Cell and Developmental Biology Commons^™

Investigating Conserved Mechanisms For Embryonic Eye Regrowth In Xenopus Laevis, Cindy Kha

UNLV Theses, Dissertations, Professional Papers, and Capstones

Regeneration is a complex process to replace or restore tissue after damage. However, animals vary in their ability to regenerate tissue, and humans are limited in their abilities. Understanding how regeneration occurs in highly regenerative vertebrates, such as in Xenopus laevis frogs will lead to defining common regeneration mechanisms. In recent years, eye regeneration research in Xenopus laevis tadpoles provided new promising insight into the mechanisms necessary for repair of damaged eye tissue. Much progress has been made towards understanding the regenerative capability of the complex eye since Xenopus tadpoles can regenerate mature eye tissues, including: the optic nerve, retina, …

Screening Tcf19 And Kif18b To Determine Co-Regulation With Mybl1 In Triple Negative Breast Cancer Patient Tissues, Tyra Sharda Ivory

Theses (2016-Present)

The aggressive behavior in triple-negative breast cancer (TNBC) is due to genetic signaling events, which call for the comprehensive analyses of genes differentially regulated in the cancers. Our laboratory previously found that MYBL1 was over-expressed in a fraction of the TNBC, compared to some luminal, and other breast cancer subtypes. The MYBL1 gene is a proto-oncogene that serves as a strong transcriptional activator. The gene is involved in signaling events related to cell cycle signaling, differentiation, proliferation, and apoptosis, all which are differentially regulated in cancers. Because MYBL1 is a transcription regulator, involved in cancer-related mechanisms and differentially expressed in …

The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown

Dartmouth College Ph.D Dissertations

The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …

Novel Functions For Arp2/3 Complex-Mediated Actin Networks Discovered In Chlamydomonas Reinhardtii, Brae M. Bigge

Dartmouth College Ph.D Dissertations

Chlamydomonas reinhardtii, a unicellular member of the Chlorophyta or Green Algae phylum, has been used for decades as a model for ciliary studies. Using this tool, previous work from our lab found a role for actin in ciliary assembly and maintenance. However, while the microtubule-based, membrane-ensheathed cilia of Chlamydomonas are highly conserved in relation to mammalian cells, the actin cytoskeleton is not as simple. Chlamydomonas contains two actin genes: IDA5, a conventional actin, and NAP1, a divergent actin. Here, we find that despite the divergence of NAP1, it is still able to interact with the actin nucleator, the Arp2/3 complex. …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

In Vivo Evaluation Of (-)-Zampanolide Demonstrates Potent And Persistent Antitumor Efficacy When Targeted To The Tumor Site., Leila Takahashi-Ruiz, Joseph D Morris, Phillip Crews, Tyler A Johnson, April L Risinger

Natural Sciences and Mathematics | Faculty Scholarship

Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but …

Renal Cell Carcinoma Of Pelvic Kidney With Atypical Nodal Metastasis: A Diagnostic Challenge, Roshan-E-Shahid Rana, Muhammad Hammad Ather

Section of Urology

Ectopic pelvic kidney is a known congenital anomaly; however, the presence of renal cell carcinoma (RCC) in an ectopic kidney is rare with the evidence available in the form of a few case reports only. In this case report, we present a case of metastatic RCC in the pelvic kidney which became a diagnostic challenge because of atypical contrast-enhanced computed tomographic (CT) characteristics and unusual pattern of lymph node involvement including cervical lymph node in the absence of visceral metastasis. Because of its unusual location and uncertain vascular anatomy, ectopic kidney poses a surgical challenge. Owing to the rarity of …

Genome-Wide Characterization Of Salmonella Typhimurium Genes Required For The Fitness Under Iron Restriction, Sardar Karash, Tieshan Jiang, Young Min Kwon

Poultry Science Faculty Publications and Presentations

Background

Iron is a crucial element for bacterial survival and virulence. During Salmonella infection, the host utilizes a variety of mechanisms to starve the pathogen from iron. However, Salmonella activates distinctive defense mechanisms to acquire iron and survive in iron-restricted host environments. Yet, the comprehensive set of the conditionally essential genes that underpin Salmonella survival under iron-restricted niches has not been fully explored.

