incompletely understood. Through RNAi screening in Drosophila cells, we identified the 3 ′-to-5 ′ RNA exosome and two components of the exosome cofactor TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) complex, dMtr4 and dZcchc7, as antiviral against a panel of RNA viruses. We extended our studies to human orthologs and found that the exosome as well as TRAMP components hMTR4 and hZCCHC7 are antiviral. While hMTR4 and hZCCHC7 are normally nuclear, infection by cytoplasmic RNA viruses induces their export, forming a cytoplasmic complex that specifically recognizes and induces degradation of viral mRNAs. Furthermore, the 3 ′ untranslated region (UTR) of bunyaviral mRNA is sufficient to confer virus-induced exosomal degradation. Altogether, our results reveal that signals from viral infection repurpose TRAMP components to a cytoplasmic surveillance role where they selectively engage viral RNAs for degradation to restrict a broad range of viruses.

Research paper thumbnail of Demonstration of N , N -Dimethyldithiocarbamate as a Copper-Dependent Antibiotic against Multiple Upper Respiratory Tract Pathogens

Microbiology Spectrum

With the rise of antibiotic resistance, approaches that add new antimicrobials to the current rep... more With the rise of antibiotic resistance, approaches that add new antimicrobials to the current repertoire are vital. Here, we investigate putative and known copper ionophores in an attempt to intoxicate bacteria and use ionophore/copper synergy, and we ultimately find success with N , N -dimethyldithiocarbamate (DMDC). We show that DMDC has in vitro efficacy in a copper-dependent manner and kills pathogens across three different kingdoms, Streptococcus pneumoniae ( Sr. pneumoniae ), Coccidioides posadasii , and Schistosoma mansoni , and in vivo efficacy against Sr . pneumoniae .

Research paper thumbnail of CC16 Binding to α4β1 Integrin Protects against Mycoplasma pneumoniae Infection

American Journal of Respiratory and Critical Care Medicine

Research paper thumbnail of Comparison of Clinical Outcomes Between Short, Intermediate, and Long Cephalomedullary Nails: A Retrospective Review

Journal of the American College of Surgeons

Research paper thumbnail of A quantitative enzyme-linked immunoassay (ELISA) to approximate complement-fixing antibody titers in serum from patients with coccidioidomycosis

Diagnostic Microbiology and Infectious Disease

Research paper thumbnail of Rules of Expansion: an Updated Consensus Operator Site for the CopR-CopY Family of Bacterial Copper Exporter System Repressors

mSphere

Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export sys... more Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repressor binding. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, homologs of pneumococcal CopY have been characterized to bind a 10-base consensus sequence T/GACANNTGTA known as the cop box. Using this motif, we sought to determine whether genes outside the cop operon are also regulated by the CopY repressor, which was previously shown in Lactococcus lactis. We found that S. pneumoniae CopY did not bind to cop operators upstream of these candidate genes in vitro. During this process, we found that the cop bo...

Research paper thumbnail of Gastric Cardia Adenocarcinoma with Metastasis to the Scalp: A Case Report

Cureus, Jan 27, 2020

Cutaneous metastasis is a rare manifestation of advanced gastrointestinal (GI) cancers. Gastric a... more Cutaneous metastasis is a rare manifestation of advanced gastrointestinal (GI) cancers. Gastric adenocarcinoma rarely presents with cutaneous metastasis, as cutaneous manifestations occur in less than 1% of upper GI tract malignancies. Here, we present the case of a patient with advanced gastric cardia adenocarcinoma with metastasis to the right occipital region of the scalp. Following shave biopsy, the immunohistochemistry (IHC) and molecular profile of the scalp lesion were analyzed, both of which confirmed metastasis and guided the treatment approach. The lesion demonstrated programmed death ligand-1 (PD-L1), an immune checkpoint protein, positivity by IHC, which led to the recommendation for treatment with immunotherapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Clinicians should conduct dermatologic examinations in patients with a history of gastric cancer or who are currently undergoing chemotherapy for gastric cancer in order to monitor for disease progression or metastatic lesions. The aim of this report is to increase awareness of scalp metastasis as an indicator of advanced internal visceral carcinoma for earlier diagnosis and improved management of the condition.

Research paper thumbnail of Characterization of consensus operator site for Streptococcus pneumoniae copper repressor, CopY

Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export sys... more Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repression. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, these homologs have been characterized to bind a 10-base consensus sequence T/GACAnnTGTA. Here, we bioinformatically and empirically characterize these operator sites across species using S. pneumoniae CopY as a guide for binding. By examining the 21-base repeat operators for the pneumococcal cop operon and comparing binding of recombinant CopY to this, and the operator sites found in Enterococcus hirae, we show using biolayer interferometry that the ...

Research paper thumbnail of A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

Genes & Development, 2016

RNA degradation is tightly regulated to selectively target aberrant RNAs, including viral RNA, bu... more RNA degradation is tightly regulated to selectively target aberrant RNAs, including viral RNA, but this regulation is incompletely understood. Through RNAi screening in Drosophila cells, we identified the 3 ′-to-5 ′ RNA exosome and two components of the exosome cofactor TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) complex, dMtr4 and dZcchc7, as antiviral against a panel of RNA viruses. We extended our studies to human orthologs and found that the exosome as well as TRAMP components hMTR4 and hZCCHC7 are antiviral. While hMTR4 and hZCCHC7 are normally nuclear, infection by cytoplasmic RNA viruses induces their export, forming a cytoplasmic complex that specifically recognizes and induces degradation of viral mRNAs. Furthermore, the 3 ′ untranslated region (UTR) of bunyaviral mRNA is sufficient to confer virus-induced exosomal degradation. Altogether, our results reveal that signals from viral infection repurpose TRAMP components to a cytoplasmic surveillance role where they selectively engage viral RNAs for degradation to restrict a broad range of viruses.