Department of Genetics Newsletter - Fall 2008

Congratulations

Kirk Wihelmsen has received an appointment to an endowed professorship. He has been named a Carol Masters Schiller Scholar in Neurology.

Kathleen Caron has been asked to represent the basic sciences research of the Pregnancy & Perinatology Branch at the NICHD Advisory Council Meeting on Sept. 11th. Advisory Councils consist of scientists as well as non-scientists who make decisions on future research goals and directions of an Institute. The goal of her presentation will be to showcase for Council some of the successes that result from funding of basic science through the P&P Branch of NICHD.    An important element of the presentation will also include recommendations for future research directions for the field as a whole. The title of her presentation is "Adrenomedullin Dosage at the Maternal-Fetal Interface: A Tale of Two Sides."

New Grants

• Ned Sharpless has received a University Cancer Research Fund Innovation Award for studies on "Pharmacological Quiescence to Reduce Therapy-Associated Myelosuppression."
• Bev Koller received a new R01 grant award from NIH (National Heart, Lung and Blood Institute) on "Characterization of Asthma Associated Polymorphisms" and a new R21 grant from the National Institute of Mental Health on "Functionally Significant Polymorphisms in Serotonin Pathway Genes."
• Frank Conlon received a new R01 from NIH (National Heart, Lung and Blood Institute) on "TBX5 and Cardiac Proliferation."

Dr. Aravind Asokan is joining the Department as an Assistant Professor. He earned his Ph.D. in Pharmaceutical Chemistry at UNC at Chapel Hill in 2004 and has done postdoctoral work with Dr. Jude Samulski in the Gene Therapy Center. His research interests range from mapping AAV-receptor interactions to directed evolution of AAV vectors and intestinal gene delivery. He is also collaborating with investigators in the Divisions of Gastroenterology and Pulmonary Medicine in the Department of Medicine as part of a major commitment to the design of new genetic mucosal vaccines. His laboratory is located in the Gene Therapy Center in the Thurston-Bowles Building.

Dr. Daniel Pomp is transferring his primary appointment as Professor from the Department of Nutrition in the School of Public Health to the Department of Genetics. He will maintain joint appointments in Nutrition and in the Department of Cell and Molecular Physiology. He has been actively collaborating with faculty in Genetics since he came to UNC in 2005. He has a Ph.D. in Animal Genetics from NC State, carried out postdoctoral work at the University of California at Davis, and has held faculty positions at Oklahoma State University and the University of Nebraska. He is a national and international leader in the field of mammalian quantitative genetics. His is particularly involved in the identification of genes involved in obesity and in behavioral traits, such as aggression, using the mouse as a model system. He will move his lab into the Genetic Medicine Building when it opens.

New Guidelines

Terry Magnuson continues to serve on the National Academies stem cell committee that authored voluntary guidelines for human embryonic stem cells research in 2005. The committee released a second version of amendments to the guidelines on September 5, 2008. These amendments address issues surrounding the new induced pluripotent stem cells as well as other issues on egg donation. The guidelines along with the 2007 and 2008 amendments can be obtained at http://dels.nas.edu/bls/stemcells/.

Jessica Nadler, Terry Magnuson, and colleagues analyze mouse behavioral phenotypes associated with autism

Jessica Nadler in Terry Magnuson's lab and collaborators in the UNC Neurodevelopmental Disorders Research Center have been characterizing mouse phenotypes that correlate with characteristics of autism in human patients. Their recent studies add seven strains, including one wild-derived strain (PERA/EiJ), for a total of seventeen inbred strains that have been phenotyped for sociability, preference for social novelty, and resistance to changes in a learned pattern of behavior, among other traits. One strain, C58/J, had a particularly interesting phenotype, including low social preference, poor performance in a T-maze, and overt motoric stereotypy. These behavioral differences are being correlated with large-scale gene expression differences across brain regions in the various strains with the ultimate goal of identifying genes involved in autism.

