Cell and Developmental Biology Commons^™

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …

Characterization Of A Morphogenetic Furrow Specific Gal4 Driver In The Developing Drosophila Eye, Ankita Sarkar, Neha Gogia, Kevin Farley, Lydia C. Payton, Amit Singh

Biology Faculty Publications

The ability to express a gene of interest in a spatio-temporal manner using Gal4-UAS system has allowed the use of Drosophila model to study various biological phenomenon. During Drosophila eye development, a synchronous wave of differentiation called Morphogenetic furrow (MF) initiates at the posterior margin resulting in differentiation of retinal neurons. This synchronous differentiation is also observed in the differentiating retina of vertebrates. Since MF is highly dynamic, it can serve as an excellent model to study patterning and differentiation. However, there are not any Gal4 drivers available to observe the gain- of- function or loss- of- function of a …

Stimulating Canonical Wnt Signaling In Pituitary Progenitors Inhibits Differentiation Of Hormone Cell Types, Tanner F. Coleman

Senior Theses

The mouse pituitary gland secretes hormones that regulate many physiological processes including growth, stress response, and reproduction. The canonical WNT signaling pathway, activation of which results in nuclear accumulation of β-CATENIN and transcription of target genes including LEF1, is crucial for proper development of the pituitary gland. Pituitary progenitors that lack β-CATENIN at embryonic day of development 8.5 (E8.5) cannot form three of the six cell types of the anterior pituitary that produce growth hormone (GH), thyroid stimulating hormone (TSH), and prolactin (PRL). Additionally, stimulating canonical WNT signaling through creation of degradation-resistant β-CATENIN at E9.5 causes pituitary tumors and results …

Differential Gene Expression In Response To Hypoxia And Acidosis In Chest Wall Deformities And Chondrosarcoma, Jamie L. Durbin

Biological Sciences Theses & Dissertations

The importance of understanding how costal cartilage chondrocytes respond to stimuli such as oxidative stress and low pH has been largely overlooked in studies involving tissue culturing due to major differences between oxygen and pH levels during incubation and the natural environment of hyaline cartilage. Hyaline cartilage is avascular and naturally hypoxic which subsequently leads to increased glycolytic metabolism and ultimately causes a decrease in extracellular pH. To examine how healthy costal cartilage responds to these extreme growth conditions, we examined responses in three hyaline cartilage diseases. Our ability to identify the disease mechanisms responsible for pectus excavatum, pectus carinatum, …

Novel Evidence That Extracellular Nucleotides And Purinergic Signaling Induce Innate Immunity-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells, Mateusz Adamiak, Kamila Bujko, Monika Cymer, Monika Plonka, Talita Glaser, Magda Kucia, Janina Ratajczak, Henning Ulrich, Ahmed Abdel-Latif, Mariusz Z. Ratajczak

Internal Medicine Faculty Publications

Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced “sterile inflammation” in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers. Furthermore, after its release into the extracellular space, ATP is processed by ectonucleotidases: CD39 converts ATP to AMP, and CD73 converts AMP to …

Regulation Of Trophoblast Invasion By Pyruvate Kinase Isozyme M2 (Pkm2), Juan Mejia, Parker Hall, Kelsey Hirschi, Paul R. Reynolds, Juan Arroyo

Student Works

The Pyruvate kinase isozymes M2 (PKM2) protein is a metabolic enzyme that regulates the final step of glycolysis. This enzyme is present in highly proliferating cells such as those present in embryonic tissues, cancer and in the placental trophoblast. We recently studied PKM2 protein in the human placenta at term. Our results demonstrated upregulated placental PKM2 during preeclampsia (PE) where trophoblast invasion is decreased and hypoxia is present. Our objective was to determine the cytosolic and nuclear PKM2 expression pattern and determine PKM2 regulation of trophoblast cell invasion. Trophoblast cells were cultured in normoxic and hypoxic conditions and real time …

Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian Conway, Patrick J. Cullen, James Curtin

Articles

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are signifcantly increased when exposed to 75kV CAP generated by dielectric barrier discharge. No signifcant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological efects of CAP, long-lived reactive species …

Changes In The Proliferation And Gene Expression Of Huvecs In Response To Treatment With Plant Secondary Metabolites, Caleigh Howard

Seaver College Research And Scholarly Achievement Symposium

Medicinal plants have historically been a valuable source of new drugs, and Southern California possesses a rich collection of native plants which have been used as medicines by native people groups for thousands of years. Angiogenesis is the biological process of new blood-vessel growth from endothelial cells. It is an essential part of the wound-healing process, and increased angiogenesis has also been implicated in the growth of some types of cancerous tumors. In this study, extracts of the Southern Californian native plants Red shanks (Adenostoma sparsifolium) and the alkaloid extract of Jimson weed (Datura wrightii) were …

Pre-Diagnostic Biomarkers Of Metabolic Dysregulation And Cancer Mortality, Tomi Akinyemiju, Justin Xavier Moore, Suzanne E. Judd, Maria Pisu, Michael Goodman, Virginia J. Howard, Leann Long, Monika Safford, Susan C. Gilchrist, Mary Cushman

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.

METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), …

Self-Oligomerization Regulates Stability Of Survival Motor Neuron Protein Isoforms By Sequestering An ScfSlmb Degron, Kelsey M. Gray, Kevin A. Kaifer, David Baillat, Ying Wen, Thomas R. Bonacci, Allison D. Ebert, Amanda C. Raimer, Ashlyn M. Spring, Sara Ten Have, Jacqueline J. Glascock, Kushol Gupta, Gregory D. Van Duyne, Michael J. Emanuele, Angus I. Lamond, Eric J. Wagner, Christian L. Lorson, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCF^Slmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCF^Slmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. …

Identification Of Regulatory Mirnas Associated With Ethanol-Induced Microglial Activation Using Integrated Proteomic And Transcriptomic Approaches, Brandi Jo Cook

USF Tampa Graduate Theses and Dissertations

Chronic consumption of, and acute intoxication from, alcohol can have profound effects on the functional integrity of the central nervous system (CNS). The resident immunomodulatory cells of the CNS, microglia, provide signaling factors with both pro- and anti-inflammatory effects for protection. Microglial activation ranges through a multiplex of phases, of which have yet to be defined when induced by exposure to alcohol, and how the activation impacts surrounding cells. Exposure of alcohol has been revealed to induce an immune response in microglia, which can exhibit characteristics unique to a pro-inflammatory response depending on dose and time of alcohol exposure. To …

The Life Of A Microtubule, Ram Dixit, Sabine Petry

Biology Faculty Research

The Minisymposium “The Life of a Microtubule: Birth, Dynamics and Function” highlighted new findings on how microtubules (MTs) are made, how their length and spatial organization is regulated, and finally how they contribute to cellular functions.

Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou

Urology Faculty Publications

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …

5-Lipoxygenase (5-Lox)-5-Lipoxygenase Activating Protein (Flap)-Nanodisc Complex: A Model For The 5-Lox-Flap Interaction, Erin Elizabeth Schexnaydre

LSU Doctoral Dissertations

Leukotrienes (LT) are lipid mediators of the inflammatory response that play important roles in diseases such as asthma and atherosclerosis. Leukotriene A4 (LTA₄) is synthesized from arachidonic acid (AA) by 5-lipoxygenase (5-LOX) with the help of 5-lipoxygenase activating protein (FLAP), a trimeric nuclear transmembrane protein. Exactly how 5-LOX and FLAP interact is not well understood, however FLAP is essential for the production of leukotrienes in vivo. I used nanodiscs (NDs), engineered membrane systems, as a tool to study the 5-LOX-FLAP interaction. FLAP was incorporated into NDs with a phospholipid composition to mimic of the nuclear membrane. Structural features …

Maternal Protein Restriction (Mpr): A Risk Factor For Acute Respiratory Distress Syndrome (Ards), Reza Khazaee

Western Research Forum

Background: Acute respiratory distress syndrome (ARDS) is defined as severe lung dysfunction. The lung impairments in ARDS result from alterations to pulmonary surfactant; a lipid-protein mixture coating the inside of the lung and maintains the lungs’ ability to expand easily. Due to a lack of effective pharmacological therapies mortality associated with ARDS is over 30%. Our research focuses on risk factors that indicate a susceptibility to the disease, which could provide new and early therapeutic options. One such potential risk factor is Maternal Protein Restriction (MPR). MPR is defined by low birth weight and contributes to a variety of adult-onset …

Mitochondrial Transplantation Strategies As Potential Therapeutics For Central Nervous System Trauma, Jenna L. Gollihue, Samir P. Patel, Alexander G. Rabchevsky

Spinal Cord and Brain Injury Research Center Faculty Publications

Mitochondria are essential cellular organelles critical for generating adenosine triphosphate for cellular homeostasis, as well as various mechanisms that can lead to both necrosis and apoptosis. The field of “mitochondrial medicine” is emerging in which injury/disease states are targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. Consequently, novel mitochondrial transplantation strategies represent a potentially multifactorial therapy leading to increased adenosine triphosphate production, decreased oxidative stress, mitochondrial DNA replacement, improved bioenergetics and tissue sparing. Herein, we describe briefly the history of mitochondrial transplantation and the various techniques used for both in …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

Valued readers, it is with a heavy heart that I inform you that this is the last issue of Killi-Data News. The good news is that we will be back as Killifish Research Review. The dissolution of Killi-Data International created a prob- lem: how can the newsletter of a defunct organization live on without that organization? But other additional problems were building in the background. The first issue numbered 15 pages. The previous issue was 28 pages. The number of killifish related papers is increasing while time on our end (the editorial team) is running out. It takes a lot …

Killi-Data News (Fall), Tyrone Genade

Killifish Research Review

Many interesting papers have been published over the last three months. The large volume of papers coupled with the start of the new college semester (and the workload it brings) delayed this issue of Killi-Data News. But better late than never—or so I hope! In this issue Richard van der Laan provides an insightful review of the recent Aphanius papers as to their taxonomic implications and questions. The systematic issues he raises show the importance of the Molecular project: we need to get more samples of the various cyprinodontiforme families to resolve unsettled systematic and taxonomic issues. In the Next …

Killi-Data News (Summer), Tyrone Genade

Killifish Research Review

Over the last three months several interesting and exciting pa- pers have been published. By now most of you have heard the Nothobranchius fish poo news emanating from the Valenzano lab. That paper is reviewed and certainly has repercussions for the health of our captive fish. Polaçik et al have published interesting data with ramifications as to how we breed and incubate annual killifish. The big news in this issue is the paper from the Reznick lab which Jean Huber reviews. The contents of that paper goes to the heart of the question of just what a killifish is. The …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …