A5069409771- IL-33, ST2, and ILC Pathways
- Cytomegalovirus and herpesvirus research
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Metabolism and Genetic Disorders
- Wnt/β-catenin signaling in development and cancer
- T-cell and B-cell Immunology
- Pulmonary Hypertension Research and Treatments
- Toxoplasma gondii Research Studies
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- Adenosine and Purinergic Signaling
- Advanced Glycation End Products research
- Lung Cancer Treatments and Mutations
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Ion Transport and Channel Regulation
- interferon and immune responses
- Organ Donation and Transplantation
- Cancer, Hypoxia, and Metabolism
- Calcium signaling and nucleotide metabolism
- Cancer Genomics and Diagnostics
- Acute Kidney Injury Research
- Cancer, Stress, Anesthesia, and Immune Response
Johns Hopkins Medicine
2013-2025
Johns Hopkins University
2013-2025
University of Virginia
2019-2024
GlaxoSmithKline (United States)
2024
Charlottesville Medical Research
2021
Hampton University
2015-2020
Center for Neuroscience and Regenerative Medicine
2020
Infection with human cytomegalovirus (HCMV) is a threat for pregnant women and immunocompromised hosts. Although limited drugs are available, development of new agents against HCMV desired. Through screening the LOPAC library, we identified emetine as inhibitor. Additional studies confirmed its anti-HCMV activities in foreskin fibroblasts: EC50−40±1.72 nM, CC50−8±0.56 μM, selectivity index 200. inhibition occurred after virus entry, but before DNA replication, resulted decreased expression...
ABSTRACT Pulmonary fibrosis is a progressive lung disease hallmarked by increased fibroblast proliferation, amplified levels of extracellular matrix deposition and angiogenesis. Although dysregulation angiogenic mediators has been implicated in pulmonary fibrosis, the specific rate‐limiting markers involved their role progression remains unclear. We demonstrate that bleomycin treatment induces angiogenesis, inhibition central mediator VEGF using anti‐VEGF antibody CBO‐P11 significantly...
Conventional therapy for human cytomegalovirus (CMV) relies on inhibition of the viral DNA polymerase. Ganciclovir (GCV) is first-line therapy, but when GCV-resistant strains emerge, alternative therapies are extremely limited and associated with significant toxicities. Combination anti-CMV agents that act different targets or stages virus replication has not been well studied, mostly because number agents. We report our investigation combinations inhibit CMV by targeting polymerase,...
ABSTRACT Infection with human cytomegalovirus (HCMV) continues to be a threat for pregnant women and immunocompromised hosts. Although limited anti-HCMV therapies are available, development of new agents is desired. The Wnt signaling pathway plays critical role in embryonic cancer stem cell targeted by gammaherpesviruses, Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV). HCMV infects cells, including neural progenitor during embryogenesis. To investigate the...
Cardiac glycosides are potent inhibitors of cancer cell growth and possess antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity digitoxin several its analogues. We show that sugar type length attached to steroid core structure affects activity. Structure–activity relationship (SAR) studies identified l-sugar containing cardiac as having improved anti-CMV may lead better understanding how these compounds inhibit CMV replication.
Lung cancer is a leading cause of cancer‐related death in the United States. Although several drugs have been developed that target individual biomarkers, their success has limited due to intrinsic or acquired resistance for specific targets such drugs. A more effective approach multiple pathways dictate progression. Cardiac glycosides demonstrate multimodal effects on cell survival, and our aim was evaluate effect two naturally occurring monosaccaridic cardiac glycosides—Convallatoxin...
ABSTRACT Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report a novel pathway used by cardiac glycosides to HCMV replication: induction AMP-activated protein kinase (AMPK) activity and autophagy flux through the Na + ,K /ATPase α1 subunit. Our data illustrate an intricate balance between regulators AMPK, mammalian target rapamycin (mTOR), ULK1 during infection treatment with glycoside digitoxin. Both digitoxin...
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with life expectancy of less than 5 years post diagnosis for most patients. Poor molecular characterization IPF has led to insufficient understanding the pathogenesis disease, resulting in lack effective therapies. In this study, we have integrated label-free LC-MS based approach systems biology identify signaling pathways and regulatory nodes within protein interaction networks that govern phenotypic changes may lead IPF....
Cardiac glycosides (CGs), historically used to treat heart failure and arrhythmias, bind the α subunit of Na+/K+-ATPase pump inhibit its activity. Their anticancer antiviral activities are interest. The has four isoforms (α1–4), each with unique tissue distribution expression pattern; their contributions have not been studied. We previously reported that CGs human CMV (HCMV) in vitro but mouse (MCMV). In addition low affinity α1 for CGs, we hypothesized other contribute anti-CMV CGs. show...