Results

Here, we employed transposon sequencing (Tn-seq) method for high-resolution elucidation of the genes in Salmonella Typhimurium (S. Typhimurium) 14028S strain required for the growth under the in vitro conditions with four different levels of iron …

Characterization Of The Responses To Chronic Stress In Caenorhabditis Elegans, Amy Laura Knight

Theses and Dissertations

Exposure to chronic temperature stress influences organismal phenotypes that are important for human health, agriculture, and ecology. In this thesis, the model organism Caenorhabditis elegans was used to study the effects of temperature stress on reproduction and lifespan. It was found that worms demonstrated a rapid shut down in egg-laying between 18-24 hours of exposure to 28°C. Despite this reproductive defect, the overall lifespan of worms was unaffected. At the molecular level, heat shock factor 1 (HSF-1), a regulator of the protective molecular pathway known as the heat shock response (HSR), was identified as important for progeny production during heat …

Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett

USF Tampa Graduate Theses and Dissertations

The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene …

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …

Deciphering Phosphoprotein Phosphatase Signaling Networks Using Proteomics Approaches, Brooke Brauer

Dartmouth College Ph.D Dissertations

Protein phosphorylation is a highly regulated mechanism of cell signaling control and its deregulation is implicated in disease. The kinases that catalyze the addition of phosphate groups onto their substrate proteins have been well studied, their signaling pathways mapped, and their effects on cell and organismal health observed. Knowledge of the phosphatases that reverse the reaction only recently began to come into focus. Phosphoprotein phosphatases (PPPs), long thought to be housekeeping enzymes, are now known to be exquisitely specific towards their substrates, but the exact nature of phosphatase regulation—both upstream and downstream of the phosphatase—is unclear.

PPPs recognize substrates through …

Trends In Utilization Of Human Papillomavirus Vaccines And The Incidence Of Malignant Cervical Cancer In The U.S. Population: A Secondary Analysis, Myah Luna, Soumya Upadhyay

Healthcare Administration and Policy Faculty Research

Background: Human papillomavirus (HPV) is a sexually transmitted infection, and HPV types 16 and 18 are responsible for approximately 66% of all U.S. cervical cancer cases in women. The quadrivalent HPV vaccine was licensed in mid-2006, and it was designed to target and protect against HPV types 6, 11, 16, and 18. The aim of this study is to examine the utilization rate of the HPV vaccine, and the trends and incidence rate of malignant cervical cancer across the United States. Methods: This study utilized data from Surveillance, Epidemiology, and End Results (SEER) and the National Immunization Survey's (NIS) teenage …

The Molecular Mechanism Of Load Adaptation By Branched Actin Networks, Tai-De Li, Peter Bieling, Julian Weichsel, R Dyche Mullins, Daniel A. Fletcher

Advanced Science Research Center

Branched actin networks are self-assembling molecular motors that move biological membranes and drive many important cellular processes, including phagocytosis, endocytosis, and pseudopod protrusion. When confronted with opposing forces, the growth rate of these networks slows and their density increases, but the stoichiometry of key components does not change. The molecular mechanisms governing this force response are not well understood, so we used single-molecule imaging and AFM cantilever deflection to measure how applied forces affect each step in branched actin network assembly. Although load forces are observed to increase the density of growing filaments, we find that they actually decrease the …

Combined Curcumin And Luteolin Synergistically Inhibit Colon Cancer Associated With Notch1 And Tgf-Β Signaling Pathways In Cultured Cells And Xenograft Mice, Rukayat Aromokeye, Hongwei Si

Human Sciences Faculty Research

This study aimed to select a combination of curcumin and luteolin, two phytochemicals from food, at lower concentrations with a higher inhibitory effect on colon cancer growth and investigate possible molecular mechanisms of this anti-colon cancer effect. By pairwise combination screening, we identified that the combination of curcumin (CUR) at 15 μM and luteolin (LUT) at 30 μM (C15L30) synergistically suppressed the proliferation of human colon cancer CL-188 cells, but the individual chemicals had a little inhibitory effect at the selected concentrations. This result was also confirmed in other colon cancer DLD-1cells, suggesting that this synergistic inhibitory effect of C15L30 …

