Department of Genetics Publications from Jan. 27 – Feb. 9, 2019

February 11, 2019

Department of Genetics faculty, postdocs, students and collaborators published eleven papers during January 27 – February 9, 2019.

 

Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
de Vries PS, Brown MR, Bentley AR, Sung YJ, Winkler TW, Ntalla I, Schwander K, Kraja AT, Guo X, Franceschini N, Cheng CY, Sim X, Vojinovic D, Huffman JE, Musani SK, Li C, Feitosa MF, Richard MA, Noordam R, Aschard H, Bartz TM, Bielak LF, Deng X, Dorajoo R, Lohman KK, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Evangelou E, Graff M, Alver M, Boissel M, Chai JF, Chen X, Divers J, Gandin I, Gao C, Goel A, Hagemeijer Y, Harris SE, Hartwig FP, He M, Horimoto ARVR, Hsu FC, Jackson AU, Kasturiratne A, Komulainen P, Kühnel B, Laguzzi F, Lee JH, Luan J, Lyytikäinen LP, Matoba N, Nolte IM, Pietzner M, Riaz M, Said MA, Scott RA, Sofer T, Stancáková A, Takeuchi F, Tayo BO, van der Most PJ, Varga TV, Wang Y, Ware EB, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Amin N, Amini M, Arking DE, Aung T, Ballantyne C, Boerwinkle E, Broeckel U, Campbell A, Canouil M, Charumathi S, Chen YI, Connell JM, de Faire U, de Las Fuentes L, de Mutsert R, de Silva HJ, Ding J, Dominiczak AF, Duan Q, Eaton CB, Eppinga RN, Faul JD, Fisher V, Forrester T, Franco OH, Friedlander Y, Ghanbari M, Giulianini F, Grabe HJ, Grove ML, Gu CC, Harris TB, Heikkinen S, Heng CK, Hirata M, Hixson JE, Howard BV, Ikram MA; InterAct Consortium, Jacobs DR Jr, Johnson C, Jonas JB, Kammerer CM, Katsuya T, Khor CC, Kilpeläinen TO, Koh WP, Koistinen HA, Kolcic I, Kooperberg C, Krieger JE, Kritchevsky SB, Kubo M, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lemaitre RN, Li Y, Liang J, Liu J, Liu K, Loh M, Louie T, Mägi R, Manichaikul AW, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Mosley TH Jr, Mukamal KJ, Nalls MA, Nauck M, Nelson CP, Sotoodehnia N, O’Connell JR, Palmer ND, Pazoki R, Pedersen NL, Peters A, Peyser PA, Polasek O, Poulter N, Raffel LJ, Raitakari OT, Reiner AP, Rice TK, Rich SS, Robino A, Robinson JG, Rose LM, Rudan I, Schmidt CO, Schreiner PJ, Scott WR, Sever P, Shi Y, Sidney S, Sims M, Smith BH, Smith JA, Snieder H, Starr JM, Strauch K, Tan N, Taylor KD, Teo YY, Tham YC, Uitterlinden AG, van Heemst D, Vuckovic D, Waldenberger M, Wang L, Wang Y, Wang Z, Wei WB, Williams C, Wilson G Sr, Wojczynski MK, Yao J, Yu B, Yu C, Yuan JM, Zhao W, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Deary IJ, Esko T, Farrall M, Franks PW, Freedman BI, Froguel P, Gasparini P, Gieger C, Horta BL, Kamatani Y, Kato N, Kooner JS, Laakso M, Leander K, Lehtimäki T; Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), Magnusson PKE, Penninx B, Pereira AC, Rauramaa R, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wang YX, Wareham NJ, Watkins H, Weir DR, Wickremasinghe AR, Zheng W, Elliott P, North KE, Bouchard C, Evans MK, Gudnason V, Liu CT, Liu Y, Psaty BM, Ridker PM, van Dam RM, Kardia SLR, Zhu X, Rotimi CN, Mook-Kanamori DO, Fornage M, Kelly TN, Fox ER, Hayward C, van Duijn CM, Tai ES, Wong TY, Liu J, Rotter JI, Gauderman WJ, Province MA, Munroe PB, Rice K, Chasman DI, Cupples LA, Rao DC, Morrison AC.
Am J Epidemiol. 2019 Jan 29. doi: 10.1093/aje/kwz005. [Epub ahead of print]
PMID: 30698716

