Cell and Developmental Biology Commons^™

Sarcoid-Like Reaction Associated With Renal Cell Carcinoma - A Case Report., Asma Iftikhar, Muhammad A I Cheema, Preethi Ramachandran, Sonu Sahni

Touro College of Osteopathic Medicine (New York) Publications and Research

Renal cell carcinoma (RCC) is a highly vascular tumor, which may spread to the lungs and other organs. It often presents with localized or systemic manifestation, including paraneoplastic syndromes. Sarcoidosis is a systemic granulomatous inflammatory disease characterized by non-caseating granulomas that typically afflicts the respiratory system. In the absence of any evidence of systemic sarcoidosis they are referred to as sarcoid-like reactions. Non-caseating epithelioid granulomas, also regarded to sarcoid-like granulomas have been described in association with certain malignancies such as carcinomas of the breast, colon, seminoma, and Hodgkin's lymphoma. However, sarcoid like reaction associated with renal cell carcinoma is uncommon. …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

Diffuse Intrinsic Pontine Glioma Cells Are Vulnerable To Low Intensity Electric Fields Delivered By Intratumoral Modulation Therapy, Andrew Deweyert, Erin Iredale, Hu Xu, Eugene Wong, Susanne Schmid, Matthew O. Hebb

Anatomy and Cell Biology Publications

Introduction

Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT).

Methods

DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. …

Double Deletion Of Panx1 And Panx3 Affects Skin And Bone But Not Hearing, J M. Abitbol, B L. O'Donnell, C B. Wakefield, E Jewlal, J J. Kelly, K Barr, K E. Willmore, B. L. Allman, S Penuela

Anatomy and Cell Biology Publications

Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. To evaluate the roles of Panx1 and Panx3 in the skin, bone, and cochlea, we created the first Panx1/Panx3 double knock-out mouse model (dKO). …

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov

Anatomy and Cell Biology Publications

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid …

First M87 Event Horizon Telescope Results. I. The Shadow Of The Supermassive Black Hole, Aaron Faber, Kazunori Akiyama, Antxon Alberdi, Walter Alef, Keiichi Asada, Rebecca Azulay, Anne-Kathrin Baczko, David Ball, Mislav Baloković, John Barrett, Dan Bintley

Anatomy and Cell Biology Publications

When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, …

The Connexin 30 A88v Mutant Reduces Cochlear Gap Junction Expression And Confers Long-Term Protection Against Hearing Loss, John J. Kelly, Julia Abitbol, Stephanie Hulme, Eric R. Press, Dale Laird, Brian L. Allman

Anatomy and Cell Biology Publications

Mutations in the genes that encode the gap junction proteins connexin 26 (Cx26, encoded by GJB2) and Cx30 (GJB6) are the leading cause of hereditary hearing loss. That said, the Cx30 p.Ala88Val (A88V) mutant causes Clouston syndrome, but not hearing loss. Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30(A88V/A88V) mice. During early development, there were no overt structural differences in the cochlea between genotypes, including a normal complement of hair cells; however, the supporting cell Cx30 gap junction plaques in mutant …

Inhibition Of Pannexin 1 Reduces The Tumorigenic Properties Of Human Melanoma Cells, Taylor J. Freeman, Samar Sayedyahossein, Rafael E. Sanchez-Pupo, Brooke O'Donnell, Kenneth Huang, Zameena Lakhani, Daniel Nouri-Nejad, Kevin J. Barr, Luke Harland, Steven Latosinsky, Aaron Grant, Lina Dagnino, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment …

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice, Claire C. Young, Ryan M. Baker, Christopher J. Howlett, Todd Hryciw, Joshua E. Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L. Pin

Anatomy and Cell Biology Publications

Female mice lacking ATRX in the pancreas have increased sensitivity to pancreatic cancer, whereas male mice without ATRX are protected. This study identifies such susceptibility in pancreatic cancer and highlights the need for sex-specific approaches in cancer treatment. BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler.-thalassemia, mental-retardation, …

Insulin-Like Growth Factor Binding Protein-6 Promotes The Differentiation Of Placental Mesenchymal Stem Cells Into Skeletal Muscle Independent Of Insulin-Like Growth Factor Receptor-1 And Insulin Receptor., Doaa Aboalola, Victor K M Han

Anatomy and Cell Biology Publications

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation,

The Role Of Serum Histones In Canine Heat Stroke, Jenna Acutt

Scripps Senior Theses

Rising temperatures all over the world has correlated with more frequent heat stroke related injuries and death. This statistic not only applies to humans, but to canines as well, who have similar body temperature thresholds. Recent studies have demonstrated that serum histones, released after cell death from heat stroke, play a role in heat stroke related injuries and death. This proposal aims to determine the severity of the effects caused by serum histone release after heat stroke by exposing selected canine cell lines to cell lysate and purified histones H2A, H2B, H3, and H4, which have been found to be …

Intratumoral Delivery Of Plasmid Il12 Via Electroporation Leads To Regression Of Injected And Noninjected Tumors In Merkel Cell Carcinoma, Shailender Bhatia, Natalie V. Longino, Natalie J. Miller, Rima Kulikauskas, Jayasri G. Iyer, Dafina Ibrani, Astrid Blom, David R. Byrd, Upendra Parvathaneni, Christopher Twitty, Jean S. Campbell, Mai H. Le, Sharron Gargosky, Robert H. Pierce, Richard Heller, Adil Daud, Paul Nghiem

Bioelectrics Publications

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.

Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. …

Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori

Bioelectrics Publications

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of …

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu

Theses and Dissertations

In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically achievable enterohepatic …

A 3d Bioprinter Platform For Mechanistic Analysis Of Tumoroids And Chimeric Mammary Organoids, John A. Reid, Xavier-Lewis Palmer, Peter A. Mollica, Nicole Northam, Patrick C. Sachs, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise …

A Developmental Study Of Apoptotic Markers And Histamine In Cephalopod Statocysts, Samantha Nicole Leef

Honors Theses and Capstones

Cephalopods can participate in complex navigation using landmarks that show context due to their statocysts. Statocysts are analogous to the vertebrate vestibular and auditory system encased in cartilage rather than bone making them more easily accessible. Age and anatomical dysfunctions are the reasons for many human vestibular malfunctions. Two of these sources are endolymph hydrops and aging. In the past, endolymph pressure changes were attributed to the ineffectual ion transport. Recent studies have illuminated the possibility of histamine receptors in the semicircular canal could be responsible for patients’ endolymph pressure changes rather than the previous belief that the pressure changes …

Erbb3 Signaling And Its Effect On Spheroid Formation In Ovarian Cancer, Muskan Bansal, Danielle Burke, Mara P. Steinkamp

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

ErbB3 is a receptor tyrosine kinase in the epidermal growth factor receptor (EGFR) family. Like other family members, it has an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. ErbB3 requires interactions with other receptors and dimerizes with ErbB2 and MET, to activate downstream signaling pathways. Mutations in the ErbB3 gene within the extracellular and kinase domains have been identified in many cancer types. To understand the impact of ErbB3 on cancer growth and metastasis, the human ovarian cancer cell line, OVCAR8, was used as a model. Parental OVCAR8 cells that express ErbB2 and ErbB3 were compared …

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

Novel Amphiphilic Cyclobutene And Cyclobutane Cis-C18 Fatty Acid Derivatives Inhibit Mycobacterium Avium Subsp. Paratuberculosis Growth, Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin T. Sakallioglu, Robert Powers, Patrick H. Dussault, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of Johne’s disease in ruminants and has been associated with Crohn’s disease in humans. An effective control of Map by either vaccines or chemoprophylaxis is a paramount need for veterinary and possibly human medicine. Given the importance of fatty acids in the biosynthesis of mycolic acids and the mycobacterial cell wall, we tested novel amphiphilic C₁₀ and C₁₈ cyclobutene and cyclobutane fatty acid derivatives for Map inhibition. Microdilution minimal inhibitory concentrations (MIC) with 5 or 7 week endpoints were measured in Middlebrook 7H9 base broth media. We compared the …

Investigation Of Congestive Heart Failure In Beef Cattle In A Feedyard At A Moderate Altitude In Western Nebraska, Rodney A. Moxley, David R. Smith, Dale M. Grotelueschen, Tom Edwards, David Steffen

School of Veterinary and Biomedical Sciences: Faculty Publications

Right-sided congestive heart failure (brisket disease) commonly occurs in cattle raised at elevations >2,500– 3,500 m. We investigated clinical cases resembling brisket disease at a western Nebraska feedyard at a moderate altitude (1,369 m). Over a 15-mo period (2009–2010), we examined 17 cases (16 steers and 1 heifer), all purebred Angus. All animals had clinical right-sided heart failure: brisket and ventral abdominal edema, and severe chronic passive congestion of the liver. Gross examination confirmed right ventricular hypertrophy (left ventricle plus septum: right ventricle weight ratio mean: 1.33 vs. 2.8–4.0 reference interval). Microscopically, all 17 cases had interstitial fibrosis (mean score: …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Monocytes And Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures In Experimental Model Of Multiple Sclerosis, Kelly L. Monaghan, Wen Zheng, Gangqing Hu, Edwin C. K. Wan

