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Rosner, Marsha

One or more keywords matched the following properties of Rosner, Marsha

Property	Value
overview	Cancer is the second leading cause of death but, unlike heart disease, it has been a difficult disease to effectively understand or treat. The reason relates to the complexity and heterogeneity of the disease. Most tumors have complicated origins and are driven by rare mutations. Furthermore, different tissues have distinct cancers, individual tissues have multiple cancer subtypes, and tumors are composed of cells that are both genetically and phenotypically diverse. Thus, every tumor is unique and dynamic. The cause of lethality in most solid tumors such as breast cancer is the metastatic dissemination of tumor cells throughout the body. Metastasis is characterized by many distinct properties that are driven by changing stresses in the tumor microenvironment. Underlying all of these events are subcellular signaling pathways within tumor and environmental cells that are ultimately responsible for driving cells to a tumorigenic state. The current focus of my laboratory is to understand fundamental signaling mechanisms leading to the generation of tumor cells and their progression to metastatic disease, particularly in triple-negative breast cancer that lacks targeted therapies. We use systems level approaches including activity-based proteomics, RNAseq, ChIPseq, and mass spectrometry as well as computational, molecular, biophysical, cellular and mouse model-based methodologies to identify and characterize key regulators of tumor growth and metastasis. As an additional tool, we have utilized a specific physiological suppressor of metastasis, Raf Kinase Inhibitory Protein (RKIP or PEBP1), and a downstream target of RKIP in cells, BACH1, to identify both molecular and cellular mediators of metastasis. Our recent studies have shown that regulators of metastasis control multiple processes within the tumor cell microenvironment including metabolism, redox state, extracellular matrix, and recruitment and programming of tumor-associated macrophages. These factors also direct extracellular vesicles (exosomes) secreted by tumor cells to reprogram other cells in the body toward a pro-metastatic phenotype. Correlating omic-generated data from these studies with clinical data from cancer patients led to the identification of novel signaling modules that we used to build gene signatures that predict the metastatic potential of a tumor. More recently, our studies have led us to potential therapeutic treatments based on the concept of targeting key regulators of tumorigenesis, mimicking the action of metastasis suppressors such as RKIP or reprogramming signaling networks in cells to sensitize tumors to therapeutic agents.

Property

Value

overview

Cancer is the second leading cause of death but, unlike heart disease, it has been a difficult disease to effectively understand or treat. The reason relates to the complexity and heterogeneity of the disease. Most tumors have complicated origins and are driven by rare mutations. Furthermore, different tissues have distinct cancers, individual tissues have multiple cancer subtypes, and tumors are composed of cells that are both genetically and phenotypically diverse. Thus, every tumor is unique and dynamic. The cause of lethality in most solid tumors such as breast cancer is the metastatic dissemination of tumor cells throughout the body. Metastasis is characterized by many distinct properties that are driven by changing stresses in the tumor microenvironment. Underlying all of these events are subcellular signaling pathways within tumor and environmental cells that are ultimately responsible for driving cells to a tumorigenic state. The current focus of my laboratory is to understand fundamental signaling mechanisms leading to the generation of tumor cells and their progression to metastatic disease, particularly in triple-negative breast cancer that lacks targeted therapies. We use systems level approaches including activity-based proteomics, RNAseq, ChIPseq, and mass spectrometry as well as computational, molecular, biophysical, cellular and mouse model-based methodologies to identify and characterize key regulators of tumor growth and metastasis. As an additional tool, we have utilized a specific physiological suppressor of metastasis, Raf Kinase Inhibitory Protein (RKIP or PEBP1), and a downstream target of RKIP in cells, BACH1, to identify both molecular and cellular mediators of metastasis. Our recent studies have shown that regulators of metastasis control multiple processes within the tumor cell microenvironment including metabolism, redox state, extracellular matrix, and recruitment and programming of tumor-associated macrophages. These factors also direct extracellular vesicles (exosomes) secreted by tumor cells to reprogram other cells in the body toward a pro-metastatic phenotype. Correlating omic-generated data from these studies with clinical data from cancer patients led to the identification of novel signaling modules that we used to build gene signatures that predict the metastatic potential of a tumor. More recently, our studies have led us to potential therapeutic treatments based on the concept of targeting key regulators of tumorigenesis, mimicking the action of metastasis suppressors such as RKIP or reprogramming signaling networks in cells to sensitize tumors to therapeutic agents.