 

A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.
Schork AJ, Won H, Appadurai V, Nudel R, Gandal M, Delaneau O, Revsbech Christiansen M, Hougaard DM, Bækved-Hansen M, Bybjerg-Grauholm J, Giørtz Pedersen M, Agerbo E, Bøcker Pedersen C, Neale BM, Daly MJ, Wray NR, Nordentoft M, Mors O, Børglum AD, Bo Mortensen P, Buil A, Thompson WK, Geschwind DH, Werge T.
Nat Neurosci. 2019 Jan 28. doi: 10.1038/s41593-018-0320-0. [Epub ahead of print]
PMID: 30692689

 

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, Coleman JRI, Hagenaars SP, Ward J, Wigmore EM, Alloza C, Shen X, Barbu MC, Xu EY, Whalley HC, Marioni RE, Porteous DJ, Davies G, Deary IJ, Hemani G, Berger K, Teismann H, Rawal R, Arolt V, Baune BT, Dannlowski U, Domschke K, Tian C, Hinds DA; 23andMe Research Team; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Trzaskowski M, Byrne EM, Ripke S, Smith DJ, Sullivan PF, Wray NR, Breen G, Lewis CM, McIntosh AM.
Nat Neurosci. 2019 Feb 4. doi: 10.1038/s41593-018-0326-7. [Epub ahead of print]
PMID: 30718901

 

The genomics of major psychiatric disorders in a large pedigree from Northern Sweden.
Szatkiewicz J, Crowley JJ, Adolfsson AN, Åberg KA, Alaerts M, Genovese G, McCarroll S, Del-Favero J, Adolfsson R, Sullivan PF.
Transl Psychiatry. 2019 Feb 4;9(1):60. doi: 10.1038/s41398-019-0414-9.
PMID: 30718465

 

Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the “dark side” of addiction.
Peng Q, Bizon C, Gizer IR, Wilhelmsen KC, Ehlers CL.
Transl Psychiatry. 2019 Feb 4;9(1):71. doi: 10.1038/s41398-019-0397-6.
PMID: 30718457

 

Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer.
Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V, Akbani R, Bowlby R, Wong CK, Wiznerowicz M, Sanchez-Vega F, Robertson AG, Schneider BG, Lawrence MS, Noushmehr H, Malta TM; Cancer Genome Atlas Network, Stuart JM, Benz CC, Laird PW.
Cell. 2018 Apr 5;173(2):291-304.e6. doi: 10.1016/j.cell.2018.03.022.
PMID: 29625048

 

Cells exhibiting strong <i>p16</i> <sup><i>INK4a</i></sup> promoter activation in vivo display features of senescence.
Liu JY, Souroullas GP, Diekman BO, Krishnamurthy J, Hall BM, Sorrentino JA, Parker JS, Sessions GA, Gudkov AV, Sharpless NE.
Proc Natl Acad Sci U S A. 2019 Jan 25. pii: 201818313. doi: 10.1073/pnas.1818313116. [Epub ahead of print]
PMID: 30683717

 

Evaluating the Clinical Validity of Hypertrophic Cardiomyopathy Genes.
Ingles J, Goldstein J, Thaxton C, Caleshu C, Corty EW, Crowley SB, Dougherty K, Harrison SM, McGlaughon J, Milko LV, Morales A, Seifert BA, Strande N, Thomson K, van Tintelen JP, Wallace K, Walsh R, Wells Q, Whiffin N, Witkowski L, Semsarian C, Ware JS, Hershberger RE, Funke B.
Circ Genom Precis Med. 2019 Jan 25. doi: 10.1161/CIRCGEN.119.002460. [Epub ahead of print]
PMID: 30681346

