Biochemistry, Biophysics, and Structural Biology Commons^™

Biochemical Characterization Of Rna Polymerases Across The Domains Of Life, Stephanie Lois Cooper

All ETDs from UAB

RNA polymerases perform the essential function of RNA synthesis from a DNA template. This process, known as transcription, is critical for all living species and a key point for regulation of gene expression. The function of RNA polymerases allow species from all domains of life to not only survive, but also respond to environmental changes such as heat and nutrient deprivation. In biological taxonomy, the highest classification is domain. The three domains are Eukarya, Bacteria, and Archaea. The domain Eukarya contains all eukaryotic organisms, ranging from yeast, to plants, to metazoans. Bacteria and Archaea are both prokaryotic domains, the species …

Combination Of 64/67cu Theranostics And Immunotherapy Targeting Fibroblast Activation Protein In Triple Negative Breast Cancer, Fnu Sharmila Sridhar

All ETDs from UAB

Triple negative breast cancer (TNBC) makes up 10-20% of breast cancer cases. Even with advancements in science, TNBC is treatment resistant due to the lack of any type of hormonal receptors on the cell surface making it difficult for targeted hormonal therapy. New research avenues have led to studies of the Tumor-microenvironment (TME) in detail. TME is a complex network of stromal cells, extracellular matrix (ECM) and cancer associated fibroblasts (CAFs) with pro-tumorigenic properties and plays a major role in tumor growth. Fibroblast activation protein (FAP) is a marker of CAF and promotes ECM remodeling through several pathways and has …

Uncovering The Contribution Of Desmoplakin Isoforms To Desmosome Structure And Function, Krishna Patel

All ETDs from UAB

UNCOVERING THE CONTRIBUTION OF DESMOPLAKIN ISOFORMS TO DESMOSOME STRUCTURE AND FUNCTION KRISHNA PATEL MULTIDISCIPLINARY BIOMEDICAL SCIENCE ABSTRACT Desmosomes are cell-cell junctions that maintain the integrity of tissues that experience significant mechanical stress, such as the skin and heart. Desmosomal plaque proteins are connected to the intermediate filaments by desmoplakin (DP), and genetic variants in DP are associated with several skin and heart pathologies, including erythrokeratodermia and arrhythmogenic cardiomyopathy. DP contains three domains: an N-terminal plakin head, a central rod, and an intermediate filament-binding C-terminal tail. Furthermore, DP has three splice isoforms (DPI, DPIa, and DPII) that differ only in the …

Elucidating The Nanoscale Architecture Of The Desmosome, William F. Dean

All ETDs from UAB

Desmosomes are intercellular anchoring junctions that are crucial for maintaining the mechanical integrity of tissues routinely subjected to large forces, such as epithelia and cardiac muscle. Adhesion in desmosomes is mediated by a specialized class of transmembrane glycoproteins known as the desmosomal cadherins (DCs). Defects in desmosomal adhesion are associated with severe disease of the heart and skin and are frequently linked to mutations in the DCs. It is therefore important to understand the relationship between DC architecture and desmosome function. Accordingly, several groups have attempted to elucidate DC architecture—primarily using electron tomography (ET). However, ET studies of the desmosome …

Use Of Molecular Dynamics Simulations To Characterize Structural Interactions Of Protein And Drug In Antiviral Drug Discovery, Caitlin Joan Smith

All ETDs from UAB

Since 2019, the novel coronavirus SARS-CoV-2 the etiological cause of the COVID-19 pandemic has led researchers and physicians to look for effective antiviral treatments as interventions in mitigating COVID-19 disease. The severity of the disease and the limitations of current treatments have led to antiviral drug research beyond currently approved antiviral drugs. Many antivirals exist and are currently approved by the Food and Drug Administration (FDA) for other viral illnesses, yet currently only remdesivir and nirmatrelvir/ritonivir are approved for COVID-19 (October 2020, May 2023, respectively), while molnupiravir is still under emergency FDA use authorization [1, 2, 3]. Here, we have …

A Histone Methyltransferase Contributes To Treatment Resistance In Npm1c Aml, Neha Srinivas

