A5088272548- Ubiquitin and proteasome pathways
- Chemotherapy-induced organ toxicity mitigation
- melanin and skin pigmentation
- Acute Lymphoblastic Leukemia research
- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Sphingolipid Metabolism and Signaling
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- T-cell and Retrovirus Studies
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Endoplasmic Reticulum Stress and Disease
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Autophagy in Disease and Therapy
- Acute Myeloid Leukemia Research
- Lipid Membrane Structure and Behavior
- Acute Kidney Injury Research
- Nanoplatforms for cancer theranostics
- NF-κB Signaling Pathways
University of Louisville
2016-2025
James Graham Brown Foundation
2014-2023
The Wistar Institute
2004-2023
University of Louisville Hospital
2020
Dartmouth College
2018
University of Chicago
2018
Kent State University
2018
Northwestern University
2018
Roswell Park Comprehensive Cancer Center
2018
Palmetto Hematology Oncology
2014
The acquisition of metastatic ability by tumor cells is considered a late event in the evolution malignant tumors. We report that untransformed mouse mammary have been engineered to express inducible oncogenic transgenes MYC and Kras(D12), or polyoma middle T, introduced into systemic circulation can bypass transformation at primary site develop pulmonary lesions upon immediate delayed oncogene induction. Therefore, previously may establish residence lung once they entered bloodstream assume...
AbstractRecent work with mouse models and human leukemic samples has shown that gain-of-function mutation(s) in Notch1 is a common genetic event T-cell acute lymphoblastic leukemia (T-ALL). The receptor signals through γ-secretase-dependent process releases intracellular from the membrane to nucleus, where it forms part of transcriptional activator complex. To identify target genes leukemia, we developed lines express doxycycline-dependent manner. Using gene expression profiling chromatin...
Direct communication between arteries and veins without intervening capillary beds is the primary pathology of arteriovenous malformations (AVMs). Although Notch signaling implicated in embryonic (AV) differentiation, its function adult mammalian vasculature has not been established due to lethality that often occurs both gain- loss-of-function mutants. We expressed a constitutively active Notch4 , int3 mouse endothelium by using tetracycline-repressible system suppress during embryogenesis....
Cisplatin, a chemotherapeutic used for the treatment of solid cancers, has nephrotoxic side effects leading to acute kidney injury (AKI). Cisplatin cannot be given patients that have comorbidities predispose them an increased risk AKI. Even without these comorbidities, 30% administered cisplatin will develop injury, requiring oncologist withhold or reduce next dose, less effective therapeutic regimen. Although recovery can occur after one episode cisplatin-induced AKI, longitudinal studies...
Nucleotide synthesis is essential to proliferating cells, but the preferred precursors for de novo biosynthesis are not defined in human cancer tissues. We have employed multiplexed stable isotope-resolved metabolomics track metabolism of [13C6]glucose, D2-glycine, [13C2]glycine, and D3-serine into purine nucleotides freshly resected cancerous matched noncancerous lung tissues from nonsmall cell (NSCLC) patients, we compared with established NSCLC PC9 A549 lines vitro Surprisingly,...
Abstract Aberrant Notch signaling contributes to more than half of all human T-cell leukemias, and accumulating evidence indicates involvement in other neoplasms. We developed a tetracycline-inducible mouse model (Top-Notchic) examine the genetic interactions underlying development Notch-induced neoplastic disease. Using this model, we show that suppresses p53 lymphomagenesis through repression ARF-mdm2-p53 tumor surveillance network. Attenuation expression resulted dramatic increase levels...
Most, if not all, cancers are composed of cells in which more than one gene has a cancer-promoting mutation. Although recent evidence shown the benefits therapies targeting single mutant protein, little attention been given to situations experimental tumors induced by multiple cooperating oncogenes. Using combinations doxycycline-inducible and constitutive Myc Kras transgenes expressed mouse mammary glands, we show that cooperative actions two oncogenes remain dependent on activity oncogene....
The importance of mitogen-activated protein kinase signaling in melanoma is underscored by the prevalence activating mutations N-Ras and B-Raf, yet clinical development inhibitors this pathway has been largely ineffective, suggesting that alternative oncogenes may also promote melanoma. Notch an interesting candidate only correlated with progression; a thorough assessment tumor-initiating effects activated on human melanocytes would clarify mounting correlative evidence perhaps identify...
Cisplatin is used to treat many solid cancers, but its dose-limiting side effect nephrotoxicity, causing acute kidney injury in 30% of patients. Previously, we have developed a mouse model that better recapitulates the cisplatin dosing regimen humans receive and found repeated induces interstitial renal fibrosis. Chronic disease progressive characterized by chronic inflammation, worsening fibrosis, development glomerulosclerosis, endothelial dysfunction. To determine if damage caused results...
JAGGED1 is a member of the Delta/Serrate/Lag-2 (DSL) family proteins that are cell-bound ligands for Notch receptors. Initiation signaling occurs through series proteolytic events upon binding to DSL protein presented on neighboring cells. Whether themselves capable initiating an intrinsic mechanism within cell they expressed not known. Aberrant misexpression and DELTA1 has been documented in several human tumors; however, by which contributes oncogenesis elucidated. We report expression...
We have previously shown that all six members of the anti-apoptotic BCL2 gene family can cooperate with (myelocytomatosis oncogene) MYC in a mouse model leukemia, but three them are significantly less potent contributors to leukemogenicity than other three. The protein encoded by one these genes, BCL2L10/BCLb, was recently vary dramatically many primary human cancers immunohistochemistry, and levels were inversely correlated survival patients several cancer types. examined BCLb mRNA panel...
// Parag P. Shah 1 , Tess V. Dupre 2 Leah J. Siskind Levi Beverly 1, 2, 3 James Graham Brown Cancer Center, University of Louisville, KY 40202, USA Department Pharmacology and Toxicology, Louisville School Medicine, Division Hematology Oncology, Correspondence to: Beverly, email: Levi.Beverly@Louisville.edu Keywords: ER stress, chemotherapeutics, EMT, migration, invasion Received: October 24, 2016 Accepted: January 2017 Published: February 07, ABSTRACT Endoplasmic reticulum (ER) in...
Determining mechanistic details about how drugs kill cancer cells is critical for predicting which cancers will respond to given therapeutic regimens and identifying effective combinations of that more potently while sparing normal cells. The BCL2 family proteins bioactive sphingolipids are intricately linked during apoptotic cell death. In fact, many chemotherapeutic known cause accumulation the pro-apoptotic sphingolipid ceramide; however, mechanism by this occurs not completely...
There are five Ubiquilin proteins (UBQLN1-4, UBQLN-L), which evolutionarily conserved and structurally similar. UBQLN have three functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated (UBA), STI chaperone-like regions in the middle. Alterations UBQLN1 gene been detected a variety of disorders ranging from Alzheimer's disease to cancer. has largely studied neurodegenerative context protein quality control. Several studies hypothesized that UBA binds...
Acute kidney injury (AKI), resulting from chemotherapeutic agents such as cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves apoptotic and necrotic cell death, pathways regulated by sphingolipids ceramide glucosylceramide. Results this study indicate that C57BL/6J mice treated with cisplatin had increased hexosylceramide levels renal cortex 72 h following treatment. Pretreatment inhibitors acid sphingomyelinase de novo synthesis (amitriptyline myriocin,...
// Parag P. Shah 1 and Levi J. Beverly 1,2,3 James Graham Brown Cancer Center, University of Louisville, KY, USA 2 Department Medicine, Division Hematology Oncology, Louisville School 3 Pharmacology Toxicology, Correspondence to: Beverly, email: Keywords : ER stress, p97, ERAD, EMT, migration, invasion, metastasis Received February 06, 2015 Accepted April 08, Published 23, Abstract Valosin-containing protein (VCP), also called is a AAA+ ATPase that has been shown to be involved in...
// Kumar Saurabh 1,* , Michael T. Scherzer 1,4,* Parag P. Shah 1 Alice S. Mims 5 William W. Lockwood 6 Andrew Kraft and Levi J. Beverly 1,2,3,4 James Graham Brown Cancer Center, University of Louisville, KY 2 Department Medicine, Division Hematology Oncology, Louisville School 3 Pharmacology Toxicology, 4 Bioengineering, J.B Speed Engineering, Hollings Medical South Carolina, Charleston, SC Integrative British Columbia Agency, Vancouver, Columbia, Canada * These authors contributed equally...
Poor survival rates from lung cancer can largely be attributed to metastatic cells that invade and spread throughout the body. The tumor microenvironment (TME) is composed of multiple cell types, as well non-cellular components. TME plays a critical role in development cancers by providing migratory cues changing properties cells. Extracellular Matrix (ECM), main component TME, has been shown change composition during progression, contributing invasion away primary site. Although ECM...
C57BL/6 mice are one of the most commonly used mouse strains in research, especially kidney injury studies. However, resistant to chronic disease-associated pathologies, particularly development glomerulosclerosis and interstitial fibrosis. Our laboratory others developed a more clinically relevant dosing regimen cisplatin (7 mg/kg once week for 4 wk euthanized at day 24) that leads progressive fibrosis FVB/n mice. we found treating with this same does not result In study, demonstrated...