We report that the artemisinin-derived dimer diphenyl phosphate (DPP; 838) is most selective inhibitor of human cytomegalovirus (CMV) replication among a series monomers and dimers. Dimer 838 was also unique in being an irreversible CMV inhibitor. The peroxide unit within artemisinins' chemical structures critical to their activities, its absence results loss anti-CMV activities. Surprisingly, deoxy retained modest activity, suggesting DPP moiety contributes alone did not inhibit...
Autoimmunity can result when cells fail to properly dispose of DNA. Mutations in the three-prime repair exonuclease 1 (TREX1) cause a spectrum human autoimmune diseases resembling systemic lupus erythematosus. The cytosolic dsDNA sensor, cyclic GMP-AMP synthase (cGAS), and stimulator IFN genes (STING) are required for pathogenesis, but specific which DNA sensing subsequent type I (IFN-I) production occur remain elusive. In this study, we demonstrate that TREX1 D18N catalytic deficiency...
Like with most solid tumors, the presence of a subpopulation cancer stem cells (CSCs) or stem‐like (CS‐LCs) has been associated chemoresistance and tumor relapse in lung cells. In absence serum, CSCs/CS‐LCs have ability to grow as tumorspheres (LTSs), this system is routinely used for isolation characterization putative CSCs/CS‐LCs. Methods isolate LTSs are usually performed serum‐free media supplemented specific additives such epidermal growth factor basic fibroblast factor. study, we...
Key Points IL-33/ST2 alarmin pathway regulates inflammation, fibrosis, and resolution of ischemia-reperfusion injury kidneys. ST2 the transcriptome T-regulatory cells related to suppressive reparative functions. The secretome + hypoxic in an amphiregulin-dependent manner. Background Inflammation is a major cause kidney injury. IL-1 family cytokine IL-33 released from damaged modulates immune response through its receptor expressed on many cell types, including regulatory T (Tregs). Although...
While there are targeted treatments for triple positive breast cancers, lack of specific biomarkers triple-negative cancers (TNBC) has hindered the development therapies this subset cancers. In study, we evaluated anticancer properties cardiac glycoside Digitoxin (Dtx) and its synthetic analog MonoD on cancer cell lines MCF-7 (estrogen receptor-positive cancer) MDA-MB-468 (triple-negative cancer). Both glycosides, at concentrations within therapeutic range, increased fraction cells in G0/G1...
Cellular oxidative stress is implicated not only in lung injury but also contributing to the development of pulmonary fibrosis. We demonstrate that a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly inhibited bleomycin-induced fibrogenic effects both vitro vivo. Further investigation into underlying mechanisms revealed MnTBAP targets canonical Wnt non-canonical Wnt/Ca2+ signaling...
The Three Prime Repair EXonuclease I (TREX1) is critical for degrading post-apoptosis DNA. Mice expressing catalytically inactive TREX1 (TREX1 D18N) develop lupus-like autoimmunity due to chronic sensing of undegraded DNA substrates, production the inflammatory cytokines, and inappropriate activation innate adaptive immunity. This study aimed investigate Thelper (Th) dysregulation in D18N model system as a potential mechanism autoimmunity. Comparison immune cells secondary lymphoid organs,...
The efficacy of chemotherapy is hindered by both tumor heterogeneity and acquired or intrinsic multi-drug resistance caused the contribution multidrug proteins stemness-associated prosurvival markers. Therefore, targeting resistant cells would be much more effective against cancer. In this study, we characterized chemoresistance properties adherent (anchorage-dependent) lung H460 breast MCF-7 cancer growing under prolonged periods serum starvation (PPSS). We found that PPSS, cell lines were...
Abstract Background: Digitoxin, a cardiac glycoside had shown considerable promise as an anti-cancer therapeutic. However, doses of digitoxin required to inhibit cancer cell proliferation lead cardiotoxic side effects. We have previously that novel analog digitoxin, MonoD, activates apoptosis in human lung cells at much lower concentrations compared digitoxin. postulate treatment with MonoD leads distinct metabolic signatures on which will help delineate the pathways dictate action....
Abstract Purpose: Breast cancer is the second most common type of in women and several drugs are currently being used against this disease. In spite availability promising chemotherapeutic drugs, it often observed that tumor cells develop resistance to these rendering them ineffective after prolonged use. Identifying alternative effective treatment options thus crucial improve life expectancy breast patients. Resveratrol, a dietary agent considered as potential drug candidate due its...