Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 4 of 4

Full-Text Articles in Molecular Biology

Modulation Of Antitumor Immunity By The Mek Inhibitor Trametinib: Implications For Targeted Therapy Of Cancer, Michael J. Allegrezza Jan 2016

Modulation Of Antitumor Immunity By The Mek Inhibitor Trametinib: Implications For Targeted Therapy Of Cancer, Michael J. Allegrezza

Publicly Accessible Penn Dissertations

Through rational drug design, much progress has been made to develop small molecules that specifically inhibit the oncogenic signaling pathways driving malignant growth. However, the normal function of immune cells depends upon many of the same pathways inhibited by such targeted cancer therapies. Because the immune system can influence the growth of many cancers, I hypothesized that most small molecule inhibitors would have activity on leukocytes relevant in cancer, and this activity would contribute to their antitumor mechanisms. In order to test this hypothesis, I first screened a panel of over 40 small molecule inhibitors for their activity on proliferating ...


Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar Jan 2016

Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar

Publicly Accessible Penn Dissertations

With breakthroughs in synthetic biology, improved cell culture techniques and advanced genetic engineering, it has now become possible to generate bi-specific primary human T cells with desired specificities. One mode of redirecting specificity is the modification of T cells to express chimeric antigen receptors (CARs). Recent studies indicate that natural T cells have distinct biochemical and metabolic features that endow them with short lived effector or long lived memory fates. The central objective of this thesis was to investigate whether the signaling endodomain of CARs could reprogram T cells with pre-specified effector and memory fates. This thesis describes a novel ...


Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis, Nicole Aiello Jan 2016

Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis, Nicole Aiello

Publicly Accessible Penn Dissertations

The primary cause of cancer-related deaths is metastasis— the spread of cancer cells to distant organs— and yet the mechanisms underlying this process remain elusive due to the difficulty in detecting early metastatic events, which are rare, stochastic and microscopic. To investigate the cellular and molecular mechanisms of metastasis, I utilized an autochthonous mouse model of pancreatic cancer (KPCY) in which all tumor cells are genetically labeled with yellow fluorescent protein (YFP). The YFP lineage label allows for the detection and isolation of disseminated tumor cells as they delaminate from epithelial structures within the primary tumor, invade into the stroma ...


Defining Mechanisms Of Autoimmunity In Pemphigus Vulgaris, Michael Jeffrey Tejada Cho Jan 2016

Defining Mechanisms Of Autoimmunity In Pemphigus Vulgaris, Michael Jeffrey Tejada Cho

Publicly Accessible Penn Dissertations

A prominent question in the field of autoimmunity is how these diseases arise. Currently, the etiologies of many autoimmune diseases remain unclear. The work described here provides insight into this question in the context of pemphigus vulgaris (PV), a prototypic autoimmune disease characterized by serum autoantibodies to desmoglein (Dsg) 3. We utilize a combination of both antibody phage display and heterohybridoma to probe the anti-Dsg3 antibody repertoires of patients with PV. We first address whether a cohort of four patients with active disease demonstrate any shared characteristics in their anti-Dsg3 antibody repertoires (Chapter 2), and if so, why. We find ...