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

Cell Biology Commons

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

Articles 1 - 4 of 4

Full-Text Articles in Cell Biology

Elucidation Of Histone Modifications And Nucleosomal Structure Using Novel Mass Spectrometry Approaches, Kelly Karch Jan 2018

Elucidation Of Histone Modifications And Nucleosomal Structure Using Novel Mass Spectrometry Approaches, Kelly Karch

Publicly Accessible Penn Dissertations

The fundamental repeating unit of chromatin is the nucleosome, composed of 147 base pairs of DNA wrapped around a histone protein octamer containing two copies of H2A, H2B, H3, and H4. Histone proteins are involved in many critical nuclear processes including transcription and maintenance of chromatin structure. Histone function is mediated by a dynamic and extensive array of post-translational modifications (PTMs). Mass spectrometry (MS) has emerged as a leading tool to study these complex histone PTM profiles. Generally, MS experiments utilize data dependent acquisition (DDA) methods on high-resolution MS instruments because they can more readily distinguish PTMs with small mass ...


Tumor Interferon Signaling Initiates And Sustains A Multigenic Resistance Program To Immune Checkpoint Blockade, Joseph Lawrence Benci Jan 2017

Tumor Interferon Signaling Initiates And Sustains A Multigenic Resistance Program To Immune Checkpoint Blockade, Joseph Lawrence Benci

Publicly Accessible Penn Dissertations

Therapeutic blockade of the CTLA4 and/or PD1 immune checkpoint pathways has resulted in significant anti-tumor responses in broad variety of cancer types, but resistance is common. Using mouse models of metastatic melanoma and breast cancer in combination with CRISPR/Cas9 to selectively delete genes in our tumor cells, we demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB), and to combinations such as radiation plus anti-CTLA4. Furthermore, we show that this interferon driven resistance mechanism primarily occurs in ICB resistant tumors and not in ICB responsive tumors. Persistent type II interferon signaling allows ...


Single Human Cells Use Transcriptional Mechanisms To Compensate For Differences In Cell Size And Dna Content, Olivia Padovan-Merhar Jan 2015

Single Human Cells Use Transcriptional Mechanisms To Compensate For Differences In Cell Size And Dna Content, Olivia Padovan-Merhar

Publicly Accessible Penn Dissertations

Human cells are dynamic: they grow, replicate their genetic information (DNA), and divide. Clonal populations of cells can display marked heterogeneity in size, leading to significant variability in the ratio of DNA to cellular volume. Despite this variability, cells must maintain a constant concentration of RNA and protein, produced from DNA, to ensure proper functionality. How do larger cells produce more output from the same amount of DNA? How do cells that have replicated their DNA prior to cellular division produce the same output as before? Using RNA fluorescence in situ hybridization (RNA FISH), we visualize and count individual RNA ...


The Design, Synthesis, And Biological Evaluation Of Steroid-Derived Inhibitors Of The Sonic Hedgehog Signaling Pathway, Lyndsay Michelle Leal Jan 2015

The Design, Synthesis, And Biological Evaluation Of Steroid-Derived Inhibitors Of The Sonic Hedgehog Signaling Pathway, Lyndsay Michelle Leal

Publicly Accessible Penn Dissertations

The Sonic Hedgehog (SHH) signaling pathway is required during embryogenesis for cell differentiation and growth; however, medulloblastoma, a pediatric malignancy in the cerebellum, as well as glioblastoma multiforme (GBM), a malignant and invasive adult brain tumor, also require SHH signaling for growth. As SHH signaling remains inactive in healthy adult cells, this pathway provides an excellent target for chemotherapeutics. Cyclopamine, a naturally occurring alkaloid, inhibits the SHH pathway at the level of Smoothened (SMO) and has demonstrated reduced tumor growth in vivo. However, this alkaloid is metabolically unstable. Analysis of the hydrophobic core of cyclopamine revealed a similarity to the ...