All ETDs from UAB

Acute myeloid leukemia (AML) is a blood cancer marked by the rapid growth of abnormal myeloid cells, driven by various genetic mutations. AML accounts for approximately 1% of all cancers and presents complicated prognosis and treatment. Menin inhibitors have shown potential in targeting AML. However, resistance to these inhibitors presents a significant clinical obstacle, as patients treated with menin inhibitors are increasingly developing resistance to the treatment. Using CRISPR-Cas9 mediated screening, we identified an epigenetic regulator contributing to resistance against menin inhibitors in AML. Utilizing knockout (KO) models of the epigenetic regulator in-vitro, ex-vivo, and in-vivo, we observed a growth …

Biologic Evaluation Of 64cu & 67cu As Potential Theranostic Agents For Cancer Radiotherapy, Lakshmi Madhusoodanan

All ETDs from UAB

Immunotherapy has become a mainstay in the treatment of several types of cancer, with the potential to induce durable remission, albeit in a limited percentage of patients. More recently, radiopharmaceuticals have gained recognition in cancer treatment due to their ability to localize within cancer cells and deliver radiation, reducing adverse effects precisely. Cancer radiotherapy has the potential to synergize with immunotherapy due to its induction of immunogenic cell death (ICD), which results in distinct cellular injuries such as the formation of single-strand breaks (SSBs) and double-stranded breaks (DSBs), disruption of mitochondrial integrity, and the excessive generation of reactive oxygen species …

Determination Of Readthrough Susceptibility Among Different Schwann Cell Lines Carrying Nonsense Mutations, Trushali Vansadia

All ETDs from UAB

Neurofibromatosis Type 1 (NF1) is a genetic disorder that affects the nervous system through the formation of tumors or neurofibromas. Encoded by the NF1 gene, neurofibromin functions as a tumor suppressor by converting active GTP-Ras to inactive GDP-Ras. 20% of NF1 patients carry a genomic nonsense mutation, which generates a premature termination codon (PTC) in the NF1 mRNA, leading to the formation of a truncated neurofibromin protein. Termination at PTCs can be suppressed by the incorporation of an amino acid at the site of the PTC, also known as readthrough. Readthrough results in continued translation elongation downstream of the PTC …

Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Subclinical babesiosis observed in captive Eld’s deer, which act as reservoirs for ticks, poses a risk to healthy herds. However, the knowledge of biomarkers for subclinically infected Eld’s deer and host-parasite interactions is limited. This study aimed to investigate the serum proteomic profiles and protein interactions of Babesia bovis and subclinically infected Eld’s deer, PCR-positive for B. bovis, using automated serum protein electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The findings revealed albumin and four globulin fractions: alpha-1, alpha-2, beta, and gamma globulin. Albumin protein (ALB) was consistently detected across all fractions, highlighting its role in maintaining osmotic balance …

Mechanistic Study Of Dna Ligase Iv-Mediated Double-Strand Break Repair In Non-Homologous End Joining, Tasmin Naila, Alan E. Tomkinson

Biomedical Sciences ETDs

Non-homologous end joining (NHEJ) is a crucial double-strand break repair pathway in mammalian cells, resolving DNA damage from ionizing radiation and during V(D)J recombination. Although DNA Ligase IV is the only mammalian DNA ligase involved in NHEJ, it functions as a single-turnover enzyme in vitro. Recent cryo-electron microscopy (cryo-EM) studies revealed two LigIV molecules at the NHEJ synapse, supporting the hypothesis that two ligase molecules are needed for DSB repair by NHEJ. This study aims to validate this hypothesis by providing evidence for coordinated ligation at optimal distance and polarity preference for catalytic activity by LigIV. We determined that coordination …

Regulatory, Structural And Functional Studies Of The Adp-Glucose Pyrophosphorylase From Photosynthetic And Heterotrophic Organisms, Gabriela Martinez-Ramirez

Dissertations

The production of biofuels like ethanol has increased with the transition to renewable energy. Starch can be converted into ethanol through chemical modification. Increasing the availability of starch is crucial to fight back climate change thus, researchers have focused on the biotechnological modification of plants. This modification is known as transgenics, where a plant is modified by the insertion of genes, to make it as productive as possible. The genes inserted code for enzymes that control pathways responsible for the synthesis of certain biomolecules, in this case starch. The synthesis of starch in plants (as glycogen in both photosynthetic and …