Faculty & Staff Scholarship

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6Chi monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis …

Ehdv-2 Infection Prevalence Varies In Culicoides Sonorensis After Feeding On Infected White-Tailed Deer Over The Course Of Viremia, Sandra Y. Mendiola, Mary K. Mills, Elin Maki, Barbara S. Drolet, William C. Wilson, Roy D. Berghaus, David E. Stallknecht, Jonathan Breitenbach, D. Scott Mcvey, Mark G. Ruder

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease viruses (EHDVs) are arboviral pathogens of white-tailed deer and other wild and domestic ruminants in North America. Transmitted by various species of Culicoides, EHDVs circulate wherever competent vectors and susceptible ruminant host populations co-exist. The impact of variation in the level and duration of EHDV viremia in white-tailed deer (Odocoileus virginianus) on Culicoides infection prevalence is not well characterized. Here we examined how infection prevalence in a confirmed North American vector of EHDV-2 (Culicoides sonorensis) varies in response to fluctuations in deer viremia. To accomplish this, five white-tailed deer were experimentally infected with EHDV-2 and colonized C. …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

Put Your Money Where Your Mouth Is: Reforming Organized Dentistry To Address Persistent Oral Health Disparities In The U.S., Aparna Chintapalli

Pomona Senior Theses

The importance of oral health has been largely neglected from the conventional standards of healthcare in terms of public understanding & prioritization, the industrial infrastructure, and the scope of prevention & early-intervention services. Its adjunctive locus to the field of medicine has lead to the bifurcation of the oral cavity from the rest of the human body. As a result of this divide, there have been multiple factors that have allowed socially stratified oral health outcomes to manifest. This thesis examines the determinants of oral health disparities through a multidisciplinary lens (i.e. biology, public policy, infrastructure), and offers evidence of …

Optimization Of Primary Cilia Detection In Musculoskeletal Tissue, Ragen Engel

Williams Honors College, Honors Research Projects

The objective of this research project was to optimize a laboratory technique for visualizing primary cilia in musculoskeletal tissue of young swine, specifically the growth plate of long bones. This was accomplished through varying fixation procedures, antigen retrieval methods, antibody concentrations, and incubation times. By varying these parameters, a reproducible procedure was developed to examine the primary cilia in multiple tissues including ligament, fascia, and growth plate. This experiment introduced variances in fixation methods, with methanol or formalin. Paraffin and frozen embedding techniques were also varied for comparison with regards to cilia visualization. Results from the acetylated alpha tubulin (aTUB) …

Sprouty4 Is A Negative Regulator Of Erk/Mapk Signaling In Breast Cancer And Plays A Role In The Transition From In Situ To Invasive Disease, Ethan Brock

Wayne State University Dissertations

Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Previous data by our group found that Sprouty4 transcript was differentially expressed between three DCIS cell lines and a non-transformed breast epithelial cell line. Sprouty proteins are important regulators of ERK/MAPK signaling, and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry we …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

Sonic Hedgehog Is Expressed By Hilar Mossy Cells And Regulates Cellular Survival And Neurogenesis In The Adult Hippocampus, Luis E. Gonzalez-Reyes, Chia-Chu Chiang, Mingming Zhang, Joshua Johnson, Manuel Arrillaga-Tamez, Nicholas H. Couturier, Neha Reddy, Lev Starikov, Jeffrey R. Capadona, Andreas H. Kottmann, Dominique M. Durand

Publications and Research

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration …

P4ha1 Is A New Regulator Of The Hif-1 Pathway In Breast Cancer, Ren Xu

Markey Cancer Center Faculty Publications

Hypoxia-Inducible Factor (HIF)-1 is a transcription factor that plays the key role in response to low oxygen concentrations, or hypoxia. Activation of the HIF-1 pathway is not only crucial for normal tissue development and function, but also involved in disease progression, such as cancer. Cancer cells proliferate rapidly in solid tumors, and thus, solid tumors consume much more oxygen and nutrients than normal tissue and generate oxygen tension. It is well established that oxygen tension in solid tumor tissue induces the aberrant activation of the HIF-1 pathway, and subsequently promotes angiogenesis and tumor progression. Breast cancer is a heterogeneous disease …