One or more keywords matched the following items that are connected to Rosner, Marsha

Item Type	Name
Concept	Androgen-Binding Protein
Concept	DNA-Binding Proteins
Concept	Insulin
Concept	Fibroblast Growth Factors
Concept	Insulin-Like Growth Factor I
Concept	Virulence Factors, Bordetella
Concept	Platelet-Derived Growth Factor
Concept	Nerve Growth Factors
Concept	Protein Binding
Concept	Transcription Factors
Concept	Receptor, Insulin
Concept	Time Factors
Concept	Tumor Necrosis Factor-alpha
Concept	Transforming Growth Factors
Concept	Guanine Nucleotide Exchange Factors
Concept	Transforming Growth Factor beta
Concept	Cyclic AMP Response Element-Binding Protein
Concept	RNA-Binding Proteins
Concept	Receptors, Tumor Necrosis Factor
Concept	Phosphatidylethanolamine Binding Protein
Concept	E2F Transcription Factors
Concept	Basic-Leucine Zipper Transcription Factors
Concept	Brain-Derived Neurotrophic Factor
Concept	ras Guanine Nucleotide Exchange Factors
Concept	Receptors, Tumor Necrosis Factor, Type I
Concept	Cell Growth Processes
Concept	rac GTP-Binding Proteins
Concept	rap1 GTP-Binding Proteins
Concept	Early Growth Response Protein 1
Concept	Tumor Necrosis Factors
Concept	Transforming Growth Factor alpha
Concept	Transcription Factor RelA
Concept	GTP-Binding Proteins
Concept	Serum Response Factor
Concept	Receptors, Tumor Necrosis Factor, Type II
Concept	Insulin Receptor Substrate Proteins
Concept	Vascular Endothelial Growth Factor A
Concept	Methyl-CpG-Binding Protein 2
Concept	Carrier Proteins
Concept	Epidermal Growth Factor
Concept	Growth Substances
Concept	Fibroblast Growth Factor 2
Concept	Receptors, Platelet-Derived Growth Factor
Concept	Telomere-Binding Proteins
Academic Article	Mutations in a zinc-binding domain of human insulin-degrading enzyme eliminate catalytic activity but not insulin binding.
Academic Article	Differentiation of central nervous system neuronal cells by fibroblast-derived growth factor requires at least two signaling pathways: roles for Ras and Src.
Academic Article	Raf, but not MEK or ERK, is sufficient for differentiation of hippocampal neuronal cells.
Academic Article	Insulin-degrading enzyme does not require peroxisomal localization for insulin degradation.
Academic Article	Extracellular signal-regulated kinase 7 (ERK7), a novel ERK with a C-terminal domain that regulates its activity, its cellular localization, and cell growth.
Academic Article	A novel mitogen-activated protein kinase is responsive to Raf and mediates growth factor specificity.
Academic Article	ERK8, a new member of the mitogen-activated protein kinase family.
Academic Article	Regulation of insulin degradation: expression of an evolutionarily conserved insulin-degrading enzyme increases degradation via an intracellular pathway.
Academic Article	Localization of the gene encoding insulin-degrading enzyme to human chromosome 10, bands q23----q25.
Academic Article	Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1.
Academic Article	The C-terminal domain of human insulin degrading enzyme is required for dimerization and substrate recognition.
Academic Article	Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mitogen-activated protein kinase.
Academic Article	A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.
Academic Article	Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.
Academic Article	Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism.
Academic Article	A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis.
Academic Article	Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands.
Academic Article	Sodium as a mediator of non-phorbol tumor promoter action. Down-modulation of the epidermal growth factor receptor by palytoxin.
Academic Article	Identification of novel metastasis suppressor signaling pathways for breast cancer.
Academic Article	Anthrax edema factor potency depends on mode of cell entry.
Academic Article	Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues.
Academic Article	Inducible expression and cellular localization of insulin-degrading enzyme in a stably transfected cell line.
Academic Article	Cloning and expression of the cDNA for a Drosophila insulin-degrading enzyme.
Academic Article	Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer.
Academic Article	Histamine antagonizes serotonin and growth factor-induced mitogen-activated protein kinase activation in bovine tracheal smooth muscle cells.
Academic Article	Functional analysis of conserved residues in the active site of insulin-degrading enzyme.
Academic Article	Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration.
Academic Article	The absence of NF-kappaB-mediated inhibition of c-Jun N-terminal kinase activation contributes to tumor necrosis factor alpha-induced apoptosis.
Academic Article	A novel interplay between Rap1 and PKA regulates induction of angiogenesis in prostate cancer.
Academic Article	Role of MAP kinase activation in bovine tracheal smooth muscle mitogenesis.
Academic Article	Identification of zinc ligands of the insulin-degrading enzyme.
Academic Article	Activation of MAP kinases by calcium-dependent and calcium-independent pathways. Stimulation by thapsigargin and epidermal growth factor.