 

Single-cell transcriptomic analysis of mouse neocortical development.
Loo L, Simon JM, Xing L, McCoy ES, Niehaus JK, Guo J, Anton ES, Zylka MJ.
Nat Commun. 2019 Jan 11;10(1):134. doi: 10.1038/s41467-018-08079-9.
PMID: 30635555

 

H3K9 Promotes Under-Replication of Pericentromeric Heterochromatin in Drosophila Salivary Gland Polytene Chromosomes.
Armstrong RL, Penke TJR, Chao SK, Gentile GM, Strahl BD, Matera AG, McKay DJ, Duronio RJ.
Genes (Basel). 2019 Jan 29;10(2). pii: E93. doi: 10.3390/genes10020093.
PMID: 30700014

 

Lysine 27 of replication-independent histone H3.3 is required for Polycomb target gene silencing but not for gene activation.
Leatham-Jensen M, Uyehara CM, Strahl BD, Matera AG, Duronio RJ, McKay DJ.
PLoS Genet. 2019 Jan 30;15(1):e1007932. doi: 10.1371/journal.pgen.1007932. [Epub ahead of print]
PMID: 30699116

 



Bradford Powell, MD, PhD, FACMG Appointed Assistant Professor in Department of Genetics

February 8, 2019

Dr. Powell’s research interests are focused on advancing transformative technological solutions to overcome the barriers of big data that have slowed progress toward effective implementation of genomic medicine.  Given his training as a clinical geneticist, pediatrician and bioinformatician, he is uniquely qualified to bridge the gap with cooperative research groups and cross-institutional consortia.

Bradford received a BS in Applied Biology from Georgia Institute of Technology in 1998, followed by a PhD in Genetics and Molecular Biology (2005) and an MD degree from UNC (2007).  After a Pediatrics residency at University of Florida (2010), he completed a Medical Genetics residency (2012), clinical genetics academic research fellowship and postdoctoral fellowship (2013) at Baylor College of Medicine.  Bradford joined UNC in 2013 as a Clinical Assistant Professor in Genetics with a secondary appointment in Medicine (Division of Hematology-Oncology).  In his team approach to translational research, he serves as co-PI on NCGENES, directing the informatics aspects of the project.  With NCNEXUS, he serves on the committee to determine which gene-disease associations have sufficient evidence for pre-symptomatic actionability, along with directing computational filtering and prioritization of genetic variants for presentation to expert analysts.  As part of the NIH ClinGen consortium, Bradford plays a central role in the Date Modeling Working Group and serves as co-chair of the ClinGen Pediatric Actionability Working Group.  He is also active in the Adult and Cancer Genetics clinics at UNC Hospitals and is active in teaching medical students as the director of the Genetics Coil.

The Department of Genetics is pleased to welcome Dr. Powell!

Bradford is located in 5078 Genetic Medicine Building and can be reached at 919-962-4916.



Katherine Hoadley, PhD Appointed Assistant Professor in Department of Genetics

February 8, 2019

Dr. Hoadley’s research interests are focused on using genomics-based assays and analyses to understand tumor heterogeneity, determine tissue-specific effects of genomic alterations, and develop genomic predictors of response or resistance to therapy. Her graduate work on breast cancer and postgraduate work with the Cancer Genome Atlas (TCGA) developed her informatics skills to approach these research interests.

Katie received her BA in Chemistry and BS in Biology from West Virginia Wesleyan College in 2001 and her PhD in Genetics and Molecular Biology from UNC in 2006. Following a postdoctoral fellowship at Netherlands Cancer Institute, she returned to UNC for further postdoctoral work in the Lineberger Comprehensive Cancer Center and was subsequently appointed as a Research Associate. She was named to the fixed-term faculty in Genetics in 2013 and became an LCCC member in 2014, as part of the Cancer Genetics Program. Since 2017, she has served as Associate Director of Cancer Genomics for the High-Throughput Sequencing Facility. She has worked with the Cancer Genome Atlas (TCGA) program for the past twelve years, taking on increasing levels of responsibility, including the co-chair of the testicular germ cell tumor project (Cell Reports, 2018) and a Steering Committee member for our 33 tumor type Pan-cancer Atlas project (26 papers published in Cell family journals April 2018). Katie is a member of the Computational Medicine program at UNC and her future research will use the wealth of knowledge available from the vast amount of data already in the public domain to continue to genomically characterize human tumors with the goal of developing even more powerful predictors of prognosis and benefit of therapeutics.

