Cell and Developmental Biology Commons^™

Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim

Electronic Thesis and Dissertation Repository

The retinoblastoma protein (RB) is historically known for its function in cell cycle control. However, mice carrying targeted Rb1 mutations have revealed that RB serves various non-cell cycle control roles. Notably, RB acts as a scaffold that recruits chromatin regulatory proteins, condensin II and enhancer of zeste homolog 2 (EZH2). These complexes protect the genome integrity through maintaining proper chromosome condensation, long range contacts, and transcriptionally repressive histone modification. This thesis explores the mechanistic links that regulate such RB-condensin II complex or that are leveraged upon pharmacological inhibition of the RB-EZH2 complex. First, I identified potential phosphorylation sites in the …

Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice

Electronic Thesis and Dissertation Repository

The Hedgehog (Hh) and Wnt protein signaling pathways are essential in the differentiation of neurons and astrocytes. As there are many known and new players involved in regulating these pathways, the role of the regulators Suppressor of Fused (SUFU) and Never in Mitosis Kinase 2 (Nek2) have either not been previously reported or have not been thoroughly explored. To address this shortfall CRISPR gene editing was used to target SUFU and Nek2 in the mouse P19 embryonal carcinoma cell model of neural differentiation. Hh and Wnt signaling were explored in normal P19 neural differentiation, which occurs in the presence of …

Molecular Basis For Integrin Adhesion Receptor Binding To P21-Activated Kinase 4 (Pak4), Byung Hak Ha, Sezin Yigit, Nailini Natarajan, Elizabeth M. Luoma, David A. Calderwood, Titus J. Boggon

SHU Faculty Publications

Integrin adhesion receptors provide links between extracellular ligands and cytoplasmic signaling. Multiple kinases have been found to directly engage with integrin β tails, but the molecular basis for these interactions remain unknown. Here, we assess the interaction between the kinase domain of p21-activated kinase 4 (PAK4) and the cytoplasmic tail of integrin β5. We determine three crystal structures of PAK4-β5 integrin complexes and identify the PAK-binding site. This is a region in the membrane-proximal half of the β5 tail and confirmed by site-directed mutagenesis. The β5 tail engages the kinase substrate-binding groove and positions the non-phosphorylatable integrin residue Glu767 at …

Canalization And Other Design Principles Of Gene Regulatory Networks, Claus Kadelka

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Emerging Role Of Autologous Cd19 Car T-Cell Therapies In The Second-Line Setting For Large B-Cell Lymphoma: A Game Changer?, Razan Mohty, Muhamad A. Moustafa, Mahmoud Aljurf, Hemant Murthy, Mohamed A. Kharfan-Dabaja

Hematology/Oncology and Stem Cell Therapy

Chimeric antigen receptor T-cell (CAR T) therapy has been proven effective in the third-line (and beyond) setting in patients with large B-cell lymphoma (LBCL). Until recently, high-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) was considered the standard of care in the second-line setting in patients demonstrating an objective response before the procedure. The ZUMA-7 and TRANSFORM studies showed the benefit of axicabtagene ciloleucel and lisocabtagene maraleucel, respectively, in patients refractory to or relapsing within 12 months of first-line anthracycline-based chemoimmunotherapy. However, a third trial using tisagenlecleucel failed to show a benefit in the same setting compared to standard …

College Of Natural Sciences Newsletter, September & October 2022, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 3, Issue 6

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 3 Midwest Regional ACS Meeting
Page 4 North Central ASM Meeting
Page 5 Geography Department Travel
Page 6-7 Media Coverage of CNS
Page 7 REMAST Program at SDState receives national spotlight
Page 8 Celebrating the lives of those who touched the College
Page 9 Innovative Learning Spaces
Page 10 Open PRAIRIE Data
Page 11 2022 CNS Scholarship Brunch
Page 12-14 Fall 2022 Outreach Events

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …

Principles Of Aaa+ Proteases, Samar Mahmoud

Doctoral Dissertations

ATPases associated with diverse cellular activities (AAA+) proteases in bacteria help maintain protein homeostasis by degrading misfolded and regulatory proteins. While a handful of protein targets for these proteases have been identified in Caulobacter crescentus and other organisms, more research is needed to elucidate mechanisms that govern substrate specificity. In the second chapter of this thesis, I will elaborate on how AAA+ substrate specificity is less rigid than previous work has suggested and how limiting ATP or mutations can alter substrate preferences of the ClpXP protease. In the third chapter, I will highlight our efforts to use a quantitative proteomics …

Rhamm As A Biomarker And Therapeutic Target In Triple-Negative Breast Cancer, Britney Messam

Electronic Thesis and Dissertation Repository

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterized by early metastases and poor prognosis. Discovering novel biomarkers and therapeutic targets is necessary to improve TNBC patient outcomes as resistance to chemotherapy, the main therapeutic approach for TNBC, is common. In my study, RHAMM promoted proliferation of TNBC MDA-MB-231 tumour cells. RHAMM expression increased sensitivity to doxorubicin (p=0.0002) and strongly increased sensitivity to the FDA-approved MEK1/2 inhibitor trametinib (p≤0.0001). Doxorubicin and trametinib selectively killed RHAMM^+/+ MDA-MB-231 tumour cells grown as co-cultures with RHAMM^-/- MDA-MB-231 tumour cells. RHAMM-loss or trametinib decreased phosphorylated ERK1/2 protein levels and …

Whole Genome Sequencing Of Moraxella Bovis Strains From North America Reveals Two Genotypes With Different Genetic Determinants, Emily L. Wynn, Matthew M. Hille, John Dustin Loy, Gennie Schuller, Kristen L. Kuhn, Aaron M. Dickey, James L. Bono, Michael L. Clawson