Academic Article	Localization of immunoreactive epidermal growth factor receptor in neonatal and adult rat hippocampus.
Academic Article	Immortal rat hippocampal cell lines exhibit neuronal and glial lineages and neurotrophin gene expression.
Academic Article	An evolutionarily conserved TGF-alpha/insulin-degrading enzyme.
Academic Article	Palytoxin down-modulates the epidermal growth factor receptor through a sodium-dependent pathway.
Academic Article	Regulation of the epidermal growth factor receptor by growth-modulating agents: effects of staurosporine, a protein kinase inhibitor.
Academic Article	Regulation of insulin, epidermal growth factor, and transforming growth factor-alpha levels by growth factor-degrading enzymes.
Academic Article	Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites.
Academic Article	An insulin epidermal growth factor-binding protein from Drosophila has insulin-degrading activity.
Academic Article	Regulation of the epidermal growth factor receptor by growth-modulating agents.
Academic Article	Phosphorylation at threonine-654 is not required for negative regulation of the epidermal growth factor receptor by non-phorbol tumor promoters.
Academic Article	Regulation of epidermal growth factor receptor gene expression by retinoic acid and epidermal growth factor.
Academic Article	Basic and acidic fibroblast growth factors modulate the epidermal growth factor receptor by a protein kinase C-independent pathway.
Academic Article	Identification of a novel receptor in Drosophila for both epidermal growth factor and insulin.
Academic Article	Transforming growth factor-beta increases transcription of the genes encoding the epidermal growth factor receptor and fibronectin in normal rat kidney fibroblasts.
Academic Article	Thapsigargin, a novel promoter, phosphorylates the epidermal growth factor receptor at threonine 669.
Academic Article	Growth factors modify the epidermal growth factor receptor through multiple pathways.
Academic Article	Characterization of rodent epidermal growth factor receptor transcripts using a mouse genomic probe.
Academic Article	Decreased levels of hepatic epidermal growth factor receptors in obese hyperglycemic rodents.
Academic Article	Heterologous regulation of the epidermal growth factor receptor by palytoxin, a non-12-O-tetradecanoylphorbol-13-acetate-type tumor promoter.
Academic Article	Characterization of a Drosophila protein that binds both epidermal growth factor and insulin-related growth factors.
Academic Article	Isolation and characterization of an insulin-degrading enzyme from Drosophila melanogaster.
Academic Article	Tumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor.
Academic Article	Epidermal growth factor (EGF) receptor T669 peptide kinase from 3T3-L1 cells is an EGF-stimulated "MAP" kinase.
Academic Article	Temporal parameters of low energy laser irradiation for optimal delay of post-traumatic degeneration of rat optic nerve.
Academic Article	Two independent growth factor-generated signals regulate c-fos and c-myc mRNA levels in Swiss 3T3 cells.
Academic Article	Basic fibroblast-like growth factor is present in the conditioned medium of simian sarcoma virus transformed NRK cells.
Academic Article	WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis.
Academic Article	Activation of mitogen-activated protein kinase by epidermal growth factor in hippocampal neurons and neuronal cell lines.
Academic Article	Developmental regulation of an insulin-degrading enzyme from Drosophila melanogaster.
Academic Article	Growth state-dependent regulation of protein kinase C in normal and transformed murine cells.
Academic Article	Differential Raf requirement for activation of mitogen-activated protein kinase by growth factors, phorbol esters, and calcium.
Academic Article	Adenovirus and protein kinase C have distinct molecular requirements for regulating epidermal growth factor receptor trafficking.
Academic Article	Protein kinase Cdelta mediates neurogenic but not mitogenic activation of mitogen-activated protein kinase in neuronal cells.
Academic Article	Mitogen-activated protein kinase regulates the epidermal growth factor receptor through activation of a tyrosine phosphatase.
Academic Article	Insulin-like growth factor I receptor signaling in differentiation of neuronal H19-7 cells.
Academic Article	Induction of epidermal growth factor receptor gene transcription by transforming growth factor beta 1: association with loss of protein binding to a negative regulatory element.
Academic Article	Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation.
Academic Article	Functional human insulin-degrading enzyme can be expressed in bacteria.
Academic Article	Different protein kinase C isoforms determine growth factor specificity in neuronal cells.
Academic Article	Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein.
Academic Article	Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme.
Academic Article	Identification of an epidermal growth factor receptor transcriptional repressor.
Academic Article	Oxidative stress-mediated down-regulation of bcl-2 promoter in hippocampal neurons.
Academic Article	Role of threonine residues in regulation of the epidermal growth factor receptor by protein kinase C and mitogen-activated protein kinase.