Investigating Roles Of 2 Novel Eklf Targets Involved In Erythropoiesis, Rose M. Gott

ETD Archive

Erythrocytes are primarily comprised of the oxygen carrying protein hemoglobin. Genetic mutations causing defects in the proper synthesis of hemoglobin result in various anemias. It is during the last phases of terminal erythroid differentiation that hemoglobin levels rise, making it a focus for therapeutic research. Fetal hemoglobin is comprised of ⍺-globin and gamma globin, then after a change in gene expression called hemoglobin switching which takes place after birth, adult hemoglobin is comprised of ⍺-globin and beta globin. We investigated hemoglobin switching and erythroid terminal differentiation by focusing on the master erythroid transcription factor Erythroid Krüppel-like Factor (EKLF). Data led …

Bio-Vascular 3d, Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

Cardiovascular disease is a leading cause of mortality and morbidity across the world and according to the world health organization account for 32% of mortality rate globally. There still remain a need to develop better in vitro vascular models that would aid further in-depth understanding of cardiovascular pathogenesis and proposed therapeutic intervention.

This study intends to characterize four novel medically relevant synthetic polymer scaffolds, and one hydrogel, for their biocompatibility and potential application in a tissue engineered blood vessel (TEBV). A primary human endothelial cell line derived from the vein of the umbilical cord (HUVEC), and a human primary smooth …

Short Chain Fatty Acid Combination Treatment Protects Against 6-Ohda Induced Decrease In Neurite Growth In An In Vitro Model Of Parkinson’S Disease., Alex Morris

ORBioM (Open Research BioSciences Meeting)

Title: Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease.

Authors: Alex Morris¹, Louise M. Collins^1,2,3, Gerard W. O’Keeffe², Caitriona M. Guinane¹

¹ Department of Biological Sciences, Munster Technological University (MTU), Cork, Ireland.

² Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.

³ Department of Physiology, University College Cork, Cork, Ireland.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This leads to motor dysfunction which is accompanied by gastrointestinal comorbidities such as constipation …

Complex Role Of Microbiome In Pancreatic Tumorigenesis: Potential Therapeutic Implications, Suneetha Amara, Li V. Yang, Venkataswarup Tiriveedhi, Mahvish Muzaffar

Biology Faculty Research

Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality with limited diagnostic and therapeutic options. Although immunotherapy has shown promise in the treatment of several cancers, its role in pancreatic cancer is rather limited. Several studies have focused on determining the role of the tumor microenvironment with cancer-cell-intrinsic events and tumor-infiltrating immune cellular properties. However, in the past decade, there has been emerging research aimed at delineating the role of the host microbiome, including the metabolites from microbes and host responses, on pancreatic tumorigenesis. Importantly, there is emerging evidence suggesting the beneficial role of a gut microbiome transplant …

Ciliogenesis Mechanisms Mediated By Pak2-Arl13b Signaling In Brain Endothelial Cells Is Responsible For Vascular Stability, Karthikeyan Thirugnanam, Shubhangi Prabhudesai, Emma Van Why, Amy Pan, Ankan Gupta, Koji Foreman, Rahima Zennadi, Kevin R. Rarick, Surya M. Nauli, Sean P. Palacek, Ramani Ramchandran

Pharmacy Faculty Articles and Research

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability. Here, we hypothesized that brain ECs ciliogenesis and the underlying mechanisms that control this process are critical for brain vascular stability. To investigate this hypothesis, we utilized multiple approaches including developmental zebrafish model system and primary cell culture systems. …

Impacts Of Motor Developmental Delay On The Inter-Joint Coordination Using Kinematic Synergies Of Joint Angles During Infant Crawling, Li Zhang, Chun F. Deng, Yuan Liu, Lin Chen, Naong Xiao, Sheng J. Zhai, Wen S. Hou, Yu X. Chen, Xiao Y. Wu

Electrical & Computer Engineering Faculty Research

Motor developmental delay (MDD) usually affects the inter-joint coordination for limb movement. However, the mechanism between the abnormal inter-joint coordination and MDD is still unclear, which poses a challenge for clinical diagnosis and motor rehabilitation of MDD in infant’s early life. This study aimed to explore whether the joint activities of limbs during infant crawling are represented with kinematic synergies of joint angles, and evaluate the impacts of MDD on the inter-joint coordination using those synergies. 20 typically developing infants, 16 infants at risk of developmental delay, 11 infants at high risk of developmental delay and 13 infants with confirmed …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