The Department of Genetics is pleased to welcome Dr. Hoadley!

Katie is located in 5212 Marsico Hall and can be reached at 919-962-8416.



Mohlke named Associate Chair for Research in the Department of Genetics

February 5, 2019

Karen L. Mohlke, PhD, has been named Associate Chair for Research in the Department of Genetics.

Dr. Karen L. Mohlke, Professor (Department of Genetics) has been named the Associate Chair for Research by Dr. Fernando Pardo Manuel de Villena, Chair of the department, effective February 1, 2019.  Karen joined the Department of Genetics in 2004 after serving as a postdoctoral fellow in the laboratory of Dr. Francis Collins at NHGRI.  She is a member of the Lineberger Comprehensive Cancer Center, teaching faculty for the Genetics and Molecular Biology (GMB) and Bioinformatics and Computational Biology (BCB) curricula, a member of the McAllister Heart Institute and was named an Oliver Smithies Investigator in 2016.

Mohlke maintains a very active and well-funded research program and has consistently been recognized by Thomson Reuters and Clarivate Analytics as a world-class researcher with highly cited papers ranking in the top one percent by citations for her field.  She is very active in mentoring women in science as evidenced by her service on faculty, postdoctoral and graduate student advisory committees.  In her new role, she will serve in a senior leadership and advisory role to the Genetics Chair.



Yuliya Pylayeva-Gupta Awarded Grant from V Foundation for Cancer Research

February 5, 2019

Yuliya Pylayeva-Gupta, PhD (Assistant Professor) is the PI on a new award from the V Foundation for Cancer Research.

 

The project titled “Mechanisms of pancreatic cancer-driven re-programming of tumor promoting B lymphocytes” is focused on elucidating molecular mechanisms by which pancreatic cancer promotes formation of and induces cytokine production in regulatory B cells.  Yuliya’s laboratory has demonstrated that B cells expressing the immunomodulatory cytokine IL35 are necessary to support the growth of PDAC in murine models and that IL35 suppresses anti-tumor immune responses and promotes resistance to immunotherapy in PDAC.  In Aim 1, they will clarify how B cell receptor (BCR) and endosomal Toll-like Receptor (TLR) signaling contribute to induction of IL35 expression in tumor-reactive B cells. To accomplish this task, they will analyze mouse models expressing a fixed BCR with or without antigen exposure, as well as mouse models lacking TLR signaling in B cells. The lab will also perform signaling pathway analysis in primary B cells and B cell lines. In Aim 2, they will define the role for IL35 in promoting regulatory cell development and function in PDAC using B cell specific knockout of IL35 and ex vivo signaling analyses in B cells. The proposed research will provide an understanding of a previously uncharacterized facet of B cell-mediated function in PDAC by using state-of-the-art PDAC murine models to test strategies that block immune suppressive pathways in the tumor microenvironment. This project will expand our understanding of how IL35 shapes the immunosuppressive tumor microenvironment and may inform the optimal design of B cell-directed immunotherapy strategies against pancreatic cancer.



Department of Genetics Publications for Jan. 13-26, 2019

January 28, 2019

Department of Genetics faculty, postdocs, students and collaborators published seven papers during January 13-26, 2019.