Moy SS, Nadler JJ, Young NB, Nonneman RJ, Segall SK, Andrade GM, Crawley JN, Magnuson TR. Social approach and repetitive behavior in eleven inbred mouse strains. Behav Brain Res 191, 118-29 (2008).

Terry Van Dyke's lab shows that inactivation of the Gadd45a DNA damage response gene leads to greater sensitivity to ionizing radiation

Lu X, Yang C, Hill R, Yin C, Hollander MC, Fornace AJ Jr, Van Dyke T. Inactivation of gadd45a sensitizes epithelial cancer cells to ionizing radiation in vivo resulting in prolonged survival. Cancer Res 68, 3579-83 (2008).

The Genetics Dept. is growing and changing with many new graduate students and postdoctoral fellows joining the department, as well as many graduate students and postdocs/fellows finishing their education/training and moving on to the next level. We would like to welcome the newcomers and acknowledge some of the accomplishments.

Postdoctoral fellows who have joined Genetics labs: 

Terry Magnuson’s lab

• Josh Mugford, Ph.D., Harvard
• Mauro Calabrese, Ph.D., MIT

Karen Mohlke’s lab

David Threadgill’s lab

• David Bautz, Ph.D., UNC-CH (dissertation research with Dr. Alex Tropsha, Biochemistry and Biophysics)

Graduate Students who have joined Genetics labs include: 

Frank Conlon’s lab

• Erin Kaltenbrun
• Kerry Dehghanpisheh

Karen Mohlke’s lab

• Damien Croteau-Chonka (Genetics and Molecular Biology Curriculum and the Bioinformatics & Computational Biology training program)

Research Staff joining the department include:

Aravind Asokan’s lab

Frank Conlon’s lab

• Lauren Kuchenbrod has joined the lab as a Research Technician.

Congratulations to Genetics Department trainees awarded honors/prizes

Research faculty:

• Jessica Nadler (Research Assistant Professor) from Terry Magnuson’s lab is currently on leave to complete an AAAS Health Policy fellowship in Washington, DC.

Graduate students:

• Kathleen Christine (Department of Biology student in Frank Conlon's lab) received an American Heart Association (AHA) Pre-doctoral Fellowship, as well as a UNC Lineberger Graduate Fellow Award.

Congratulations also to former Genetics department members

• Magnuson Lab postdoc Courtney Griffin has been appointed as Assistant Professor at the Oklahoma Medical Research Foundation. She will continue pursuing her work on chromatin remodeling and vascular development.

Graduate Students who recently defended:

Mark Heise's lab:

• Reed Shabman (defense date June 2007) will be a postdoc with Chris Basler at Mount Sinai School of Medicine in NY.

David Threadgill’s lab:

• Tang-Cheng Lee will be starting a postdoc at Baylor College of Medicine in Houston.
• Ming Yu will be starting a postdoc at the Fred Hutchinson Cancer Center In Seattle.

Recent Publications Featuring Undergraduates, Graduate Students and Postdoctoral Trainees: 

Shawn Ahmed’s lab:

• Mia Lowden, Teresa Lee, Bettina Meier, Julie Hall and Shawn Ahmed. End-joining at Caenorhabditis elegans telomeres. Genetics, in press.
• Sebastien Greiss, Julie Hall, Shawn Ahmed and Anton Gartner. C. elegans SIR-2.1 translocation is linked to a pro-apoptotic pathway parallel to cep-1/p53 during DNA damage induced apoptosis. Genes and Development, in press.

Debbie Threadgill’s lab:

• MJ LaGier and DS Threadgill (2008). Identification of novel genes in the oral pathogen Campylobacter rectus. Oral Microbiology and Immunology 23:406-412.

For more information about current graduate students and postdoctoral fellows in Genetics Dept. Labs, please visit individual researcher’s web pages. If you would like to see news from your lab here, please contact Debbie Threadgill (Deborah_Threadgill@med.unc.edu).

