Browsing by Author "Frank, David"
Now showing items 1-19 of 19
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A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation
Nelson, Erik A.; Sharma, Sreenath V.; Settleman, Jeffrey; Frank, David Alan (Impact Journals LLC, 2011)STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under ... -
Cooperation of imipramine blue and tyrosine kinase blockade demonstrates activity against chronic myeloid leukemia
Laidlaw, Kamilla M.E.; Berhan, Samuel; Liu, Suhu; Silvestri, Giovannino; Holyoake, Tessa L.; Frank, David A.; Aggarwal, Bharat; Bonner, Michael Y.; Perrotti, Danilo; Jørgensen, Heather G.; Arbiser, Jack L. (Impact Journals LLC, 2016)The use of tyrosine kinase inhibitors (TKI), including nilotinib, has revolutionized the treatment of chronic myeloid leukemia (CML). However current unmet clinical needs include combating activation of additional survival ... -
Deregulation of SOCS5 suppresses dendritic cell function in chronic lymphocytic leukemia
Toniolo, Patricia A.; Liu, Suhu; Yeh, Jennifer E.; Ye, Darwin Q.; Barbuto, José Alexandre M.; Frank, David A. (Impact Journals LLC, 2016)One cause of morbidity and mortality in chronic lymphocytic leukemia (CLL) is infection, which results from defects in a number of components of the immune system. In particular, dendritic cells (DCs) are functionally ... -
Estrogen Signaling in Breast Tumorigenesis
Chi, David (2016-09-09)The estrogen receptor (ER) is expressed in approximately 70% of sporadic breast cancers and is believed to activate genes driving tumorigenesis and initial cell proliferation. Therapeutic targeting of the ER signaling ... -
Evolving Models of Ovarian Cancer: Defining the Role of PAX8 in Fallopian Tube Tumorigenesis
Emori, Megan Marie (2015-08-07)Ovarian cancer is the most deadly gynecological malignancy in the US. Once thought to be a single disease arising from the ovarian surface epithelium, we now understand that it is in fact a heterogenous disease with origins ... -
Granulin, a novel STAT3-interacting protein, enhances STAT3 transcriptional function and correlates with poorer prognosis in breast cancer
Yeh, Jennifer E.; Kreimer, Simion; Walker, Sarah R.; Emori, Megan M.; Krystal, Hannah; Richardson, Andrea; Ivanov, Alexander R.; Frank, David A. (Impact Journals LLC, 2015)Since the neoplastic phenotype of a cell is largely driven by aberrant gene expression patterns, increasing attention has been focused on transcription factors that regulate critical mediators of tumorigenesis such as ... -
JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
Yeh, Jennifer E; Toniolo, Patricia A; Frank, David A (Landes Bioscience, 2013)A recent article published by Britschgi et al. in Cancer Cell, “JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer,” describes a ... -
NTRK2 activation cooperates with PTEN deficiency in T-ALL through activation of both the PI3K–AKT and JAK–STAT3 pathways
Yuzugullu, Haluk; Von, Thanh; Thorpe, Lauren M; Walker, Sarah R; Roberts, Thomas M; Frank, David A; Zhao, Jean J (Nature Publishing Group, 2016)Loss of PTEN, a negative regulator of the phosphoinositide 3-kinase signaling pathway, is a frequent event in T-cell acute lymphoblastic leukemia, suggesting the importance of phosphoinositide 3-kinase activity in this ... -
Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
Chen, Tzu-Hsiu; Feng, Whei; Jänne, Pasi A; Alvarez, James V; Zappaterra, Mauro; Bulmer, Sara E; Sellers, William R; Greulich, Heidi E.; Frank, David Alan; Hahn, William C.; Meyerson, Matthew Langer (Public Library of Science, 2005)Background: Somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor sensitivity to the ... -
Physiological and Pharmacological Regulation of the STAT3 Pathway in Cancer
Xiang, Michael (2013-10-18)STAT3 is a critical oncogenic transcription factor, but how it becomes aberrantly activated in cancer is unclear. We have discovered a new pathway whose loss is associated with persistent STAT3 activation in human cancer. ... -