 

Improved Indel Detection in DNA and RNA via Realignment with ABRA2.
Mose LE, Perou CM, Parker JS.
Bioinformatics. 2019 Jan 15. doi: 10.1093/bioinformatics/btz033. [Epub ahead of print]
PMID: 30649250

 

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
Liu M, Jiang Y, Wedow R, Li Y, Brazel DM, Chen F, Datta G, Davila-Velderrain J, McGuire D, Tian C, Zhan X; 23andMe Research Team; HUNT All-In Psychiatry, Choquet H, Docherty AR, Faul JD, Foerster JR, Fritsche LG, Gabrielsen ME, Gordon SD, Haessler J, Hottenga JJ, Huang H, Jang SK, Jansen PR, Ling Y, Mägi R, Matoba N, McMahon G, Mulas A, Orrù V, Palviainen T, Pandit A, Reginsson GW, Skogholt AH, Smith JA, Taylor AE, Turman C, Willemsen G, Young H, Young KA, Zajac GJM, Zhao W, Zhou W, Bjornsdottir G, Boardman JD, Boehnke M, Boomsma DI, Chen C, Cucca F, Davies GE, Eaton CB, Ehringer MA, Esko T, Fiorillo E, Gillespie NA, Gudbjartsson DF, Haller T, Harris KM, Heath AC, Hewitt JK, Hickie IB, Hokanson JE, Hopfer CJ, Hunter DJ, Iacono WG, Johnson EO, Kamatani Y, Kardia SLR, Keller MC, Kellis M, Kooperberg C, Kraft P, Krauter KS, Laakso M, Lind PA, Loukola A, Lutz SM, Madden PAF, Martin NG, McGue M, McQueen MB, Medland SE, Metspalu A, Mohlke KL, Nielsen JB, Okada Y, Peters U, Polderman TJC, Posthuma D, Reiner AP, Rice JP, Rimm E, Rose RJ, Runarsdottir V, Stallings MC, Stančáková A, Stefansson H, Thai KK, Tindle HA, Tyrfingsson T, Wall TL, Weir DR, Weisner C, Whitfield JB, Winsvold BS, Yin J, Zuccolo L, Bierut LJ, Hveem K, Lee JJ, Munafò MR, Saccone NL, Willer CJ, Cornelis MC, David SP, Hinds DA, Jorgenson E, Kaprio J, Stitzel JA, Stefansson K, Thorgeirsson TE, Abecasis G, Liu DJ, Vrieze S.
Nat Genet. 2019 Jan 14. doi: 10.1038/s41588-018-0307-5. [Epub ahead of print]
PMID: 30643251

 