We just returned from our 7^th annual retreat, which was held at Atlantic Beach this year. The retreat brings together geneticists across campus. Attendance was at 175, the science was outstanding and everyone had a good time. The retreat represents a time where we all learn about other projects across a diversity of systems and approaches. Hopefully new friendships and new collaborations were established. Next years retreat will be held in Asheville from September 25 to September 27, so mark your calendars. The Department is scheduled to move into the new Genetic Medicine building in December of this year. We will be located on the top floor with great views. The building is beautifully designed to maximize the lab work. A space plan for the floor has been established and we are beginning to work with individual labs on planning for the transition. With the addition of new space, we will be recruiting new faculty in the areas of stem cell biology, cancer and computational genetics/genomics. We will also be focusing on a plan for human genetics. I am pleased to announce that Will Valdar will be joining us in September 2009 as a new Assistant Professor. He currently is a postdoc at the Wellcome Trust Centre for Human Genetics in Oxford. His focus is bioinformatics and statistical genetics. It is with mixed feelings also to announce that David and Debbie Threadgill will be leaving us for positions at NC State. David will be assuming the Chair of Genetics and Debbie will be appointed to a tenure track position in Microbiology. As founding members of our department, we will miss them but are excited for them in their new positions. David will keep a faculty appointment with us and will continue to be closely integrated with the systems genetics program. One of our big achievements last year was the establishment of the next generation sequencing facility with support from the UCRF. We were able to recruit Piotr Mieczkowski as director of the facility. Piotr also holds a faculty appointment in Genetics and he brings a wealth of experience in high throughput genomics technology. Finally, we also welcome Virginia Miller as a new member of the Genetics department and as Assistant Dean for Graduate Education. Virginia is an international leader in bacterial pathogenesis. We will have a chance to get to know Piotr and Virginia at the Wednesday noon research colloquium, which begins this week. Based on feedback from faculty, postdocs and students, we will be having two 30 minute postdoc/student talks per week with occasional outside speakers and faculty promotion talks. I look forward to seeing everyone there.

Recent Publications

• Asokan A, Johnson JS, Li C, Samulski RJ. Bioluminescent virion shells: new tools for quantitation of AAV vector dynamics in cells and live animals. Gene Ther (2008) Jul 31 [Epub ahead of print].
• DiPrimio N, Asokan A, Govindasamy L, Agbandje-McKenna M, Samulski RJ. Surface loop dynamics in adeno-associated virus capsid assembly. J Virol 82, 5178-89 (2008).
• Li C, Hirsch M, Carter P, Asokan A, Zhou X, Wu Z, Samulski RJ. A small regulatory element from chromosome 19 enhances liver-specific gene expression. Gene Ther (2008) Aug 14 [Epub ahead of print].
• Li W, Asokan A, Wu Z, Van Dyke T, DiPrimio N, Johnson JS, Govindaswamy L, Agbandje-McKenna M, Leichtle S, Redmond DE Jr, McCown TJ, Petermann KB, Sharpless NE, Samulski RJ. Engineering and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Mol Ther 16, 1252-60 (2008).

• Stamm DS, Aylsworth AS, Stajich JM, Kahler SG, Thorne LB, Speer MC, Powell CM. Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. Am J Med Genet A 146A, 1832-41 (2008).

• Susswein LR, Skrzynia C, Lange LA, Booker JK, Graham ML 3rd, Evans JP. Increased uptake of BRCA1/2 genetic testing among African American women with a recent diagnosis of breast cancer. J Clin Oncol 26, 32-6 (2008).

• Frieman M, Heise M, Baric R. SARS coronavirus and innate immunity. Virus Res 133, 101-12 (2008).
• Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG, Accavitti-Loper MA, Madden VJ, Sun L, Ye Z, Lich JD, Heise MT, Chen Z, Ting JP. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451, 573-7 (2008).
• Morrison TE, Heise MT. The host complement system and arbovirus pathogenesis. Curr Drug Targets 9, 165-72 (2008).

