- Mitochondrial Function and Pathology
- Glioma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Cancer Research and Treatments
- Phagocytosis and Immune Regulation
- Platelet Disorders and Treatments
- Research Data Management Practices
- Occupational and environmental lung diseases
- Galectins and Cancer Biology
- Microplastics and Plastic Pollution
- Plant Molecular Biology Research
- Biomarkers in Disease Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Neurofibromatosis and Schwannoma Cases
- Pregnancy and Medication Impact
- Marine Biology and Environmental Chemistry
- RNA and protein synthesis mechanisms
- Autophagy in Disease and Therapy
- Free Radicals and Antioxidants
Cleveland Clinic Lerner College of Medicine
2021-2024
Cleveland Clinic
2020-2023
King Edward Memorial Hospital and Seth G.S. Medical College
2023
All India Institute of Medical Sciences Jodhpur
2023
Indian Institute of Science Bangalore
2015
Maharaja Sayajirao University of Baroda
2008
The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications on tumor biology are poorly understood. Here we show that is a prevalent phenomenon glioblastoma (GBM), most frequent and malignant primary brain tumor. We identified horizontal from astrocytes as mechanism enhances tumorigenesis GBM. This dependent network-forming intercellular connections GBM cells astrocytes, which facilitated...
The activities of the NLRP3 and AIM2 inflammasomes Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard progression. Using a metastatic Lewis carcinoma (LLC) cell model, we show that GsdmD knockout (GsdmD-/-) mice form significantly fewer foci lungs, exhibit markedly decreased metastasis, significant ∼50% increase median survival rate. cleaved forms IL-1β were detected tumor tissue, indicating inflammasome activity...
Abstract Halophilic archaea belonging to three different genera‐ Halobacterium , Haloarcula and Haloferax were isolated from Kandla salt pans. The isolates had an optimum requirement of 25% NaCl for growth. Increase in organic solvent tolerance was observed at higher concentrations. Among the sp. SP1(1) found be more tolerant than SP2(2) SP1(2a). extracellular protease showed compared organism itself. enzyme highly toluene, xylene, n‐decane, n‐dodecane n‐undecane, majority which are...
Axillary meristems (AMs) are secondary shoot whose outgrowth determines plant architecture.In rice, AMs form tillers, and tillering mutants reveal an interplay between transcription factors the phytohormones auxin strigolactone as some that underpin this developmental process.Previous studies showed knockdown of factor gene RFL reduced caused a very large decrease in panicle branching.Here, relationship RFL, AM initiation, was examined.We show promotes specification through its effects on...
Amino acid ligation to cognate transfer RNAs (tRNAs) is catalyzed by aminoacyl-tRNA synthetases (aaRSs)—essential interpreters of the genetic code during translation. Mammalian cells harbor 20 cytoplasmic aaRSs, out which 9 (in 8 proteins), with 3 non-aaRS proteins, AIMPs 1 3, form ∼1.25-MDa multi-tRNA synthetase complex (MSC). The function MSC remains uncertain, as does its mechanism assembly. Constituents multiprotein complexes encounter obstacles assembly, including inappropriate...
Fibroblast to myofibroblast transdifferentiation mediates numerous fibrotic disorders, such as idiopathic pulmonary fibrosis (IPF). We have previously demonstrated that non-muscle myosin II (NMII) is activated in response lung extracellular matrix, thereby mediating transdifferentiation. NMII-A known interact with the calcium-binding protein S100A4, but mechanism by which S100A4 regulates disorders unclear. In this study, we show fibroblast a calcium-dependent, mechanoeffector uniquely...
Glutamyl-prolyl-tRNA synthetase (EPRS1) is a bifunctional aminoacyl-tRNA-synthetase (aaRS) essential for decoding the genetic code. EPRS1 resides, with seven other aaRSs and three noncatalytic proteins, in cytoplasmic multi-tRNA complex (MSC). Multiple MSC-resident aaRSs, including EPRS1, exhibit stimulus-dependent release from MSC to perform noncanonical activities distinct their primary function protein synthesis. Here, we show present both cytoplasm nucleus of breast cancer cells...
The secreted metalloproteases ADAMTS9 and ADAMTS20 are implicated in extracellular matrix proteolysis primary cilium biogenesis. Here, we show that clonal gene-edited RPE-1 cells which was inactivated, constitutively lack expression, have morphologic characteristics distinct from parental cells. To investigate underlying proteolytic mechanisms, a quantitative terminomics method, terminal amine isotopic labeling of substrates used to compare the their medium identify substrates. Among...
Ezrin links the cytoskeleton to cell surface integrins and plasma membrane receptors, contributing proliferative metastatic potential of cancer cells. Elevated ezrin expression in several cancers is associated with poor outcomes. Tumor function have been investigated depth; however, its role macrophages other tumor microenvironment cells remains unexplored. Macrophages profoundly influence tumorigenesis, here we explore ezrin’s on tumor-promoting macrophage functions. knockdown THP-1 reveals...
