Cell and Developmental Biology Commons^™

Novel Species-Specific Glycoprotein On The Surface Of Mytilus Edulis And M. Trossulus Eggs, Fiona M. Harper, Kasandra J. Riley, R. D. Rawson

Faculty Publications

Protein–protein interactions play a central role in the gamete attraction, binding, and fusion stages of gamete interactions and fertilization for broadcast spawning species, such as marine mussels in the Mytilus edulis species complex. Although assortative gamete interaction has been implicated in the level of reproductive isolation among the three species in this complex, the molecular basis of these interactions has not been elucidated. Using mass spectrometry peptide sequencing, cDNA sequencing, and bioinformatics approaches, we have investigated species-level variation in the proteins expressed on the surface of mussel eggs. We herein describe an extracellular protein, MESP-1, from the surface of the …

Traceable Peo-Poly(Ester) Micelles For Breast Cancer Targeting: The Effect Of Core Structure And Targeting Peptide On Micellar Tumor Accumulation, Shyam M. Garg, Igor M. Paiva, Mohammad R. Vakili, Rania Soudy, Kate Agopsowicz, Amir H. Soleimani, Mary Hitt, Kamaljit Kaur, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Traceable poly(ethylene oxide)-poly(ester) micelles were developed through chemical conjugation of a near-infrared (NIR) dye to the poly(ester) end by click chemistry. This strategy was tried for micelles with poly(ε-caprolactone) (PCL) or poly(α-benzyl carboxylate-ε-caprolactone) (PBCL) cores. The surface of both micelles was also modified with the breast cancer targeting peptide, P18-4. The results showed the positive contribution of PBCL over PCL core on micellar thermodynamic and kinetic stability as well as accumulation in primary orthotopic MDA-MB-231 tumors within 4–96 h following intravenous administration in mice. This was in contrast to in vitro studies where better uptake of PEO-PCL versus PEO-PBCL micelles …

Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP with …

Tumor Formation In Response To Loss Of Chromatin Remodeler Chd5 In Zebrafish, Taylor R. Sabato, Erin L. Sorlien, Dr. Joseph P. Ogas

The Summer Undergraduate Research Fellowship (SURF) Symposium

Chromodomain helicase DNA binding protein 5 (CHD5) has been identified as a tumor suppressor in humans. Deletion or mutation of CHD5 has been observed in numerous cancers, including neuroblastoma and melanoma. We hypothesize that chd5 is also a tumor suppressor in zebrafish, a powerful model system to study tumorigenesis. Many genes involved in tumorigenesis are conserved in zebrafish, and they develop fully penetrant tumor phenotypes. We have created chd5 knock-out zebrafish using CRISPR/Cas9 and are monitoring them for tumor development. In addition to the chd5 knock-outs, we are undertaking a double-mutant approach by coupling loss …

Relative Contribution Of Porcine Reproductive And Respiratory Syndrome Virus Open Reading Frames 2–4 To The Induction Of Protective Immunity, Katherine Kimpston-Burkgren, Ignacio Correas, Fernando A. Osorio, David Steffen, Asit K. Pattnaik, Ying Fang, Hiep L. X. Vu

Nebraska Center for Virology: Faculty Publications

The minor glycoproteins (GPs) of PRRSV, GP2, GP3, and GP4, form a heterotrimer that is required for viral infectivity, presumably due to its interaction with the key cellular receptor CD163. These 3 GPs are encoded by open reading frames (ORFs) 2a, 3, and 4 (herein referred to as ORFs 2–4), respectively. The goal of this study was to investigate the immunogenicity of the PRRSV-2 minor GPs. Through the use of reverse genetics, a chimeric virus (designated SDFL24) was constructed by replacing ORFs 2–4 of the PRRSV-1 strain SD01-08 with the corresponding genes of the PRRSV-2 strain FL12. While the parental …

