Cell Biology Commons^™

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 …

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, …

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 …

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. …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …

Wild-Type P53 Enhances Endothelial Barrier Function By Mediating Rac1 Signalling And Rhoa Inhibition, Nektarios Barabutis, Christiana Dimitropoulou, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Inflammation is the major cause of endothelial barrier hyper-permeability, associated with acute lung injury and acute respiratory distress syndrome. This study reports that p53 "orchestrates" the defence of vascular endothelium against LPS, by mediating the opposing actions of Rac1 and RhoA in pulmonary tissues. Human lung microvascular endothelial cells treated with HSP90 inhibitors activated both Rac1- and P21-activated kinase, which is an essential element of vascular barrier function. 17AAG increased the phosphorylation of both LIMK and cofilin, in contrast to LPS which counteracted those effects. Mouse lung microvascular endothelial cells exposed to LPS exhibited decreased expression of phospho-cofilin. 17AAG treatment …

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Jak/Stat Signaling Regulates Gametogenesis And Age-Related Reproductive Maintenance, Michelle Suzanne Giedt

Theses and Dissertations--Biology

Cell signaling is central to integration of internal and external cues that regulate development and homeostasis. Most development is thought of as pre-adult, but limited developmental processes occur in adults. Gametogenesis incorporates elements of both these facets, with a distinct developmental plan for gamete synthesis which is regulated by integration of homeostatic inputs such as nutrient status, and environmental cues. Signaling pathways integrate and transduce information from these cues to evoke a response. A decline in homeostasis and subsequent cues occurs over time, in the case of reproductive tissues leading to a progressive loss of fertility. The Janus Kinase and …

Association Of Vitamin D Deficiency And Vdbp Gene Polymorphism With The Risk Of Ami In A Pakistani Population, Mujtaba Mubashir, Shaheena Anwar, Asal Khan Tareen, Naseema Mehboobali, Khalida Iqbal, Mohammad Iqbal

Department of Biological & Biomedical Sciences

OBJECTIVE: To investigate the relationship of vitamin D deficiency and risk of AMI in a Pakistani population, and to find out any associationbetween vitamin D binding protein (VDBP) genotypes and risk of AMI in this population.
METHODS: In a comparative cross-sectional study, 246 patients (age: 20-70 years; 171 males and 75 females) with first AMI were enrolled with informed consent. Similarly, 345 healthy adults (230 males and 115 females) were enrolled as controls. Their fasting serum samples were analyzed for 25 (OH) vitamin D, lipids and other biomarkers using kit methods, while DNA was analyzed for VDBP genotypes using PCR-RFLP …

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …

Optimizing A Method For Simultaneous Recovery Of Proteins And Dna From Fingerprints, Steven Kranes

Student Theses

DNA testing on touched objects is a valuable tool in forensic investigations, but DNA is usually present in low amounts, causing poor STR typing results. For touch DNA evidence, there is a clear need for additional individualization, especially for highly probative samples. This could be achieved by testing genetically variable proteins. The goal of this project was to develop a DNA/protein co-extraction method to facilitate DNA and protein testing on the same evidence item. Existing DNA extraction methods were carefully adjusted to allow for downstream mass spectrometry analysis. Initial experiments on saliva and fingerprints placed on glass suggested that trypsin …

The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano

Dissertations, Theses, and Capstone Projects

Autophagy and endocytosis are two cellular pathways that are vital to cell growth and homeostasis. Autophagy is a dynamic and catabolic process involving the formation of a double-membrane vesicle called the autophagosome, which engulfs long-lived proteins and damaged organelles. Endocytosis involves the uptake of extracellular material into the cell through the formation of intracellular vesicles termed endosomes. Although both endocytosis and autophagy are interconnected processes, the extent to which endocytic proteins and/or compartments contribute to autophagy, and how these endocytic components do so, is still unknown. To improve our understanding of the connections that exist between autophagy and endocytosis, we …