Papers in Veterinary and Biomedical Science

Background: Moraxella bovis and Moraxella bovoculi both associate with infectious bovine keratoconjunctivitis (IBK), an economically significant and painful ocular disease that affects cattle worldwide. There are two genotypes of M. bovoculi (genotypes 1 and 2) that differ in their gene content and potential virulence factors, although neither have been experimentally shown to cause IBK. M. bovis is a causative IBK agent, however, not all strains carry a complete assortment of known virulence factors. The goals of this study were to determine the population structure and depth of M. bovis genomic diversity, and to compare core and accessory genes and …

Host-Level Susceptibility And Irf1 Expression Influence The Ability Of Ifn-Γ To Inhibit Kshv Infection In B Lymphocytes, Nedaa Alomari, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, …

Full Issue, Winthrop Mcnair Research Bulletin

The Winthrop McNair Research Bulletin

Winthrop McNair Research Bulletin Volume 5, Full Issue

Locating Mutagen-Sensitivity Gene Mus109 In The Drosophila Melanogaster Genome Using Deficiency Mapping, Chandani Mitchell

The Winthrop McNair Research Bulletin

The complex processes involved in repairing damaged DNA are still being elucidated. Some genes that are known to have roles in the DNA repair process have been identified, such as the mutagen-sensitivity genes, or mus genes, in Drosophila melanogaster. However, the precise genomic location of some mus genes is still unknown, including mus109. It is known that mutations in mus109 cause chromosomal aberrations resulting in larval death, and previous research has mapped mus109 to a region of the X chromosome consisting of over 520,000 nucleotides and 41 genes. Therefore, this study aimed to locate mus109 using deficiency mapping. The mus109D2 …

Activity Of The Lactate Dehydrogenase Inhibitor Oxamic Acid Against The Fermentative Bacterium Streptococcus Mitis/Oralis: Bactericidal Effects And Prevention Of Daptomycin Resistance In Vitro And In An Ex Vivo Model, Razieh Kebriaei, Arnold S. Bayer, Christian K. Lapitan, Michael J. Rybak, Greg A. Somerville, Nagendra N. Mishra

Papers in Veterinary and Biomedical Science

Streptococcus mitis/oralis is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro– derived daptomycin-resistant (DAP-R) S. mitis/oralis strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility. In addition, the strong reliance of S. mitis/oralis on glycolysis for energy and biosynthetic intermediates suggested that inhibiting glycolysis would adversely affect growth and biomass accumulation. To test these hypotheses, we used the lactate dehydrogenase inhibitor …

Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten

PANDION: The Osprey Journal of Research and Ideas

Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …

Art And Illustration Resource For Cell And Molecular Biology: What We Know & How We Found Out, Gerald Bergtrom

Cell and Molecular Biology 5e: What We Know and How We Found Out - All Versions

This Art & Illustration Resource contains the figures (photographs, illustrations etc.) in the 5^th edition Cell and Molecular Biology; What We Know AND How We Found Out (all versions). The images are high-resolution JPG files, sufficient for projection in large size classrooms, and thus useful for creating or supplementing PowerPoint or similar presentations to support classroom, online teaching and learning, and/or to support in-class or homework assignments. Just download and extract the zipped folder to access the chapter-by-chapter numbered figure files. The images are also Open Access (either public domain, CC-licensed, or equivalent). The Chapter-by-Chapter folders come with a …

Glutathione And Glutaredoxin In Redox Regulation And Cell Signaling Of The Lens, Marjorie F. Lou

Papers in Veterinary and Biomedical Science

The ocular lens has a very high content of the antioxidant glutathione (GSH) and the enzymes that can recycle its oxidized form, glutathione disulfide (GSSG), for further use. It can be synthesized in the lens and, in part, transported from the neighboring anterior aqueous humor and posterior vitreous body. GSH is known to protect the thiols of the structural lens crystallin proteins from oxidation by reactive oxygen species (ROS) so the lens can maintain its transparency for proper visual function. Age-related lens opacity or senile cataract is the major visual impairment in the general population, and its cause is closely …

Leaf Phenology And Freeze Tolerance Of The Invasive Tree Pyrus Calleryana (Roseaceae) And Potential Native Competitors, Margaret E. Maloney, Abby Hay, Eric B. Borth, Ryan W. Mcewan

Biology Faculty Publications

Pyrus calleryana is one of the most problematic invasive species in the eastern United States. The mechanisms that enable Py. calleryana to establish and outcompete native plants are not fully understood but likely include a profile of advantageous traits. Extended leaf phenology is a characteristic noted in many woody invasive plants. Leaf phenology of Py. calleryana and two native woody species, Populus deltoides and Platanus occidentalis, was observed in natural areas near Dayton, OH from December 2019 to November 2020. A frost event in May also gave us the serendipitous opportunity to assess frost tolerance of these species. We …

A Review On Serum, Genetic And Mirna Associated Biomarkers For The Early Diagnosis Of Hepatocellular Carcinoma (Hcc)), Ambreen Kanwal, Asima Tayyeb

Journal of Bioresource Management

Hepatocellular carcinoma is the most devastating complication of liver cirrhosis and diagnosis in earlier stages could be useful in curative interventions. The main aim of this review was to analyze current diagnostic biomarkers which are available for the early diagnosis of hepatocellular carcinoma (HCC). For this purpose, we searched different web databases including Medline/Pubmed. We found multiple significant serum biomarkers for imperative diagnosis including α- Fetoprotein, Des- γ -carboxyprothrombin (DCP), Osteopontin (OPN), Glypican-3 (GPC3), Golgi protein-73 (GP73), Squamous cell carcinoma antigen (SCCA), Annexin A2 (ANXA2) and Heat shock protein 70 (HSP70) but all of these represent low sensitivity and low …