Modulation Of Cellular Energetics By Galactose And Pioglitazone., David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E. Konkle, Nilay Chakraborty, Michael A. Menze

Faculty and Staff Scholarship

The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences that are in addition to sensitizing the cells to mitochondrial toxins may occur. As such, the screening of pharmaceutical agents against transformed cells while using galactose must be carefully evaluated. Pioglitazone is used in clinical applications to treat type-2 diabetes, but clearly has other off target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactosecontaining medium to investigate the role of pioglitazone on cellular bioenergetics employing calorimetry and respirometry. Compared to cells …

The Cul3 Ubiquitin Ligase: An Essential Regulator Of Diverse Cellular Processes, Brittney Marie Davidge

Dissertations and Theses

Cul3 forms E3 ubiquitin ligase complexes that regulate a variety of cellular processes. This dissertation describes Cul3's role in several of these pathways and provides new mechanistic details regarding the role of Cul3 in eukaryotic cells. Cyclin E is an example of a protein that is regulated in a Cul3-dependent manner. Cyclin E is a cell cycle regulator that controls the beginning of DNA replication in mammalian cells. Increased levels of cyclin E are found in some cancers, in addition, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with tumorigenesis. Cyclin E levels are …

Increased Expression Of The Tight Junction Protein Tjp1/Zo-1 Is Associated With Upregulation Of Taz-Tead Activity And An Adult Tissue Stem Cell Signature In Carfilzomib-Resistant Multiple Myeloma Cells And High-Risk Multiple Myeloma Patients, Irene Riz, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomiband carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfzlike phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature. siRNA-mediated knockdown of TJP1 or TAZ/TEAD1 partially sensitized LP-1/Cfz cells to carfilzomib. …

Acute Myeloid Leukemia, Adrianna Wayble

Nursing Student Class Projects (Formerly MSN)

The purpose of this research project is to explore the disease process of Acute Myeloid Leukemia, or AML. AML is a disease that is estimated to affect 21,380 people in the U.S., killing 10,590 this year alone according to the National Institute of Cancer (NIC, 2017). The goal of treatment for AML is complete remission, using either a combination of chemotherapy, and/or radiation, followed by stem cell transplant (Wang & Bailey, 2016). The disease is multi-faceted with many factors believed to contribute to AML, from environmental exposures to genetics (Wang & Bailey, 2016). This project discusses the treatment choices for …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same …

A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA …

Ion Channel Signaling Influences Cellular Proliferation And Phagocyte Activity During Axolotl Tail Regeneration, Brandon M. Franklin, S. Randal Voss, Jeffrey L. Osborn

Biology Faculty Publications

Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K_V2.1, K_V2.2, L-type CaV channels and H/K ATPases) or completely (GlyR, GABA_AR, K_V1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in …

Blocking An N-Terminal Acetylation-Dependent Protein Interaction Inhibits An E3 Ligase, Daniel C. Scott, Jared T. Hammill, Jaeki Min, David Y. Rhee, Michele Connelly, Vladislav O. Sviderskiy, Deepak Bhasin, Yizhe Chen, Su-Sien Ong, Sergio C. Chai, Asli N. Goktug, Guochang Huang, Julie K. Monda, Jonathan Low, Ho Shin Kim, Joao A. Paulo, Joe R. Cannon, Anang A. Shelat, Taosheng Chen, Ian R. Kelsall, Arno F. Alpi, Vishwajeeth Pagala, Xusheng Wang, Junmin Peng, Bhuvanesh Singh, J. Wade Harper, Brenda A. Schulman, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are …

Characterizing The Influence Of Gap Junction Communication On Cell Volume Dynamics, Bona Mu

Biology Theses

Cell volume changes are associated with both normal and disease processes, and can serve as a signal for altering cell activities. Most cell types in a multicellular organism express gap junction channels that allow for the direct transfer of ions, metabolites, and other small molecules between neighboring cells. Little is known about the potential role of gap junctions in modulating cell volume dynamics. The present study characterizes what happens to the swelling rates of fast swelling and slow swelling cells when they are coupled together by gap junctions. The initial hypothesis was that water transport through gap junctions from a …