Multiprotein assemblages are the intracellular workhorses of many physiological processes. Assembly constituents into complexes can be driven by stochastic, domain-dependent, posttranslational events in which mature, folded proteins specifically interact. However, inaccessibility interacting surfaces mature (e.g., due to "buried" domains) obstruct complex formation. Mechanisms multiprotein overcome topological impediments remain enigmatic. For example, heterodimeric formed EBP50 and ezrin...
Abstract Mitochondrial transfer in the central nervous system occurs from astrocytes to neurons stroke. exchange has also been reported among tumor cells glioblastoma (GBM), most common primary brain tumor. However, role of mitochondrial non-neoplastic surrounding microenvironment GBM remains poorly understood. We hypothesized that these supports metabolism and growth. Using transgenic mice expressing fluorophore-tagged mitochondria, we found ~50% orthotopically-implanted mouse acquire host...
Rigor, reproducibility, and transparency (RR&T) are essential components of all scientific pursuits. Shared research resources, also known as core facilities, on the frontlines ensuring robust RR&T practices. The Association Biomolecular Resource Facilities Committee Core Rigor Reproducibility conducted a follow-up survey 4 years after initial 2017 to determine if facilities have seen positive impact new initiatives (including guidance from National Institutes Health, journal requirements...
Abstract Mitochondrial transfer occurs both in stroke (central nervous system) and inflammatory pain (peripheral nerves). However, its role glioblastoma (GBM) remains poorly understood. We hypothesized that mitochondrial from non-malignant to GBM cells supports tumor metabolism growth. Using transgenic mice expressing fluorophore-tagged mitochondria, we found ~50% of orthotopically-implanted mouse acquire mitochondria. Brain-resident cells, especially astrocytes, were the primary donors...
Abstract Glioblastoma (GBM) interaction with neural cells is critical to its pathobiology. Emerging evidence suggests that GBM form an interconnected network astrocytes, facilitating tumor persistence. Given reports of intercellular transfer mitochondria in ischemic stroke and other pathologic disease states outside the CNS, we hypothesized this facilitates from astrocytes protumorigenic sequelae. Employing transgenic mice intracranial viral vector transductions rats, found TME occurs mouse...
Introduction: Ankylosing spondylitis (AS) is an inflammatory spondyloarthropathy that involves the sacroiliac joints and axial skeleton. Sulfasalazine's efficacy in treating symptoms of AS has been a subject controversy. Methods: This prospective observational study recruited patients categorized them into two groups: first group had for less than or equal to four years second more years. Erythrocytic sedimentation rate (ESR) C-reactive protein (CRP) levels were recorded at baseline...
Abstract The activities of the NLRP3 and AIM2 inflammasomes Gasdermin D (GsdmD), final executor inflammasome activity, are implicated in lung cancer pathophysiology but it’s not clear if their contributions promote or retard progression. GsdmD plays a role release interleukin-1beta (IL-1 β), CANTOS trial recent studies have highlighted crucial IL-1β promoting cancer. Expression was shown to be upregulated human non-small cell (NSCLC) tissue, its contribution vivo metastasis is known. Using...
The activities of the NLRP3 and AIM2 inflammasomes Gasdermin D (GsdmD), final executor inflammasome activity, are implicated in lung cancer pathophysiology but it’s not clear if their contributions promote or retard progression. GsdmD plays a role release interleukin-1beta (IL-1β), CANTOS trial recent studies have highlighted crucial IL-1β promoting cancer. Expression was shown to be upregulated human non-small cell (NSCLC) tissue, its contribution vivo metastasis is known. Using metastatic...
Summary The secreted metalloproteases ADAMTS9 and ADAMTS20 are implicated in extracellular matrix (ECM) proteolysis primary cilium biogenesis. Here, we show that clonal gene-edited RPE-1 cells which was inactivated, constitutively lack expression, have morphologic characteristics distinct from parental cells. To investigate underlying proteolytic mechanisms, a quantitative N-terminomics method, terminal amine isotopic labeling of substrates (TAILS) used to compare their medium identify...
Abstract While dynamic microenvironmental interactions drive tumor growth and therapeutic resistance, the underlying direct cell-cell communication mechanisms remain poorly understood. We identified horizontal mitochondrial transfer as a mechanism that enhances tumorigenesis in glioblastoma. This occurs primarily from brain-resident cells, including astrocytes, can be appreciated vitro vivo through intercellular connections between GBM cells non-malignant host cells. The acquisition of...
Abstract Glioblastoma (GBM), the most common primary brain cancer in adults1, is characterized by numerous cell-intrinsic/extrinsic interactions that drive tumorigenesis. In addition to cell-surface and secreted protein/extracellular vesicle interactions2,3, treatment resistance of GBM augmented formation cytoplasmic interconnections junctions among tumor cells4. These bridges cells enable exchange cellular metabolites as well mitochondria4, which can play a key role metabolic function...