The 'Pseudomonas Aeruginosa' Psl Polysaccharide Is A Social But Noncheatable Trait In Biofilms, Yasuhiko Irie, Aled E. Roberts, Kasper N. Kragh, Vernita D. Gordon, Jaime B. Hutchison, Rosalind J. Allen, Gavin Melaugh, Thomas Bjarnsholt, Stuart A. West, Stephen P. Diggle

Biology Faculty Publications

Extracellular polysaccharides are compounds secreted by microorganisms into the surrounding environment, and they are important for surface attachment and maintaining structural integrity within biofilms. The social nature of many extracellular polysaccharides remains unclear, and it has been suggested that they could function as either cooperative public goods or as traits that provide a competitive advantage. Here, we empirically tested the cooperative nature of the PSL polysaccharide, which is crucial for the formation of biofilms in Pseudomonas aeruginosa. We show that (i) PSL is not metabolically costly to produce; (ii) PSL provides populationlevel benefits in biofilms, for both growth and antibiotic …

Characterization Of Neuronal Specific Responses To Induced Misfolded Protein Stress In Caenorhabditis Elegans, Claire Gormley

Senior Honors Projects, 2010-2019

Abstract

Misfolded protein stress has been associated with many types of disease,

including neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s

disease. When a cell accumulates misfolded proteins in the endoplasmic reticulum,

misfolded protein stress occurs and the unfolded protein response (UPR) is triggered to

induce mechanisms that will allow the cell to either survive or undergo cell death. The

nascent polypeptide associated complex (NAC) is a co-translational chaperone and α/β

heterodimer that manages protein folding and localization, and protects against misfolded

protein stress; changes in NAC function have been linked to both neurodegeneration and

cancer. In these studies, I depleted …

Whole Transcriptome Comparison Between Multipotent Adult Stem Cells (Mascs) And Two Families Of Mesenchymal Stem Cells (Mscs), Jessica C. Black, Drew Cumming, Andra Sullivan, Wei-Hua Huang, Paul A. Lucas

NYMC Faculty Posters

No abstract provided.

Sumo Regulates The Activity Of Smoothened And Costal-2 In Drosophila Hedgehog Signaling, Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 …

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …

Genetic Analysis Of Serf Gene Function In Drosophila Melanogaster And Its Contribution To A Fly Model Of Spinal Muscular Atrophy, Swagata Ghosh

Theses and Dissertations--Biology

The Serf gene is evolutionarily highly conserved but its biological function is not known in any organism. In human, SERF1/H4F5 was first identified as a modifier of the disease Spinal Muscular Atrophy (SMA). SMA is caused by mutations in the Survival Motor Neuron 1(SMN1) gene leading to diminished levels of the Smn protein. More than 90% of patients with the most severe form of SMA have deletions that remove SERF1 as well as mutaions within SMN1. Hence, loss of Serf activity is hypothesized to exacerbate SMA disease progression. The primary motivation of this thesis was to test …

An Undergraduate Cell Biology Lab: Western Blotting To Detect Proteins From Drosophila Eye, Neha Gogia, Ankita Sarkar, Amit Singh

Biology Faculty Publications

We have developed an undergraduate laboratory to allow detection and localization of proteins in the compound eye of Drosophila melanogaster, a.k.a fruit fly. This lab was a part of the undergraduate curriculum of the cell biology laboratory course aimed to demonstrate the use of Western Blotting technique to study protein localization in the adult eye of Drosophila. Western blotting, a two-day laboratory exercise, can be used to detect the presence of proteins of interests from total protein isolated from a tissue. The first day involves isolation of proteins from the tissue and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide) gel …

Real-Time Quantitative Pcr To Demonstrate Gene Expression In An Undergraduate Lab, Abijeet Singh Mehta, Amit Singh

Biology Faculty Publications

The objective of this teaching note is to develop a laboratory exercise, which allows students to get a hands-on experience of a molecular biology technique to analyze gene expression. The short duration of the biology laboratory for an undergraduate curriculum is the biggest challenge with the development of new labs. An important part of cell biology or molecular biology undergraduate curriculum is to study gene expression. There are many labs to study gene expression in qualitative manner. The commonly used reporter gene expression studies are primarily qualitative. However, there is no hands-on experience exercise to quantitatively determine gene expression. Therefore, …

The Role Of The Dosage Compensation Complex As A Pathway For Spiroplasma To Induce Male Lethality In Drosophila Melanogaster, Becky Cheng

CMC Senior Theses

Drosophila melanogaster and many other insects harbor intracellular bacterial symbionts that are transmitted vertically from infected host mothers to their offspring. Many of these bacteria alter host reproductive developmental processes in order to increase their transmission success. For example, Spiroplasma, a spirochete that naturally infects D. melanogaster, selectively kills males during mid-embryogenesis while sparing females. Previous studies suggested that Spiroplasma interacts genetically with the male-specific dosage compensation pathway, which causes ~2-fold up-regulation of most genes located on the male’s single X chromosome so that their expression matches the levels found in females who have two Xs. To further …

Cullin-4 Regulates Wingless And Jnk Signaling-Mediated Cell Death In The Drosophila Eye., Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood. In a gain-of-function screen, we found that misexpression of cullin-4 (cul-4), an ubiquitin ligase, can rescue reduced eye mutant phenotypes. Previously, …

Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

The Clinical, Biochemical And Genetic Features Associated With Rmnd1-Related Mitochondrial Disease., Yi Shiau Ng, Charlotte L Alston, Daria Diodato, Andrew A Morris, Nicole Ulrick, Stanislav Kmoch, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, …

Selfish Mutations: The Genetic Basis Of The Paternal Age Effect, Eoin C. Whelan

Biological Sciences Theses & Dissertations

As the mean age of childrearing grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father but have a deleterious effect in offspring.

I present a mathematical model to analyse the normal function of the stem cell compartment, which provides a framework for SSC renewal and accommodates differences between animal systems. In order to model the SSC mutation accumulation, a Markov chain …

Loss Of Cell Adhesion Increases Tumorigenic Potential Of Polarity Deficient Scribble Mutant Cells, Indrayani Waghmare, Madhuri Kango-Singh

Biology Faculty Publications

Epithelial polarity genes are important for maintaining tissue architecture, and regulating growth. The Drosophila neoplastic tumor suppressor gene scribble (scrib) belongs to the basolateral polarity complex. Loss of scrib results in disruption of its growth regulatory functions, and downregulation or mislocalization of Scrib is correlated to tumor growth. Somatic scribble mutant cells (scrib-) surrounded by wild-type cells undergo apoptosis, which can be prevented by introduction of secondary mutations that provide a growth advantage. Using genetic tools in Drosophila, we analyzed the phenotypic effects of loss of scrib in different growth promoting backgrounds. We investigated if a central …

Genetic Analysis Reveals A Hierarchy Of Interactions Between Polycystin-Encoding Genes And Genes Controlling Cilia Function During Left-Right Determination, Daniel T. Grimes, Jennifer L. Keynton, Maria T. Buenavista, Xingjian Jin, Saloni H. Patel, Shinohara Kyosuke, Jennifer Vibert, Debbie J. Williams, Hiroshi Hamada, Rohana Hussain, Surya M. Nauli, Dominic P. Norris

Pharmacy Faculty Articles and Research

During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca²⁺ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we …

Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla

Theses & Dissertations

Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in the Western hemisphere. Despite considerable progress in our current understanding of CLL, this disease remains incurable and the molecular events underlying the complex pathogenesis of CLL are not fully elucidated. Interferon Regulatory Factor 4 (IRF4) belongs to the IRF superfamily of transcription factors that has been shown to play critical roles at multiple stages of B cell development. Interestingly, a Genome Wide Association Study identified Single Nucleotide Polymorphism (SNP) mediated IRF4 down regulation, as a major predisposing genetic event during the development of CLL. However, whether low levels of …