- Ubiquitin and proteasome pathways
- Prostate Cancer Treatment and Research
- Microbial Metabolism and Applications
- Biofuel production and bioconversion
- Enzyme Production and Characterization
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- Computational Drug Discovery Methods
- RNA Interference and Gene Delivery
- Plant biochemistry and biosynthesis
- Protein Structure and Dynamics
- Plant-based Medicinal Research
- Genomics and Chromatin Dynamics
- Plant Pathogenic Bacteria Studies
- Microbial Metabolic Engineering and Bioproduction
- Diverse Scientific Research Studies
- RNA modifications and cancer
- Transgenic Plants and Applications
- Acne and Rosacea Treatments and Effects
- Lymphatic System and Diseases
- Pharmacological Effects of Natural Compounds
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Pneumonia and Respiratory Infections
Cedars-Sinai Medical Center
2020-2025
Norwegian Institute of Public Health
2024
University of California, Los Angeles
2021
Cancer Research UK
2013
Centre for Cellular and Molecular Biology
2007-2009
Council of Scientific and Industrial Research
2009
Abstract Despite progress in prostate cancer (PC) therapeutics, distant metastasis remains a major cause of morbidity and mortality from PC. Thus, there is growing recognition that preventing or delaying PC holds great potential for substantially improving patient outcomes. Here we show receptor-interacting protein kinase 2 (RIPK2) clinically actionable target inhibiting metastasis. RIPK2 amplified/gained ~65% lethal metastatic castration-resistant Its overexpression associated with disease...
Xanthomonas oryzae pv (Xoo) causes bacterial blight, a serious disease of rice (Oryza sativa). LipA is secretory virulence factor Xoo, implicated in degradation cell walls and the concomitant elicitation innate immune responses, such as callose deposition programmed death. Here, we present high-resolution structural characterization that reveals an all-helical ligand binding module distinct functional attachment to canonical hydrolase catalytic domain. We demonstrate enzyme binds glycoside...
Despite wide applications of CRISPR/Cas9 technology, effective approaches for CRISPR delivery with functional control are limited. In an attempt to develop a nanoscale CRSIPR/Cas9 platform, we discovered that several biocompatible polymers, including polymalic acid (PMLA), polyglutamic (PGA), and polyaspartic (PLD), when conjugated trileucine (LLL) moiety, can effectively inhibit Cas9 nuclease function. The inhibition by those polymers is dose-dependent, varying efficiency achieve 100%...
Abstract Ionizing radiation and chemotherapy deplete hematopoietic stem cells damage the vascular niche wherein reside. Hematopoietic cell regeneration requires signaling from an intact bone marrow (BM) niche, but mechanisms that control BM are poorly understood. We report endothelial secrete semaphorin 3 A (SEMA3A) in response to myeloablation SEMA3A induces p53 – mediated apoptosis via through its receptor, Neuropilin 1 (NRP1), activation of cyclin dependent kinase 5. Endothelial specific...
Abstract Acne is a dermatologic disease with strong pathologic association human commensal Cutibacterium acnes . Conspicuously, certain C. phylotypes are associated acne, whereas others healthy skin. Here we investigate if the evolution of enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by strains, HylA and HylB, demonstrate remarkable clinical correlation acne health. We show that strongly pro-inflammatory, HylB modestly anti-inflammatory in murine...
The planet earth is covered with 97% water, which largely found in the seas and oceans of planet. Marine diversity can become a huge scope for sources chemical drugs/compounds that are naturally obtained from variety marine population microorganisms to phytoplanktons animals like fish mollusks. Such extracted molecules researched studied their efficacy work against serious health issues cancer, HIV etc.
Abstract The CUT and homeodomain are ubiquitous DNA binding elements often tandemly arranged in multiple transcription factor families. However, how the work concertedly to bind remains unknown. Using ONECUT2, a driver therapeutic target of advanced prostate cancer, we show that while initiates binding, thermodynamically stabilizes ONECUT2-DNA complex through allosteric modulation CUT. We identify an arginine pair ONECUT family can adapt sequence variations. Base interactions by this...
Xanthomonas oryzae pv. is the causal agent of bacterial leaf blight, a serious disease rice. Several enzymes that are secreted through type II secretion system this bacterium play an important role in plant–microbe interaction, being for virulence and also able to induce potent host defence responses. One these secretory lipase/esterase, LipA, which shows very weak homology other lipases gives positive tributyrin plate assay. In study, LipA was purified from culture supernatant...
Introduction: Constitutive activation of NF-κB has been implicated as being contributive to cancer cell growth, drug resistance, and tumor recurrence in many cancers including breast cancer. Activation leads nuclear translocation RelA, a critical component the transcription factor complex, which subsequently binds specific DNA sites activates multitude genes involved diverse functions. Studies show that triple-negative (TNBC) cells possess constitutively active concomitantly have higher...
INTRODUCTION: Constitutive NFκB inflammatory signaling is a driving force of tumor progression, immune evasion, and therapeutic resistance in glioblastoma (GBM). CRL1101 novel small molecule inhibitor RelA (p65), transcription factor NFκB-mediated gene expression. Previously, we have shown that heptamethine carbocyanine (HMC) conjugated nanoparticles target GBM sites via organic anion transporter proteins. The activity has not been explored. Poor blood-brain barrier (BBB) penetration...
Abstract Transcription factors (TF) are essential determinants of gene regulation and their aberrant expression frequently drive cancers. The binding TFs to cognate DNA is central role in regulation. An understanding mechanism is, therefore, fundamental therapeutic relevance. Generally, bind through defined domains. CUT homeodomain two such evolutionarily conserved elements found paired multiple transcription factor families including ONECUT (OC), POU, CUX SATB. However, the cross-talk...
Viral infections have caused wide-scale suffering and death globally throughout the history, very recent being deadly Covid-19 infection. Many bacterial also result in various serious diseases. It is well known that microbial, especially viral are mainly transmitted between individuals through respiratory oral tract. Several chemicals based antimicrobial substances, like sanitizers disinfectants available to break this chain of transmission prevent development disease. But these some...
The ONECUT transcription factors feature a CUT and homeodomain, evolutionarily conserved elements that bind DNA cooperatively, but the process remains mechanistically enigmatic. Using an integrative binding analysis of ONECUT2, driver aggressive prostate cancer, we show homeodomain energetically stabilizes ONECUT2-DNA complex through allosteric modulation CUT. Further, base-interactions in both are necessary for favorable thermodynamics. We have identified novel arginine pair unique to...
Abstract Despite advances in diagnosis and treatment, metastatic prostate cancer remains incurable is associated with high mortality rates. Thus, novel actionable drug targets are urgently needed for therapeutic interventions advanced cancer. Here we report receptor-interacting protein kinase 2 (RIPK2) as an target suppressing metastasis. RIPK2 frequently amplified lethal cancers its overexpression disease progression aggressiveness. Genetic pharmacological inhibition of significantly...
Abstract Prostate cancer (PCa) is the most common and second lethal in men, claiming over 30,000 lives each year US alone. These PCa patient deaths are typically due to castration-resistant (CRPC) which resistant androgen deprivation therapy, receptor signaling inhibitors, chemotherapies. Our group others have shown that transcription factor ONECUT2 (OC2) a critical driver of CRPC. We discovered low molecular weight inhibitor OC2 (OC2i), known as CSRM617, inhibits metastatic cell culture...