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
Kilpeläinen TO, Bentley AR, Noordam R, Sung YJ, Schwander K, Winkler TW, Jakupović H, Chasman DI, Manning A, Ntalla I, Aschard H, Brown MR, de Las Fuentes L, Franceschini N, Guo X, Vojinovic D, Aslibekyan S, Feitosa MF, Kho M, Musani SK, Richard M, Wang H, Wang Z, Bartz TM, Bielak LF, Campbell A, Dorajoo R, Fisher V, Hartwig FP, Horimoto ARVR, Li C, Lohman KK, Marten J, Sim X, Smith AV, Tajuddin SM, Alver M, Amini M, Boissel M, Chai JF, Chen X, Divers J, Evangelou E, Gao C, Graff M, Harris SE, He M, Hsu FC, Jackson AU, Zhao JH, Kraja AT, Kühnel B, Laguzzi F, Lyytikäinen LP, Nolte IM, Rauramaa R, Riaz M, Robino A, Rueedi R, Stringham HM, Takeuchi F, van der Most PJ, Varga TV, Verweij N, Ware EB, Wen W, Li X, Yanek LR, Amin N, Arnett DK, Boerwinkle E, Brumat M, Cade B, Canouil M, Chen YI, Concas MP, Connell J, de Mutsert R, de Silva HJ, de Vries PS, Demirkan A, Ding J, Eaton CB, Faul JD, Friedlander Y, Gabriel KP, Ghanbari M, Giulianini F, Gu CC, Gu D, Harris TB, He J, Heikkinen S, Heng CK, Hunt SC, Ikram MA, Jonas JB, Koh WP, Komulainen P, Krieger JE, Kritchevsky SB, Kutalik Z, Kuusisto J, Langefeld CD, Langenberg C, Launer LJ, Leander K, Lemaitre RN, Lewis CE, Liang J; Lifelines Cohort Study, Liu J, Mägi R, Manichaikul A, Meitinger T, Metspalu A, Milaneschi Y, Mohlke KL, Mosley TH Jr, Murray AD, Nalls MA, Nang EK, Nelson CP, Nona S, Norris JM, Nwuba CV, O’Connell J, Palmer ND, Papanicolau GJ, Pazoki R, Pedersen NL, Peters A, Peyser PA, Polasek O, Porteous DJ, Poveda A, Raitakari OT, Rich SS, Risch N, Robinson JG, Rose LM, Rudan I, Schreiner PJ, Scott RA, Sidney SS, Sims M, Smith JA, Snieder H, Sofer T, Starr JM, Sternfeld B, Strauch K, Tang H, Taylor KD, Tsai MY, Tuomilehto J, Uitterlinden AG, van der Ende MY, van Heemst D, Voortman T, Waldenberger M, Wennberg P, Wilson G, Xiang YB, Yao J, Yu C, Yuan JM, Zhao W, Zonderman AB, Becker DM, Boehnke M, Bowden DW, de Faire U, Deary IJ, Elliott P, Esko T, Freedman BI, Froguel P, Gasparini P, Gieger C, Kato N, Laakso M, Lakka TA, Lehtimäki T, Magnusson PKE, Oldehinkel AJ, Penninx BWJH, Samani NJ, Shu XO, van der Harst P, Van Vliet-Ostaptchouk JV, Vollenweider P, Wagenknecht LE, Wang YX, Wareham NJ, Weir DR, Wu T, Zheng W, Zhu X, Evans MK, Franks PW, Gudnason V, Hayward C, Horta BL, Kelly TN, Liu Y, North KE, Pereira AC, Ridker PM, Tai ES, van Dam RM, Fox ER, Kardia SLR, Liu CT, Mook-Kanamori DO, Province MA, Redline S, van Duijn CM, Rotter JI, Kooperberg CB, Gauderman WJ, Psaty BM, Rice K, Munroe PB, Fornage M, Cupples LA, Rotimi CN, Morrison AC, Rao DC, Loos RJF.
Nat Commun. 2019 Jan 22;10(1):376. doi: 10.1038/s41467-018-08008-w.
PMID: 30670697

 

A Statistical Method for Joint Estimation of Cis-eQTLs and Parent-of-Origin Effects under Family Trio Design.
Zhabotynsky V, Inoue K, Magnuson T, Calabrese JM, Sun W.
Biometrics. 2019 Jan 22. doi: 10.1111/biom.13026. [Epub ahead of print]
PMID: 30666629

 

Single-cell transcriptomic analysis of mouse neocortical development.
Loo L, Simon JM, Xing L, McCoy ES, Niehaus JK, Guo J, Anton ES, Zylka MJ.
Nat Commun. 2019 Jan 11;10(1):134. doi: 10.1038/s41467-018-08079-9.
PMID: 30635555

 

A junction coverage compatibility score to quantify the reliability of transcript abundance estimates and annotation catalogs.
Soneson C, Love MI, Patro R, Hussain S, Malhotra D, Robinson MD.
Life Sci Alliance. 2019 Jan 17;2(1). pii: e201800175. doi: 10.26508/lsa.201800175. Print 2019 Feb.
PMID: 30655364

 

Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs.
Yimit A, Adebali O, Sancar A, Jiang Y.
Nat Commun. 2019 Jan 18;10(1):309. doi: 10.1038/s41467-019-08290-2.
PMID: 30659176


Jason Whitmire Awarded R01 from NIAID

January 25, 2019

Jason Whitmire, PhD (Associate Professor, Genetics) is the PI on a new award from NIAID.