Screening approaches to generating STAT inhibitors: Allowing the hits to identify the targets
Walker, Sarah R.; Frank, David A. (Landes Bioscience, 2012)STAT transcription factors are regulators of critical cellular processes such as proliferation, survival, and self-renewal. While the activity of these proteins is tightly regulated under physiological conditions, they can ... -
STAT signaling in the pathogenesis and treatment of myeloid malignancies
Bar-Natan, Michal; Nelson, Erik A.; Xiang, Michael; Frank, David A. (Landes Bioscience, 2012)STAT transcription factors play a critical role in mediating the effects of cytokines on myeloid cells. As STAT target genes control key processes such as survival, proliferation and self-renewal, it is not surprising that ... -
STAT3 Activity and Function in Cancer: Modulation by STAT5 and miR-146b
Walker, Sarah R.; Xiang, Michael; Frank, David A. (MDPI, 2014)The transcription factor STAT3 regulates genes that control critical cellular processes such as proliferation, survival, pluripotency, and motility. Thus, under physiological conditions, the transcriptional function of ... -
A STAT3 Gene Expression Signature in Gliomas is Associated with a Poor Prognosis
Alvarez, James V.; Mukherjee, Neelanjan; Chakravarti, Arnab; Robe, Pierre; Zhai, Gary; Chakladar, Abhijit; Loeffler, Jay S; Black, Peter McLaren; Frank, David A. (Libertas Academica, 2007)Gliomas frequently display constitutive activation of the transcription factor STAT3, a protein that is known to be able to mediate neoplastic transformation. STAT3 regulates genes that play a central role in cellular ... -
STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF- B to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes
Xiang, Michael; Birkbak, Nicolai Juul; Vafaizadeh, V.; Walker, Sarah Rebecca; Yeh, Jennifer E; Liu, Suhu; Kroll, Yasmin; Boldin, M.; Taganov, K.; Groner, B.; Richardson, Andrea Lynn; Frank, David Alan (American Association for the Advancement of Science (AAAS), 2014)Interleukin-6 (IL-6)–mediated activation of signal transducer and activator of transcription 3 (STAT3) is a mechanism by which chronic inflammation can contribute to cancer and is a common oncogenic event. We discovered a ... -
STAT5 Outcompetes STAT3 To Regulate the Expression of the Oncogenic Transcriptional Modulator BCL6
Walker, Sarah Rebecca; Nelson, E; Yeh, Jennifer E; Pinello, Luca; Yuan, Guocheng; Frank, David Alan (American Society for Microbiology, 2013)Inappropriate activation of the transcription factors STAT3 and STAT5 has been shown to drive cancer pathogenesis through dysregulation of genes involved in cell survival, growth, and differentiation. Although STAT3 and ... -
Targeting STAT5 in Hematologic Malignancies through Inhibition of the Bromodomain and Extra-Terminal (BET) Bromodomain Protein BRD2
Liu, Suhu; Walker, Sarah Rebecca; Nelson, E; Cerulli, R.; Xiang, Michael; Toniolo, P. A.; Qi, Jun; Stone, Richard Maury; Wadleigh, Martha; Bradner, James Elliott; Frank, David Alan (American Association for Cancer Research (AACR), 2014)The transcription factor signal STAT5 is constitutively activated in a wide range of leukemias and lymphomas, and drives the expression of genes necessary for proliferation, survival, and self-renewal. Thus, targeting STAT5 ... -
Targeting STATs for cancer therapy: “Undruggable” no more
Frank, David A. (Landes Bioscience, 2012)We are in the midst of an exciting transition in the treatment of cancers, from the empirically developed non-specifically cytotoxic drugs to the era of rationally derived molecularly targeted therapies. Over the past 15 ... -
The transcriptional modulator BCL6 as a molecular target for breast cancer therapy
Walker, Sarah R.; Liu, Suhu; Xiang, Michael; Nicolais, Maria; Hatzi, Katerina; Giannopoulou, Eugenia; Elemento, Olivier; Cerchietti, Leandro; Melnick, Ari; Frank, David A. (2014)Inappropriate expression or activation of transcription factors can drive patterns of gene expression leading to the malignant behavior of breast cancer cells. We have found that the transcriptional repressor BCL6 is highly ...