A5101892218- Cancer Cells and Metastasis
- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Biochemical and Molecular Research
- Synthesis and biological activity
- 3D Printing in Biomedical Research
- Mathematical Biology Tumor Growth
- High Altitude and Hypoxia
- Breast Cancer Treatment Studies
- Synthesis and Catalytic Reactions
- Cancer Research and Treatments
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Cellular Mechanics and Interactions
- Bioinformatics and Genomic Networks
- HER2/EGFR in Cancer Research
- Nitric Oxide and Endothelin Effects
- Epigenetics and DNA Methylation
- Cardiovascular and exercise physiology
- Chromatin Remodeling and Cancer
- Nuclear Receptors and Signaling
- Climate Change and Health Impacts
Virginia Commonwealth University
2018-2025
University of Pittsburgh
2015-2019
Defence Institute of Physiology and Allied Sciences
2010-2011
Defence Research and Development Organisation
2011
Despite significant investments in cancer research and drug discovery/development, the rate of new approval is ≤5% most cases metastatic remain incurable. Ninety-five percent drugs fail clinical development because a lack therapeutic efficacy and/or unacceptable toxicity. One major factors responsible for low success anticancer failure preclinical models to adequately recapitulate complexity heterogeneity human cancer. For throughput capacity reasons, high-throughput screening growth...
Tumor size is strongly correlated with breast cancer metastasis and patient survival. Increased tumor contributes to hypoxic metabolic gradients in the solid an aggressive phenotype. Thus, it important develop three-dimensional (3D) models that recapitulate size-induced microenvironmental changes and, consequently, natural progression real time without use of artificial culture conditions or gene manipulations. Here, we developed size-controlled multicellular aggregates ("microtumors")...
Abstract Aim: Training under hypoxia has several advantages over normoxic training in terms of enhancing the physical performance. Therefore, we tested protective effect preconditioning by mimetic cobalt chloride against exercise‐induced oxidative damage skeletal muscles and improvement Method: Male Sprague–Dawley rats were randomly divided into four groups ( n = 8), namely control, cobalt‐supplemented, with training. The red gastrocnemius muscle was examined for all measurements, viz. free...
In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds receptors, leading important cancer signaling. However, the responsible for SphK1 activation has not yet been identified. Here, we demonstrate in triple-negative cells, which lack ERα66 but...
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the absence estrogen receptor, progesterone and HER2 expression. This lack targetable receptors makes TNBC particularly challenging to treat. Identifying therapeutic targets which can be targeted prevent recurrence crucial for developing better treatments. By studying mechanisms driving we hypothesized that post-therapy changes in cell epigenetics contribute using epigenetic drugs inhibit these could...
Abstract Epigenetics has established itself as a hallmark of cancer having essential roles in its initiation, establishment, and progression. Because their reversibility, epigenetics been aggressively targeted pharmacologically to correct abnormal biology the hopes reversing phenotypes. To develop novel epigenetic based therapeutic strategies for triple negative breast (TNBC) we combined loss function approaches (shRNA - KD, CAS9 KO, small molecule inhibitors) chromatin remolding protein...
The nucleosome remodeling factor (NURF) alters chromatin accessibility through interactions with its largest subunit,the bromodomain PHD finger transcription BPTF. BPTF is overexpressed in several cancers and an emerging anticancer target. Targeting the presents a potential strategy for inhibition evaluation of functional significance; however, inhibitor development has lagged behind those other bromodomains. Here we describe pyridazinone-based inhibitors. lead compound, BZ1, possesses high...
Progression to advanced stage metastatic disease, resistance endocrine therapies, and failure of drug combinations remain major barriers in the breast cancer therapy. Tumor microenvironments play an important role progression from non-invasive invasive disease as well response therapies. Development physiologically relevant, three-dimensional (3D) controlled that can reliably recapitulate tumor early will contribute our understanding biology serve a tool for screening regimens targeting...
Epigenetic regulators can modulate the effects of cancer therapeutics. To further these observations, we discovered that bromodomain PHD finger transcription factor subunit (BPTF) nucleosome remodeling (NURF) promotes resistance to doxorubicin, etoposide, and paclitaxel in 4T1 breast tumor cell line. BPTF functions promoting doxorubicin but not paclitaxel, may be selective cells, as a similar effect was observed embryonic stem cells. Sensitization etoposide with knockdown (KD) associated...
Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding the emergence impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over size, we recapitulated size-induced hypoxic microenvironment and in microtumors from epithelial breast cells patient-derived primary metastatic cancer cells, mesothelioma lung xenograft cells. The...
<p>MCF7 600 μm microtumor exhibit presence of Vimentin on the periphery and outer layer cells</p>
<p>MCF7 600 μm microtumor crawling out of the microwell</p>
<p>E-cad staining of 600 μm T47D microtumors migrating out the hydrogel microwells on day 6</p>
<p>Supplementary Materials and Methods</p>
<div>Abstract<p>Tumor size is strongly correlated with breast cancer metastasis and patient survival. Increased tumor contributes to hypoxic metabolic gradients in the solid an aggressive phenotype. Thus, it important develop three-dimensional (3D) models that recapitulate size-induced microenvironmental changes and, consequently, natural progression real time without use of artificial culture conditions or gene manipulations. Here, we developed size-controlled multicellular...
<div>Abstract<p>Tumor size is strongly correlated with breast cancer metastasis and patient survival. Increased tumor contributes to hypoxic metabolic gradients in the solid an aggressive phenotype. Thus, it important develop three-dimensional (3D) models that recapitulate size-induced microenvironmental changes and, consequently, natural progression real time without use of artificial culture conditions or gene manipulations. Here, we developed size-controlled multicellular...
<div>Abstract<p>Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding the emergence impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over size, we recapitulated size–induced hypoxic microenvironment and in microtumors from epithelial breast cells patient-derived primary metastatic cancer cells, mesothelioma...
<p>Supplementary video showing migration of a microtumor</p>
<p>Supplementary Information includes supplemental experimental procedures, description of gene regulatory network, two tables, eight figures and a supplementary video. Supplementary Table S1. List primers used S2. Parameters in the ODEs Figure S1: Large T47D microtumors exhibit collective migration, hypoxia aggressive phenotype. video showing migration microtumor S2: Treatment 150 600μm with conditioned media 150μm (150/CM). S3: Morphology multi-parameter flow cytometry on breast...
<p>Supplementary Information includes supplemental experimental procedures, description of gene regulatory network, two tables, eight figures and a supplementary video. Supplementary Table S1. List primers used S2. Parameters in the ODEs Figure S1: Large T47D microtumors exhibit collective migration, hypoxia aggressive phenotype. video showing migration microtumor S2: Treatment 150 600μm with conditioned media 150μm (150/CM). S3: Morphology multi-parameter flow cytometry on breast...
<div>Abstract<p>Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding the emergence impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over size, we recapitulated size–induced hypoxic microenvironment and in microtumors from epithelial breast cells patient-derived primary metastatic cancer cells, mesothelioma...