Linear Dna-Linked Nanoparticle Building Blocks (Nblocks) For Modular Self-Assembly Of Nanostructures, Jakob Thomas Hockman

Graduate Theses and Dissertations

Controlling the shapes and sizes of nanomaterials often enables controlling their properties for certain applications. The most promising methods for controlling the shapes and sizes of nanostructures use base-pairing between complementary DNA strands to self-assemble nanostructures from DNA and nanoparticles. DNA Brick-based self-assembly is a particularly useful method for creating DNA nanostructures. It offers a large amount of control over the final shapes and sizes because it uses building blocks that are anisotropic and have predictable geometry. However, this control has not been extended to the self-assembly of nanostructures from nanoparticles. Applying DNA Brick based self-assembly to the self-assembly of …

Examining The Role Of Hres On The Regulation Of Opioid Receptor Gene Expression In Neuronal Cells Undergoing Hypoxic Mimic Condition, Alberto Herrera

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a condition of inadequate oxygen supply, which can induce cell death. Using human neuronal cells treated with a hypoxia memetic compound, desferoxamine (DFO), a hypoxic cell model system was created. Our lab reported previously that treatment with DFO resulted in the decrease of cell viability. However, there were still surviving neurons. The surviving cells did not exhibit significant morphological changes, as compared to the control cells, under confocal microscopy analysis using annexin-V-FLUOS and propidium iodide staining, indicating that they were not at apoptotic or necrotic stages. These surviving neurons, therefore, developed adaptive responses under hypoxic challenge. Several changes …

Defining The Immune Response And Cellular Pathologies In Multiple System Atrophy, Annamarie Valenti

Masters Theses

Multiple System Atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded α-synuclein (α-Syn) in oligodendrocytes of the central nervous system (CNS). A previous study in our lab used Affymetrix DNA microarray analysis to show the downregulation of various mitochondrial related genes, as well as the upregulation of genes involved in inflammatory/immune responses in MSA brain tissue. Therefore, it is hypothesized that an increased presence of immune proteins exists in the MSA brain accompanied by glial cell pathology including decreases in cell metabolism and cell viability. This study uses immunohistochemistry (IHC) to show the increased presence of CD68 …

The Role Of Calcium In Regulation Of Glial Cell Line Derived Neurotrophic Factor By Skeletal Muscle Cells, Alicia M. Boynton

Masters Theses

Glial cell line-derived neurotrophic factor (GDNF) is an important signaling molecule for the somatic motor nervous system. GDNF protein is produced and secreted by skeletal muscle cells and helps maintain motor neuron innervation at the neuromuscular junction. Treatment with exogenous GDNF prevents denervation which is characteristic of aging and neurodegenerative disease. The therapeutic potential of GDNF cannot be fully explored without understanding the mechanisms by which GDNF protein production is regulated. The primary objective of this study was to determine the role of calcium in regulating GDNF protein expression by skeletal muscle cells. Skeletal muscle cells (C2C12) were grown in …

First-In-Human Clinical Trial Of Oral Onc201 In Patients With Refractory Solid Tumors, Mark N. Stein, Joseph R. Bertino, Howard L. Kaufman, Tina M. Mayer, Rebecca A. Moss, Ann W. Silk, Nancy Chan, Jyoti Malhotra, Loma Rodriguez, Joseph Aisner, Robert Aiken, Bruce G. Haffty, Robert S. Dipaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Sioghan Dickerson, Ling Zheng, Wafik S. El-Deiry, Joshua E. Allen, Martin Stogniew, Wolfgang Oster, Janice M. Mehnert

Internal Medicine Faculty Publications

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D).

Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, …

Wisp1 Is An Overexpressed Driver Of Glioblastoma, Pushan R. Dasgupta

Dissertations and Theses (Open Access)

Despite current multimodal therapies for glioblastoma (GBM) the prognosis remains very grim. There is a tremendous need to identify new genetic drivers which can serve as potential therapeutic targets. In order to find new drivers, we leveraged genomic datasets to conduct a context specific in vivo functional genomic screen of overexpressed and/or amplified genes in GBM. We identified WISP1, a secreted extracellular matrix protein, to be an overexpressed driver in GBM. Overexpression of WISP1 was able to drive tumor growth in various in vivo models. Knockdown of WISP1 with shRNAs resulted in reduced colony formation in vitro and reduced tumor …

The Role Of Hemodynamic Force On Development Of The Mouse Embryonic Heart, Samantha Jean Fredrickson

Graduate Theses/Dissertations

The most common type of birth defects are congenital heart defects (or CHDs). Though a few cases of CHDs have been attributed to genetic defects specific to the heart, substance exposure, or to maternal disease, the cause of most CHDs is unknown. Thus, further research is needed to determine how CHDs form. Very few studies have investigated how physiological factors like perturbations of blood flow can affect normal heart development. For instance, increasing or decreasing the resistance to blood flow can alter development of the heart in both zebrafish and chicken embryos. This could be one mechanism to explain CHD …

Gcn5 Impacts Fgf Signaling At Multiple Levels And Activates C-Myc Target Genes During Early Differentiation Of Embryoid Bodies, Li Wang

Dissertations and Theses (Open Access)

Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages in vitro that parallel developmental events during embryogenesis in vivo. …

Intravenous Administration Of Iron Oxide Nanoparticles In The Chicken Model, Huong Thi Ngoc Le

Graduate Theses and Dissertations

To be used in health care, the safety and effectiveness of nanoparticles needs to be tested in a living organism. The objective of this project was to develop the chicken as a convenient animal model to examine tissue targeting of intravenously (i.v.)-injected iron oxide (IO) nanoparticles. In Experiment 1, different doses of IO-COOH were i.v. injected into chickens; blood was collected at 0, 5, 15, 30, and 60 minutes post-injection; liver, spleen, lung, and kidney were collected after the last blood collection. For Experiment 2, IO-COOH and IO-PEG were i.v. injected into chickens; blood and the organs were collected at …

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 …

Basigin-2 Mediated Activation Of Erk1/2 Signaling In Human Glioblastoma Multiforme Cells, Erik R. Peterson

All NMU Master's Theses

Glioblastoma multiforme (GBM) is the most common malignant form of human brain cancer. GBM tumor cells overexpress the protein Basigin (Bsg) at the cell surface where it contributes to malignancy via stimulation of matrix metalloproteinase (MMP) expression in surrounding normal tissues, resulting in the degradation of the extracellular matrix (ECM) surrounding tumors, promoting remodeling of the tumor borders, stimulating growth. In work by Belton et al. (2008), human uterine endometrial cells treated with a recombinant form of human basigin possessing the extracellular domain of the Bsg protein (rBsg-ECD) showed activation of the Mitogen-Activated Protein Kinase (MAPK) signaling pathway proteins, ERK1/2. …

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 …

A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virusinfected cells (30 min post infection). Expression of ORFV073 alone was sufficient to …

The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget

Graduate Theses/Dissertations

Throughout embryonic development, blood vessels are derived from endothelial cells by way of vasculogenesis. During angiogenesis, vessels remodel to form a hierarchy of large-diameter arteries that branch into small-diameter capillaries. In this maturation, vessels respond to unidentified signaling events to become surrounded with an outer layer of vascular smooth muscle cells (vSMCs). This results in arteries that have a thick vSMC layer, veins that have a thin vSMC layer, and capillaries that have a very thin or absent vSMC layer. What remains to be determined is the cause of the thicker layer of vSMCs around proximal arteries. Previous studies …