Academic Article	Role of mitogen-activated protein kinase kinase in regulation of the epidermal growth factor receptor by protein kinase C.
Academic Article	Proteins interacting with the tuberous sclerosis gene products.
Academic Article	Insulin gene expression in immortalized rat hippocampal and pheochromocytoma-12 cell lines.
Academic Article	Raf kinase inhibitory protein regulates Raf-1 but not B-Raf kinase activation.
Academic Article	CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders.
Academic Article	A proline- and glutamine-rich protein promotes apoptosis in neuronal cells.
Academic Article	Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: correlation with tissue insulin levels.
Academic Article	Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations.
Academic Article	Identification of the cleavage sites of transforming growth factor alpha by insulin-degrading enzymes.
Academic Article	Role of cyclins in neuronal differentiation of immortalized hippocampal cells.
Academic Article	mTOR phosphorylated at S2448 binds to raptor and rictor.
Academic Article	Structural changes in intermediate filament networks alter the activity of insulin-degrading enzyme.
Academic Article	FGF induces a switch in death receptor pathways in neuronal cells.
Academic Article	Characterization of a Rac1 signaling pathway to cyclin D(1) expression in airway smooth muscle cells.
Academic Article	Regulation of airway smooth muscle cyclin D1 transcription by protein kinase C-delta.
Academic Article	Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas.
Academic Article	Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor.
Academic Article	Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7.
Academic Article	NF-kappaB is required for UV-induced JNK activation via induction of PKCdelta.
Academic Article	HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis.
Academic Article	Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint.
Academic Article	Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.
Academic Article	Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines.
Academic Article	Embryoid body formation of human amniotic fluid stem cells depends on mTOR.
Academic Article	RKIP regulates MAP kinase signaling in cells with defective B-Raf activity.
Academic Article	RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy.
Academic Article	An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.
Academic Article	Diacylglycerol modulates binding and phosphorylation of the epidermal growth factor receptor.
Academic Article	Cyclin D1 is required for S phase traversal in bovine tracheal myocytes.
Academic Article	Raf and fibroblast growth factor phosphorylate Elk1 and activate the serum response element of the immediate early gene pip92 by mitogen-activated protein kinase-independent as well as -dependent signaling pathways.
Academic Article	Purified recombinant insulin-degrading enzyme degrades amyloid beta-protein but does not promote its oligomerization.
Academic Article	Tuberin activates the proapoptotic molecule BAD.
Academic Article	An integrated view of cyclin E function and regulation.
Academic Article	A prognostic gene signature for metastasis-free survival of triple negative breast cancer patients.
Academic Article	RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2.
Academic Article	Network of mutually repressive metastasis regulators can promote cell heterogeneity and metastatic transitions.
Academic Article	RKIP structure drives its function: a three-state model for regulation of RKIP.
Academic Article	Retraction: Oct-3 is a maternal factor required for the first mouse embryonic division.
Academic Article	Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer.
Academic Article	Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal Populations.
Academic Article	Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages.
Academic Article	Gene expression in local stroma reflects breast tumor states and predicts patient outcome.
Academic Article	Insulin-Degrading Enzyme Does Not Require Peroxisomal Localization for Insulin Degradation.
Academic Article	Raf kinase inhibitor protein: lessons of a better way for ß-adrenergic receptor activation in the heart.
Academic Article	Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome.
Academic Article	Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism.
Academic Article	Limited inhibition of multiple nodes in a driver network blocks metastasis.
Academic Article	Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop.
Academic Article	SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1a/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells.
Concept	X-Box Binding Protein 1
Grant	Regulation of RKIP Function
Grant	Tumor-stromal interactions as targets of tumor metastasis suppressors
Grant	REGULATION OF PROTEIN KINASE C
Grant	Signaling Pathways in Neuronal Cells
Grant	CHARACTERIZATION OF A NOVEL MAP/ERK KINASE
Grant	Modulation of Head and Neck Cancer by Protein Kinase C
Grant	Role of Raf Kinase Inhibitory Protein in Prostate Cancer
Grant	Signaling Pathways in Neuronal Cells
Academic Article	Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.

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