Methane Fluxes In Tidal Marshes Of The Conterminous United States, Ariane Arias-Ortiz, Jaxine Wolfe, Scott D. Bridgham, Sara Knox, Gavin Mcnicol, Brian A. Needelman, Julie Shahan, Ellen J. Stuart-Haëntjens, Lisamarie Windham-Myers, Patty Y. Oikawa, Dennis D. Baldocchi, Joshua S. Caplan, Margaret Capooci, Kenneth M. Czapla, R. Kyle Derby, Heida L. Diefenderfer, Inke Forbrich, Gina Groseclose, Jason K. Keller, Cheryl Kelley, Amir E. Keshta, Helena S. Kleiner, Ken W. Krauss, Robert R. Lane, Sarah Mack, Serena Moseman-Valtierra, Thomas J. Mozdzer, Peter Mueller, Scott C. Neubauer, Genevieve Noyce, Katrina V. R. Schäfer, Rebecca Sanders-Demott, Charles A. Schutte, Rodrigo Vargas, Nathaniel B. Weston, Benjamin Wilson, J. Patrick Megonigal, James R. Homquist

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Methane (CH4) is a potent greenhouse gas (GHG) with atmospheric concentrations that have nearly tripled since pre-industrial times. Wetlands account for a large share of global CH4 emissions, yet the magnitude and factors controlling CH4 fluxes in tidal wetlands remain uncertain. We synthesized CH4 flux data from 100 chamber and 9 eddy covariance (EC) sites across tidal marshes in the conterminous United States to assess controlling factors and improve predictions of CH4 emissions. This effort included creating an open-source database of chamber-based GHG fluxes (https://doi.org/10.25573/serc.14227085). Annual fluxes across chamber and EC sites averaged 26 ± 53 g CH4 …

Myc Induces Oncogenic Stress Through Rna Decay And Ribonucleotide Catabolism In Breast Cancer, Jitendra K Meena, Jarey H Wang, Nicholas J Neill, Dianne Keough, Nagireddy Putluri, Panagiotis Katsonis, Amanda M Koire, Hyemin Lee, Elizabeth A Bowling, Siddhartha Tyagi, Mayra Orellana, Rocio Dominguez-Vidaña, Heyuan Li, Kenneth Eagle, Charles Danan, Hsiang-Ching Chung, Andrew D Yang, William Wu, Sarah J Kurley, Brian M Ho, Joseph R Zoeller, Calla M Olson, Kristen L Meerbrey, Olivier Lichtarge, Arun Sreekumar, Clifford C Dacso, Luke W Guddat, Dominik Rejman, Dana Hocková, Zlatko Janeba, Lukas M Simon, Charles Y Lin, Monica C Pillon, Thomas F Westbrook

Faculty, Staff and Students Publications

Upregulation of MYC is a hallmark of cancer, wherein MYC drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels cancer growth and survival, the consequences and metabolic stresses induced by excess cellular RNA are poorly understood. Herein, we discover that RNA degradation and downstream ribonucleotide catabolism is a novel mechanism of MYC-induced cancer cell death. Combining genetics and metabolomics, we find that MYC increases RNA decay through the cytoplasmic exosome, resulting in the accumulation of cytotoxic RNA catabolites and reactive oxygen species. Notably, tumor-derived exosome mutations abrogate MYC-induced cell death, suggesting …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

Predicting The Association Of Metabolites With Both Pathway Categories And Individual Pathways, Erik D. Huckvale, Hunter Moseley

Markey Cancer Center Faculty Publications

Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their …

Michael Mcgraw: Profile Of The Newest Chbc Faculty Member, Danna Jaimes-Fajardo, Jeremy J. Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

Presents the research profile of Michael McGraw, Assistant Professor, Chemistry and Biochemistry department. It highlights his research interests, education, and impact of his research.

Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Chayakrit Krittanawong, Yusuf Kamran Qadeer, Song Peng Ang, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized.

METHODS: This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest.

RESULTS: Our findings showed that the SCAD …

Death-Associated Protein Kinase 3 Modulates Migration And Invasion Of Triple-Negative Breast Cancer Cells, Junkai Wang, Anh M Tran-Huynh, Beom-Jun Kim, Doug W Chan, Matthew V Holt, Diana Fandino, Xin Yu, Xiaoli Qi, Jin Wang, Weijie Zhang, Yi-Hsuan Wu, Meenakshi Anurag, Xiang H F Zhang, Bing Zhang, Chonghui Cheng, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Sixteen patient-derived xenografts (PDXs) were analyzed using a mass spectrometry (MS)-based kinase inhibitor pull-down assay (KIPA), leading to the observation that death-associated protein kinase 3 (DAPK3) is significantly and specifically overexpressed in the triple-negative breast cancer (TNBC) models. Validation studies confirmed enrichment of DAPK3 protein, in both TNBC cell lines and tumors, independent of mRNA levels. Genomic knockout of DAPK3 in TNBC cell lines inhibited in vitro migration and invasion, along with down-regulation of an epithelial–mesenchymal transition (EMT) signature, which was confirmed in vivo. The kinase and leucine-zipper domains within DAPK3 were shown by a mutational analysis to be essential …

A Curious Case Of Medium-Vessel Vasculitis, Nisa N Ilsin, Haleigh D Stafford, Anna Catinis, Theodore Rosen

Faculty, Staff and Students Publications

Vasculitis, or the inflammation of vessels due to primary or secondary causes, may arise from numerous etiologies, often leading to diagnostic uncertainty. Delayed treatment due to diagnostic or etiologic uncertainty presents a significant clinical risk, with consequences including organ failure and mortality. We describe a case of a 58-year-old male with a history including ankylosing spondylitis who presented with painful ulcers involving the bilateral lower extremities following a trip to the southern Texas border. Histopathology revealed medium-vessel vasculitis; however, the search for a likely etiology in the setting of a unique combination of potential vasculitis precipitants, including glochid inoculation, a …

Understanding The Mystery Of R-Loops And Their Relationship To Nucleolar Stress, Kevin Shane

Master's Theses

Genomic instability is an increase in the likelihood of DNA mutations and genetic changes during cell division, a common feature in cancer cells. One cause of genomic instability comes from the aberrant formation of three-stranded nucleic acid structures called R-loops. R-loop form when an RNA strand hybridizes to its complementary strand of DNA, forming a stable RNA:DNA hybrid and displacing one free strand of DNA 1. Accumulation of unscheduled R-loops can lead to replication stress, fork collision, gene expression changes, and double-strand breaks that are underlying causes of genome instability and the development of many diseases, including cancer 2. Many …

Diverse Origins Of Near-Identical Antifreeze Proteins In Unrelated Fish Lineages Provide Insights Into Evolutionary Mechanisms Of New Gene Birth And Protein Sequence Convergence, Nathan Rives, Vinita Lamba, C.H. Christina Cheng, Xuan Zhuang

Biological Sciences Faculty Publications and Presentations

Determining the origins of novel genes and the mechanisms driving the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. Recently evolved fish antifreeze proteins (AFPs) offer a unique opportunity to explore these processes, particularly the near-identical type I AFP (AFPI) found in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages. Through comprehensive comparative analyses of newly sequenced genomes of winter flounder and grubby sculpin, along with available high-quality genomes of cunner and 14 other related species, the study revealed that near-identical …

Noise Leads To The Perceived Increase In Evolutionary Rates Over Short Time Scales, Brian C. O'Meara, Jeremy M. Beaulieu

Biological Sciences Faculty Publications and Presentations

Across a variety of biological datasets, from genomes to conservation to the fossil record, evolutionary rates appear to increase toward the present or over short time scales. This has long been seen as an indication of processes operating differently at different time scales, even potentially as an indicator of a need for new theory connecting macroevolution and microevolution. Here we introduce a set of models that assess the relationship between rate and time and demonstrate that these patterns are statistical artifacts of time-independent errors present across ecological and evolutionary datasets, which produce hyperbolic patterns of rates through time. We show …

Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma

Dissertations, Theses, and Capstone Projects

During an action potential, voltage-gated sodium channels (VGSC) control sodium ion flow into the cytoplasm of cells by using membrane voltage to alter channel conformation. These membrane proteins exhibit three main functional conformations: closed, open, and fast-inactivated, with transitions between these states dependent on membrane voltage and kinetics. The channels open within 1 millisecond and swiftly transition from open to fast-inactivated within 1-2 milliseconds following membrane depolarization. Subsequent membrane repolarization resets the channels to the closed state. Notably, even at mildly depolarized potentials that preclude channel opening, VGSCs can undergo transitions between the closed and inactivated states, known as closed-state …

Newly Synthesized Pyroglutamate Amide And Its Neuroprotective Effect Against Neurotoxicity Induced Cell Death In Alzheimer's Disease, Nourelhouda Joutey Elamrani

Dissertations, Theses, and Capstone Projects

The neurodegenerative disorder is an umbrella term for a range of conditions that affects the neurons in the human brain causing neuronal cell death. The common pathway is the excitotoxicity, a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity leading to the cell death. One of the most common neurodegenerative disorders is Alzheimer’s disease (AD), which represents 60 – 70% of cases and it ranked fourth cause of mortality in the USA. In Alzheimer’s disease, glutamate released from astrocytes and activates extrasynaptic N-methyl-D-aspartate …

Exploiting The Heavy Chain Glycans For The Improvement Of Radioimmunoconjugates, Cindy Rodriguez

Dissertations, Theses, and Capstone Projects

Radiolabeled antibodies have become indispensable tools in nuclear medicine. However, the natural roles of antibodies within the immune system mean that they have several intrinsic limitations as a platform for radiopharmaceuticals. A handful of recent preclinical studies suggest that binding by FcR and particularly FcyRI can affect the pharmacokinetic profiles of 89Zr-labeled radioimmunoconjugates. Fc receptors (FcR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcRs affect the in vivo performance of radiolabeled antibodies. Antibodies …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Development Of Collagen Mimetic Mini-Fibrils With Tunable Collagenase Susceptibility, Jui Chaugule

Dissertations, Theses, and Capstone Projects

Collagen fibrils are the primary molecular scaffold of all connective tissues and provide the essential support for cell migration and differentiation. Collagen fibrils represent one of the most complex molecular hierarchies: three polypeptide chains in Gly-Xaa-Yaa repeating amino acid sequences, first form the rod-shaped collagen triple helix. These triple helices further self-assemble laterally in a specific manner to form fibrils having the characteristic 67 nm axially repeating structure known as the D-period. Enzymatic digestion of collagen fibrils by matrix metalloproteinases (MMPs) is critical for several physiological processes and is of particular consequence during wound healing. Many of the mechanisms of …

The Epigenetic Impact Of Dietary Choline On Growth Outcomes Of Children Exposed To Gestational Diabetes Mellitus, Ismail Kadam

Dissertations, Theses, and Capstone Projects

Maternal insulin resistance and hyperglycemia lead to gestational diabetes mellitus (GDM) which can cause fetal hyperinsulinemia, ultimately leading to excessive fetal growth associated with macrosomia and increased adiposity at birth. Increased placental macronutrient transport and epigenetic changes in growth and metabolic genes affected by GDM contribute to fetal overgrowth and can result in complications such as overweight/obesity, insulin resistance/type 2 diabetes, cardiovascular disease risk factors, as well as cognitive impairment later in life. Choline, an essential nutrient, participates in lipid and energy metabolism by providing methyl groups for DNA methylation and thus may overcome the hypomethylation of growth and metabolic …

Pm2.5 In The Respirable Air A Threat To Heart Health Investigating The Influence On Cardiovascular Performance And Unmasking The Potential Strategies For Cardio Protection, Bhavana Sivakumar

Theses and Dissertations

Air pollution, characterized by the presence of harmful substances in the atmosphere, represents a significant environmental and public health challenge impacting millions worldwide. The World Health Organization (WHO) reports that approximately 90% of the global population resides in regions where air pollution surpasses the recommended thresholds for healthy air quality. Within the realm of air pollution, the composition of particulate matter emerges as a pivotal consideration, particularly regarding PM2.5, comprising minute particles originating from diverse sources such as combustion processes, industrial operations, and natural phenomena like wildfires and dust storms. PM2.5 exhibit a range of chemical and physical attributes contingent …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …