Genetics and Genomics Commons^™

Preoperative Stimulation Of Resolution And Inflammation Blockade Eradicates Micrometastases., Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M Gilligan, Megan L Sulciner, Swati S Bhasin, Diane R Bielenberg, Jaimie Chang, Birgitta A Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A Sparks, Steven J Staffa, Vidula Sukhatme, Bruce D Hammock, Mark W Kieran, Sui Huang, Manoj Bhasin, Charles N Serhan, Vikas P Sukhatme

Articles, Abstracts, and Reports

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 …

Downregulation Of Cenpf Remodels Prostate Cancer Cells And Alters Cellular Metabolism., Muhammad Shahid, Minhyung Kim, Min Young Lee, Austin Yeon, Sungyong You, Hyung L Kim, Jayoung Kim

Articles, Abstracts, and Reports

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the …

Participant Perspectives On A Phase I/Ii Ocular Gene Therapy Trial (Nct02077361), Stephanie P. Brooks, Shelly Benjaminy, Tania M. Bubela

Office of the Provost

Background: To learn from the experiences of potential clinical trial participants, participants in a Phase 1 ocular gene therapy trial, and their partners to improve communications and trial conduct.
Materials and methods: Primary and secondary qualitative analysis of semi-structured interviews of potential participants (n = 20), clinical trial participants (n = 2) and their partners (n = 2) in a gene therapy clinical trial for choroideremia (NCT02077361). Analysis included: 1) thematic analysis of transcribed entrance and exit semi-structured interviews with trial participants and their partners; and 2) secondary qualitative analysis of interviews with potential trial participants, …

Publisher Correction: Toxoplasma Modulates Signature Pathways Of Human Epilepsy, Neurodegeneration & Cancer., Huân M Ngô, Ying Zhou, Hernan Lorenzi, Kai Wang, Taek-Kyun Kim, Yong Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Seesandra V Rajagopala, Craig W Roberts, Fiona L Henriquez, Alexandre Montpetit, Jenefer M Blackwell, Sarra E Jamieson, Kelsey Wheeler, Ian J Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez, Roderick G Davis, Liliana Soroceanu, Charles Cobbs, Dennis A Steindler, Kenneth Boyer, A Gwendolyn Noble, Charles N Swisher, Peter T Heydemann, Peter Rabiah, Shawn Withers, Patricia Soteropoulos, Leroy Hood, Rima Mcleod

Articles, Abstracts, and Reports

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Toward A Comprehensive View Of Cancer Immune Responsiveness: A Synopsis From The Sitc Workshop., Davide Bedognetti, Michele Ceccarelli, Lorenzo Galluzzi, Rongze Lu, Karolina Palucka, Josue Samayoa, Stefani Spranger, Sarah Warren, Kwok-Kin Wong, Elad Ziv, Diego Chowell, Lisa M Coussens, Daniel D De Carvalho, David G Denardo, Jérôme Galon, Howard L Kaufman, Tomas Kirchhoff, Michael T Lotze, Jason J Luke, Andy J Minn, Katerina Politi, Leonard D Shultz, Richard Simon, Vésteinn Thórsson, Joanne B Weidhaas, Maria Libera Ascierto, Paolo Antonio Ascierto, James M Barnes, Valentin Barsan, Praveen K Bommareddy, Adrian Bot, Sarah E Church, Gennaro Ciliberto, Andrea De Maria, Dobrin Draganov, Winson S Ho, Heather M Mcgee, Anne Monette, Joseph F Murphy, Paola Nisticò, Wungki Park, Maulik Patel, Michael Quigley, Laszlo Radvanyi, Harry Raftopoulos, Nils-Petter Rudqvist, Alexandra Snyder, Randy F Sweis, Sara Valpione, Lisa H Butterfield, Mary L Disis, Bernard A Fox, Alessandra Cesano, Francesco M Marincola

Articles, Abstracts, and Reports

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes …

Clinical Utility Of Exon Deletion/Duplication Microarray Testing - A Children’S Mercy Kansas City Two-Year Experience, Binu Porath

Research Days

No abstract provided.

A Discrepancy Between The Human Reference Genome (Grch37) And Transcriptome (Refseq) Results In The Incorrect Annotation Of A Clinically-Relevant Sequence Variant In Recql4, Lisa A. Lansdon

Research Days

No abstract provided.

Rising Rural Body-Mass Index Is The Main Driver Of The Global Obesity Epidemic In Adults, Con Burns, Tara Coppinger, Janette Walton, Et Al

Publications

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to …

Extracellular Vesicle Encapsulated Micrornas In Patients With Type 2 Diabetes Are Affected By Metformin Treatment., Vikas Ghai, Taek-Kyun Kim, Alton Etheridge, Trine Nielsen, Torben Hansen, Oluf Pedersen, David Galas, Kai Wang

Articles, Abstracts, and Reports

Recently, microRNAs (miRNAs) in circulating extracellular vesicles (EVs), have emerged as a source of potential biomarkers for various pathophysiological conditions, including metabolic disorders such as diabetes. Type 2 diabetes mellitus (T2DM), is the most prevalent form of diabetes in the USA, with 30 million diagnosed patients. Identifying miRNA biomarkers that can be used to assess response to glucose lowering treatments would be useful. Using patient plasma samples from a subset of the Danish Metagenomics of the Human Intestinal Tract (MetaHIT) cohort, we characterized miRNAs from whole plasma, plasma-derived EVs, and EV-depleted plasma by small RNA-sequencing to identify T2DM associated miRNAs. …

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons, …

The Relationship Between Uncertainty Tolerance And Oncologists’ Perceptions Of Large-Panel Genomic Tumor Testing, Eric Anderson, Alexandra Hinton, Christine Lary, Kimberly Murray, Leo Waterson, Paul Han, Maine Cancer Genomics Initiative

MaineHealth Maine Medical Center

Introduction:

Large-panel genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise, but that currently poses many uncertainties regarding its clinical value and appropriate use. Uncertainty Tolerance (UT), a psychological construct that describes trait-level differences in individuals’ responses to uncertainty, may influence oncologists’ perceptions and attitudes regarding GTT.

Community Oncology Clinicians’ Knowledge, Beliefs, And Attitudes Regarding Genomic Tumor Testing, Eric Anderson, Alexandra Hinton, Kimberly Murray, Hayley Mandeville, Caitlin Gutheil, Leo Waterston, Lee Lucas, Christine Duarte, Christian Thomas, Susan Miesfeldt, Petra Helbig, Andrey Antov, Jens Rueter, Paul Han

MaineHealth Maine Medical Center

Introduction: Genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise. However, little is known about clinicians’ knowledge, beliefs, and attitudes regarding GTT, particularly in community oncology settings.

Physician-Patient Communication About Genomic Tumor Testing: Perceptions Of Oncology Providers, Hayley Mandeville, Eric Anderson, Kimberly Murray, Caitlin Gutheil, Leo Waterston, Lee Lucas, Christine Duarte, Christian Thomas, Susan Miesfeldt, Petra Helbig, Andrey Antov, Jens Rueter, Paul Han

MaineHealth Maine Medical Center

Background:

• Genomic tumor testing (GTT) is a new technology and a cornerstone of the “precision medicine” movement in cancer care.

• GTT uses next-generation genome sequencing technology to identify somatic variants in tumor cells.

• By identifying somatic variants that predict responses to cancer therapies, GTT can help tailor therapy to individual patients, making them more effective.

• However, due to the fact that GTT also detects many variants of uncertain significance, its clinical value is currently unproven.

• When using GTT, physicians counsel patients about both its benefits and its limitations, but the ideal goals and content of …

Weighted Pathway Genetic Load Analysis Of Hyperbilirubinemic Infants Indicates A Potential Genetic Component For Susceptibility To Bilirubin Neurotoxicity, Sean M. Riordan, Jean-Baptiste Lepichon, Steven Shapiro, John Cowden, Monica Villagullen, Laurence Thielemans, Dina Villanueva Garcia, Jesus Aguirre-Hernandez

Posters

Severe kernicterus spectrum disorder (KSD) is described as motor and auditory deficits resulting from brain damage caused by hyperbilirubinemia. The severity of HB does not always predict the severity of injury. The lack of a strong monogenetic link to susceptibility suggests bilirubin-induced brain damage may be due to impaired bilirubin response pathways. This poster describes work to use a modified pathway genetic load (mPGL) score method to perform a targeted genetic analysis of whole exome data from patients with various degrees of neonatal HB, with an ultimate goal of developing a neonatal screen to susceptibiltiy to bilirubin neurotoxicity.

Developing Technologically Advanced Research In Low- And Middle-Income Countries, Isa Abdulkadir, Tina Slusher, Fidelia Bode-Thomas, Sean Riordan, Jean-Baptiste Lepichon, Laila Hassan, Shehu Abdullahi, Akinyemi Ofakunrin, Stephen Oguche, Steven Shapiro, William Ogala

Posters

This poster presents a collaboration between a group of scientists in Nigeria and the USA in developing a genomic research project and the solutions adopted in tackling the ethical implications and partnership equity and ownership of such a project.

Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

BACKGROUND: Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer.

RESULTS: Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer …

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …

Male Determining Gene Nix May Bring An End To Transmission Of Diseases Through Mosquitoes, Mohammed Mahdi

Thinking Matters Symposium Archive

Female mosquitoes take blood from humans to gain protein needed to produce eggs, and in the process they can transmit viruses, such as Zika, Dengue, and chikungunya, or parasites, such as malaria. Male mosquitoes do not transmit diseases. This literature review will examine what is known about how sex is determined in mosquitoes and how this can be used to manipulate the females that spread diseases to humans. Using CRISPR Cas9, the lab of Zhijian Tu removed the Nix gene from mosquito embryos; all of these were feminized. Ectopic overexpression of Nix gene product in mosquito embryos caused even genetically …

The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks

Dissertations

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM.

Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran …

Medical Decision Making Among Individuals With A Variant Of Uncertain Significance In A Hereditary Cancer Gene And Those With A Chek2 Pathogenic Variant, Deanna J. Almanza

USF Tampa Graduate Theses and Dissertations

Despite national guidelines, women with a BRCA VUS or CHEK2 pathogenic variant are choosing to have risk-reducing surgeries such as bilateral mastectomies which are not aligned with their level of cancer risk based on genetic test results alone. Semi-structured telephone interviews were conducted with 6 women with a BRCA VUS and 12 with a CHEK2 pathogenic variant exploring the factors influencing their decision-making process when considering medical management options. Patients from a cancer registry agreed to a recorded telephone interview. Coding was performed using the main constructs from the Ottawa Patient Decision Guide including: knowledge, uncertainty, values, and support. Iterative …

Buparlisib In Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase Ii Trial., Patrick Y Wen, Mehdi Touat, Brian M Alexander, Ingo K Mellinghoff, Shakti Ramkissoon, Christine S Mccluskey, Kristine Pelton, Sam Haidar, Sankha S Basu, Sarah C Gaffey, Loreal E Brown, Juan Emmanuel Martinez-Ledesma, Shaofang Wu, Jungwoo Kim, Wei Wei, Mi-Ae Park, Jason T Huse, John G Kuhn, Mikael L Rinne, Howard Colman, Nathalie Y R Agar, Antonio M Omuro, Lisa M Deangelis, Mark R Gilbert, John F De Groot, Timothy F Cloughesy, Andrew S Chi, Thomas M Roberts, Jean J Zhao, Eudocia Q Lee, Lakshmi Nayak, James R Heath, Laura L Horky, Tracy T Batchelor, Rameen Beroukhim, Susan M Chang, Azra H Ligon, Ian F Dunn, Dimpy Koul, Geoffrey S Young, Michael D Prados, David A Reardon, W K Alfred Yung, Keith L Ligon

Articles, Abstracts, and Reports

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once …

Alterations In Phosphorylation Of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection., Elizabeth K K Glennon, Laura S Austin, Nadia Arang, Heather S Kain, Fred D Mast, Kamalakannan Vijayan, John D Aitchison, Stefan H I Kappe, Alexis Kaushansky

Articles, Abstracts, and Reports

Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated ribosomal protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast …

Comparing Family Sharing Behaviors In Brca Carriers With Palb2 Carriers, Joy E. Kechik

USF Tampa Graduate Theses and Dissertations

Identifying individuals with hereditary cancer predisposition can improve health outcomes for patients and their family members through early cancer detection and prevention strategies. Prior research about family sharing of genetic test results among those with hereditary breast cancer has overwhelmingly been limited to the BRCA1 and BRCA2 genes. The present study sought to compare family sharing behaviors in women with pathogenic BRCA variants to women with pathogenic variants in the more recently identified and characterized PALB2 gene. A total of 18 BRCA carriers and 13 PALB2 carriers were interviewed about family sharing practices using a semi-structured guide based on the …

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b^−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In …

Genetic Interaction Analysis Among Oncogenesis-Related Genes Revealed Novel Genes And Networks In Lung Cancer Development, Yafang Li, Xiangjun Xiao, Yohan Bossé, Olga Gorlova, Ivan Gorlov, Younghun Han, Jinyoung Byun, Natasha Leighl, Jakob S. Johansen, Matt Barnett, Chu Chen, Gary Goodman, Angela Cox, Fiona Taylor, Penella Woll, H. Erich Wichmann, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Jiali Han, Katherine Siminovitch, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria

Markey Cancer Center Faculty Publications

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified …

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

Adipose-Derived Autotaxin Regulates Inflammation And Steatosis Associated With Diet-Induced Obesity, J. Anthony Brandon, Maria Kraemer, Julia Vandra, Suchismita Halder, Margo F. Ubele, Andrew J. Morris, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Autotaxin (ATX) is a secreted enzyme that generates the bioactive lipid lysophosphatidic acid (LPA). We generated mice with global inducible post-natal inactivation or adipose-specific loss of the Enpp2 gene encoding ATX. The animals are phenotypically unremarkable and exhibit differences in adipocyte size and adipose tissue expression of inflammatory genes after high fat feeding without gross differences in fat distribution or body mass. Surprisingly, both models of Enpp2- deficiency exhibited marked protection from high fat diet-induced hepatic steatosis. This phenotype was not associated with differences in dietary fat absorption but may be accounted for by differences in hepatic expression of …

Mitf Has A Central Role In Regulating Starvation-Induced Autophagy In Melanoma., Katrin Möller, Sara Sigurbjornsdottir, Asgeir O Arnthorsson, Vivian Pogenberg, Ramile Dilshat, Valerie Fock, Solveig H Brynjolfsdottir, Christian Bindesboll, Margret Bessadottir, Helga M Ogmundsdottir, Anne Simonsen, Lionel Larue, Matthias Wilmanns, Vesteinn Thorsson, Eirikur Steingrimsson, Margret H Ogmundsdottir

Articles, Abstracts, and Reports

The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, …

Shared Heritability And Functional Enrichment Across Six Solid Cancers, Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez

Markey Cancer Center Faculty Publications

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r_g = 0.57, p = 4.6 × 10⁻⁸), breast and ovarian cancer (r_g = 0.24, p = 7 × 10^{−5 …}