A5085384735- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Telomeres, Telomerase, and Senescence
- Virus-based gene therapy research
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
- Mechanisms of cancer metastasis
- Bone health and treatments
- Bone and Dental Protein Studies
- Phagocytosis and Immune Regulation
- Nanoplatforms for cancer theranostics
- Drug Transport and Resistance Mechanisms
- Hematopoietic Stem Cell Transplantation
- Biomarkers in Disease Mechanisms
- Immunotherapy and Immune Responses
- bioluminescence and chemiluminescence research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Medical Imaging Techniques and Applications
- Chemokine receptors and signaling
- Crystallization and Solubility Studies
- Pharmacological Effects and Toxicity Studies
- Cell Adhesion Molecules Research
Washington University in St. Louis
2015-2025
Trinity Washington University
2024
The University of Texas Southwestern Medical Center
2024
Southwestern Medical Center
2024
Mallinckrodt (United States)
2008-2022
Imaging Center
2006-2022
Optica
2017
Research Institute for Genetic and Human Therapy
2013
Molecular Oncology (United States)
2012
University of Luxembourg
2011
The chemokine receptor CXCR4 and its cognate ligand CXCL12 recently have been proposed to regulate the directional trafficking invasion of breast cancer cells sites metastases. However, effects on growth primary tumors established metastases survival not determined. We used stable RNAi reduce expression in murine 4T1 cells, a highly metastatic mammary cell line that is model for stage IV human cancer. Using noninvasive bioluminescence magnetic resonance imaging, we showed knockdown...
The Wnt/β-catenin signaling pathway is activated in breast cancer, a leading cause of cancer mortality women. Because mutations the key intracellular components this are rare, identifying molecular mechanisms aberrant Wnt activation critical for development pathway-targeted therapy. Here, we show that expression coreceptor LRP6 up-regulated subpopulation human cancers. silencing cells reduces signaling, cell proliferation, and vivo tumor growth. In administration an antagonist, Mesd,...
Abstract Age is a major risk factor for the development of cancer. Senescent fibroblasts, which accumulate with age, secrete protumorigenic factors collectively referred to as senescence-associated secretory phenotype (SASP). Here, we examined molecular mechanisms that control SASP activation, focusing on known osteopontin (OPN). We found expression canonical members interleukin (IL)-6 and IL-8, but not OPN, were dependent upon persistent DNA damage response (DDR) evidenced by ATM NF-κB...
Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute neoplastic progression. The importance of progression is underscored by studies showing that fibroblasts isolated from a tumor stimulate growth preneoplastic and cells xenograft models. Similarly, senescent promote vitro vivo. Because accumulate age, their presence hypothesized facilitate formation older individuals. To identify stromal factors directly responsible for stimulating...
ABSTRACT Mouse models of herpes simplex virus type 1 (HSV-1) infection provide significant insights into viral and host genes that regulate disease pathogenesis, but conventional methods to determine the full extent spread replication typically require sacrifice infected animals. To develop a noninvasive method for detecting HSV-1 in living mice, we used strain KOS recombinant expresses firefly ( Photinus pyralis ) Renilla reniformis luciferase reporter proteins monitored with cooled...
Coelenterazine is widely distributed among marine organisms, producing bioluminescence by calcium-insensitive oxidation mediated Renilla luciferase (Rluc) and calcium-dependent the photoprotein aequorin. Despite its abundance in nature wide use of both proteins as reporters gene expression signal transduction, little known about mechanisms coelenterazine transport cell permeation. Interestingly, analogues share structural physiochemical properties compounds transported multidrug resistance...
Behavioral and physiological circadian rhythms in mammals are controlled by a master pacemaker the hypothalamic suprachiasmatic nuclei (SCN). Recently, oscillations of hormone secretion, clock gene expression, electrical activity have been demonstrated explants other brain regions. This suggests that some extra-SCN regions contain functional, SCN-independent clock, but vivo evidence for intrinsic pacemaking is still lacking. We developed novel method to image bioluminescence from main...
Abstract Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and contact-facilitated nanomicelle technology enabled highly selective delivery co-localization titanocene radiolabelled...
Despite improvement in treatment options for myeloma patients, including targeted immunotherapies, multiple remains a mostly incurable malignancy. High CS1 (SLAMF7) expression on cells and limited normal makes it promising target CAR-T therapy. The protein has two extracellular domains - the distal Variable (V) domain proximal Constant 2 (C2) domain. We generated tested CS1-CAR-T targeting V of (Luc90-CS1-CAR-T) demonstrated anti-myeloma killing vitro vivo using mouse models. Since...
ABSTRACT Herpes simplex virus type 1 (HSV-1) can produce disseminated, systemic infection in neonates and patients with AIDS or other immunocompromising diseases, resulting significant morbidity mortality spite of antiviral therapy. Components host immunity that normally limit HSV-1 to localized epithelial neuronal remain incompletely defined. We used vivo bioluminescence imaging determine effects I II interferons (IFNs) on replication tropism mice genetic deficiency I, II, both IFN...
Membrane permeation peptides, such as Tat basic domain, have emerged useful membrane transduction agents with potential utility in therapeutic delivery and diagnostic imaging. While generally thought to universally permeate all cells by a nonselective process, the mechanism of remains poorly characterized. To examine vectorial transport properties domain well-differentiated epithelial possessing tight junctions, l d stereoisomers Tat48-57 peptide conjugates labeled 99mTc were quantitatively...
Abstract Multidrug resistance (MDR) remains a major obstacle to successful chemotherapeutic treatment of cancer and can be caused by overexpression P-glycoprotein, the MDR1 gene product. To further validate knockdown approach for circumventing MDR, we developed P-glycoprotein inhibition strategy using short hairpin RNA interference (shRNAi) now show efficacy target specificity in vivo. Two eight tested shRNAi constructs targeted against human mRNA inhibited expression >90%, whereas...
Apoptosis is an important process involved in diverse developmental pathways, homeostasis, and response to therapy for a variety of diseases. Thus, noninvasive methods study regulation monitor cell death cells whole animals are desired. To specifically detect apoptosis vivo, novel cell-permeable activatable caspase substrate, TcapQ647, was synthesized Km, kcat, Ki values were biochemically characterized. Specific cleavage TcapQ647 by effector caspases demonstrated using panel purified...
CD47, also called integrin-associated protein, plays a critical role in the innate immune response and is an atypical member of immunoglobulin superfamily that interacts with activates beta3 integrins. integrin(-/-) mice have defective platelet osteoclast function are protected from bone metastasis. The CD47 skeletal homeostasis metastasis has not been described. CD47(-/-) had increased mass vivo. Although number functional osteoclasts formed by differentiating marrow macrophages was...
Hedgehog (Hh) signaling is implicated in bone development and cellular transformation. Here we show that inhibition of Hh pathway activity inhibits tumor growth through effects on the microenvironment. Pharmacologic effector Smoothened (Smo) increased trabecular vivo inhibited osteoclastogenesis vitro. In addition, enhanced due to heterozygosity inhibitory receptor Patched (Ptch1(+/-)) resorption, suggesting direct regulation osteoclast (OC) by pathway. Ptch1(+/-) mice had metastatic...
Nanogels are attractive biocompatible materials that enable local delivery of multiple drugs. In this study, we demonstrated 3D printing technology could be used to precisely construct nanogel discs carrying paclitaxel and rapamycin. 3D-printed disc rounds (12 mm diameter × 1 thickness) rapamycin evaded premature gelation during storage the initial burst release drugs in dissolution medium. vivo permitted successful intraperitoneal ES-2-luc ovarian-cancer-bearing xenograft mice. They were...
Abstract In metastatic breast cancer, HER2-activating mutations frequently co-occur with in PIK3CA, TP53, or CDH1. Of these co-occurring mutations, HER2 and PIK3CA are the most commonly comutated gene pair, approximately 40% of HER2-mutated cancers also having activating PIK3CA. To study effects we generated genetically engineered mice HER2V777L; PIK3CAH1047R transgenes (HP mice) studied resulting both vivo as well ex using cancer organoids. HP showed accelerated tumor formation increased...
To enable concurrent whole body scintigraphy and direct imaging of subcellular localization permeation peptides, dual-labeled Tat-peptides useful for both radiometric analysis fluorescence microscopy are desired molecular applications. Thus, novel D-Tat-peptides comprising Tat-basic domain (hgrkkrrqrrrgc), C-terminus conjugated with fluorescein-5-maleimide (FM) N-terminus chelated [99mTc(CO)3] via histidine coordination, were synthesized characterized. In human Jurkat cells, radiotracer...
Obesity is a major factor central to the development of insulin resistance and type 2 diabetes. The identification characterization genes involved in regulation adiposity, sensitivity, glucose uptake are key design new drug therapies for this disease. In study, we show that polarity kinase Par-1b/MARK2 required regulating metabolism vivo . Mice null Par-1b were lean, hypersensitive, resistant high-fat diet-induced weight gain, hypermetabolic. 18 F-FDG microPET hyperinsulinemic–euglycemic...