Reena Shakya

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Axin is a component of the canonical Wnt pathway that negatively regulates signal transduction by promoting degradation of beta-catenin. To study the role of Axin in development, we developed strains of transgenic mice in which its expression can be manipulated by the administration of doxycycline (Dox). Animals carrying both mouse mammary tumor virus(More)
Germline mutations of the breast cancer 1 (BRCA1) gene are a major cause of familial breast and ovarian cancer. The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression. To test this hypothesis, we generated mice that express an enzymatically defective Brca1. We found that this(More)
Preclinical studies have suggested that the pancreatic tumor microenvironment both inhibits and promotes tumor development and growth. Here we establish the role of stromal fibroblasts during acinar-to-ductal metaplasia (ADM), an initiating event in pancreatic cancer formation. The transcription factor V-Ets avian erythroblastosis virus E26 oncogene homolog(More)
Many DNA repair factors act to suppress tumor formation by preserving genomic stability. Similarly, the CtIP protein, which interacts with the BRCA1 tumor suppressor, is also thought to have tumor suppression activity. Through its role in DNA end resection, CtIP facilitates DNA double-strand break (DSB) repair by homologous recombination (DSBR-HR) and(More)
Checkpoint inhibition has gained traction as an immu-notherapeutic approach. However, limited efficacy has been observed in patients with pancreatic ductal adenocar-cinoma (PDAC). Prior studies by our group have indicated that human pancreatic stellate cells (PSC), a major component of the pancreatic stroma secrete copious amounts of IL-6, which can act(More)
Exportin-1 (XPO1) is a nuclear export protein with >220 cargo proteins, including tumor suppressors and cell cycle modulators. Selinexor is a SINE (Selective Inhibitor of Nuclear Export) compound that has been administered to >900 cancer patients in Phase I and II trials to date, with evidence of efficacy and tolerability. Selinexor blocks nuclear export of(More)
Pancreatic cancer (PCa) is resistant to cytotoxic therapies, and the profound immune suppressive nature of this disease renders patients non-responsive to immunologic therapies. Signaling downstream of IL-6 is important in the genesis and progression of PCa. The IL-6/Jak2/STAT3 axis also mediates expansion of myeloid-derived suppressor cells (MDSC). Indeed,(More)
Pancreatic ductal adenocarcinoma (PDA) has a prominent stroma which includes collagen, lymphoid, myeloid, and stellate cells. Adequate preclinical models are needed to advance immunotherapy for PDA. Indeed many xenograft models poorly mimic the morphology, stroma, and phenotype of the human PDA microenvironment. Thus, further development and use of relevant(More)
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