University Scholar Projects

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

Honors Scholar Theses

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

College Of Natural Sciences Newsletter, May & June 2022, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 3, Issue 4

Page 1 Dean's Message
Page 2 Awards and Recognition
Page 3-4 The path to a Doctorate Degree
Page 4 American Indian Student Center Native Graduate Honoring Ceremony
Page 5 Celebrating the lives of those who touched the College
Page 6 Media coverage of CNS
Page 7 Open PRAIRIE
Page 8-10 CNS Graduation Festivities
Page 11-14 Spring 2022 Dean's List
Page 16 Richard and Janice Vetter Endowed Professorship in Biotechnology.position

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …

The Effects Of Aging On Wound Healing And Limb Regeneration In The Axolotl, Hande Sahin

Graduate Masters Theses

The Mexican axolotl is capable of regenerating various parts of its body and maintains this capacity throughout its entire life. Although this ability is sustained through adulthood, multiple regenerative processes appear to be negatively affected by aging. Here, we focus on evaluating the effect of aging on the rate of wound healing and limb regeneration. We have developed new in vivo, and ex vivo assays to characterize wound healing and identify differences between young and aged animals during this process. We have also characterized morphological features of mature skin from both groups of animals and although there are no obvious …

Low-Salt Diet Reduces Anti-Ctla4 Mediated Systemic Immune-Related Adverse Events While Retaining Therapeutic Efficacy Against Breast Cancer, Durga Khandekar, Debolanle O. Dahunsi, Isaac V. Manzanera Esteve, Sonya Reid, Jeffrey C. Rathmell, Jens M. Titze, Venkataswarup Tiriveedhi

Biology Faculty Research

Immune checkpoint inhibitor (ICI) therapy has revolutionized the breast cancer treatment landscape. However, ICI-induced systemic inflammatory immune-related adverse events (irAE) remain a major clinical challenge. Previous studies in our laboratory and others have demonstrated that a high-salt (HS) diet induces inflammatory activation of CD4+T cells leading to anti-tumor responses. In our current communication, we analyzed the impact of dietary salt modification on therapeutic and systemic outcomes in breast-tumor-bearing mice following anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody (mAb) based ICI therapy. As HS diet and anti-CTLA4 mAb both exert pro-inflammatory activation of CD4+T cells, we hypothesized that a combination of …

Comparative Studies Between The Murine Immortalized Brain Endothelial Cell Line (Bend.3) And Induced Pluripotent Stem Cell-Derived Human Brain Endothelial Cells For Paracellular Transport, Jiahong Sun, Weijun Ou, Derick Han, Annlia Paganini-Hill, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER). Human-induced pluripotent stem cells differentiated into brain microvascular endothelial cells (ihBMECs) have superior barrier properties, but the process of differentiation is time-consuming and can result in mixed endothelial-epithelial gene expression. Here we performed a side-by-side comparison of the …

Noxious Cellular Injury Triggers An Oxidative Stress Gene Response, Shawyun Khoshneviszadeh

Master of Science in Integrative Biology Theses

Wound and regeneration involves a series of complex processes that can induce oxidative stress by elevating intracellular reactive oxygen species (ROS) levels. In this study, we used RNA-seq and qPCR to examine the molecular signature of Human Embryonic Kidney cells (HEK-293T) stimulated with Crotalus atrox (CA) venom. NGS data was assembled and annotated utilizing the Illumina paired-end RNA-seq approach with software packages HISAT2 and StringTie. Results showed 243 genes were differentially expressed (106 upregulated, 137 downregulated) between CA venom stimulated and non-stimulated cells (p<0.05). HEK-293T stimulated with CA venom for 4 hours showed an increase in the expression of oxidative stress response genes (e.g., TOMM6, EGR (1,2,3), HSP70 (1A, 1B), SPRY4, ETV5, and EMP1) (Fold-Change (fc) >2.0). Significantly downregulated genes were associated with many novel transcripts/proteins such as AC117378, AD000671, and AC023509. …