The project, titled “Regulation of CD8+ T cell responses to chronic virus infection” starts in February and represents the second R01 that Jason has secured recently.  The project is focused on understanding why CD8+ T cells undergo excessive apoptosis or become functionally inactive and unable to resolve infection during chronic viral infections in mice and humans.  Jason’s lab recently identified a critical link between CD8+ T cell expression of UTX, an H3K27 demethylase, and impaired CD8+ T cell responses to chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Virus-specific CD8+ T cells lacking UTX showed improved accumulation and maintenance over time, reduced expression of the inhibitory receptors, and were resistant to apoptosis. Data suggest that UTX restricts virus-specific CD8+ T cell responses by increasing T cell expression of inhibitory receptors, perhaps converting cells with memory potential into functionally exhausted or senescent cells.

The central hypothesis is that UTX controls T cell differentiation through a mixture of demethylase-dependent and demethylase-independent mechanisms that promote gene expression, including at inhibitory receptor loci.  Information learned from this project will be useful for comprehending how epigenetic changes due to histone methylation guide CD8+ T cell exhaustion. Long-term, the research may implicate the use of pharmacologic inhibitors of UTX to improve CD8+ T cell-mediated immune defenses.



Systems Genetics Core Facility Seeks New Director

January 23, 2019

Established in 2012, the SGCF is the home of the Collaborative Cross (CC) murine Genetic Reference Panel. It is one of the cores of the UNC School of Medicine and is managed by the Department of Genetics.

The SGCF directly supports the research interests within the UNC community to develop new and improved animal models of human disease and to facilitate systems genetics approaches to biomedical traits.  The SGCF has two main tasks: 1) Maintenance and distribution of CC mouse inbred strains and its derivatives to researchers at UNC and around the world; and 2) Curation and distribution of genetic information from these CC inbred strains.

The director position will be at the Assistant Professor level (fixed-term).  The successful candidate will lead a dedicated team in a dynamic environment to execute diverse aspects of the core within allotted resources and in coordination with the scientific direction of the Department of Genetics. The director will interface with customers to design and execute their orders; and will be responsible for the financial and regulatory oversight of the SGCF. The director will have the opportunity to dedicate part of his/her effort to independent research programs within the Department of Genetics.

Interested individuals should apply for this position online at:http://unc.peopleadmin.com/postings/153881 and include a curriculum vitae and cover letter.  Please include names and addresses of four references. Women and individuals identifying as underrepresented are strongly encouraged to apply.



Jason Stein and Michael Love Awarded R01 from NIH

January 16, 2019

Jason Stein, PhD (Assistant Professor, Genetics and Neuroscience Center) and Michael Love, Dr. Rer. Nat. (Assistant Professor, Biostatistics and Genetics) are co-PIs on a new R01 award from NIH titled “pathQTL: Integrative Multi-Omics Causal Inference of Molecular Mechanisms Leading to Neuropsychiatric Illness”.  The goal of the project is to develop and experimentally validate a statistical tool, called pathQTL, to predict the causal molecular and brain structural paths by which a genetic variant creates risk for neuropsychiatric disorder through the integration of multi-omic QTL datasets.

 

Recruitment for postdoctoral fellows to focus on this project is underway.  Interested candidates are welcome to contact Drs. Stein or Love directly to discuss these opportunities.

 



Genetics, BCB and GMB Faculty Recognized for Mentoring Excellence

January 14, 2019

The Office of Graduate Education and the Office of Faculty Affairs and Leadership Development is recognizing ten outstanding faculty for Excellence in Basic Science Mentoring.  Five of the awardees have appointments in Genetics or serve as faculty for either Bioinformatics and Computational Biology (BCB) or Genetics and Molecular Biology (GMB), curricula managed by the department.  Congratulations to Kathleen Caron (Genetics, GMB), Henrik Dohlman (BCB), Ben Major (BCB), Jeff Sekelsky (Genetics, GMB) and Brian Strahl (BCB, GMB).  The awards will be presented on Tuesday, January 15th at 2pm in 1131 Bioinformatics.



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