• Duncan GE, Inada K, Farrington JS, Koller BH. Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction. Brain Res 1221, 41-8 (2008).
• Moy SS, Nadler JJ, Poe MD, Nonneman RJ, Young NB, Koller BH, Crawley JN, Duncan GE, Bodfish JW. Development of a mouse test for repetitive, restricted behaviors: relevance to autism. Behav Brain Res 188, 178-94 (2008).

• Lange LA, Reiner AP, Carty CL, Jenny NS, Cushman M, Lange EM.  Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults. J Thromb Haemost 6, 654-9 (2008).

• Lange LA, Reiner AP, Carty CL, Jenny NS, Cushman M, Lange EM.  Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults. J Thromb Haemost 6, 654-9 (2008).
• Caudle AS, Kim HJ, Tepper JE, O'Neil BH, Lange LA, Goldberg RM, Bernard SA, Calvo BF, Meyers MO. Diabetes mellitus affects response to neoadjuvant chemoradiotherapy in the management of rectal cancer. Ann Surg Oncol 15, 1931-6 (2008).
• Marvelle AF, Lange LA, Qin L, Adair LS, Mohlke KL. Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort. Diabetes 57, 1987-91 (2008).
• Susswein LR, Skrzynia C, Lange LA, Booker JK, Graham ML 3rd, Evans JP. Increased uptake of BRCA1/2 genetic testing among African American women with a recent diagnosis of breast cancer. J Clin Oncol 26, 32-6 (2008).

• Chamberlain SJ, Yee D, Magnuson T. Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency. Stem Cells 26, 1496-505 (2008).
• Moy SS, Nadler JJ, Young NB, Nonneman RJ, Segall SK, Andrade GM, Crawley JN, Magnuson TR. Social approach and repetitive behavior in eleven inbred mouse strains. Behav Brain Res 191, 118-29 (2008).

• Passman JN, Dong XR, Wu SP, Maguire CT, Hogan KA, Bautch VL, Majesky MW. A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells. Proc Natl Acad Sci U S A 105, 9349-54 (2008).

• Marvelle AF, Lange LA, Qin L, Adair LS, Mohlke KL. Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort. Diabetes 57, 1987-91 (2008).
• Gaulton KJ, Willer CJ, Li Y, Scott LJ, Conneely KN, Jackson AU, Duren WL, Chines PS, Narisu N, Bonnycastle LL, Luo J, Tong M, Sprau AG, Pugh EW, Doheny KF, Valle TT, Abecasis GR, Tuomilehto J, Bergman RN, Collins FS, Boehnke M, Mohlke KL. Comprehensive Association Study of Type 2 Diabetes and Related Quantitative Traits with 222 Candidate Genes. Diabetes (2008).

• Muenzer J, Martins AM. Hunter syndrome: to treat or not to treat. Acta Paediatr Suppl 97, 55-6 (2008).

• Bhati R, Patterson C, Livasy CA, Fan C, Ketelsen D, Hu Z, Reynolds E, Tanner C, Moore DT, Gabrielli F, Perou CM, Klauber-DeMore N. Molecular characterization of human breast tumor vascular cells. Am J Pathol 172, 1381-90 (2008).
• Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, Smith LV, Labbok MH, Geradts J, Bensen JT, Jackson S, Nyante S, Livasy C, Carey L, Earp HS, Perou CM. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 109, 123-39 (2008).

• Gordon RR, Hunter KW, La Merrill M, Sørensen P, Threadgill DW, Pomp D. Genotype x diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis. Mamm Genome 19, 179-89 (2008).
• Gordon RR, Hunter KW, Sørensen P, Pomp D. Genotype x diet interactions in mice predisposed to mammary cancer. I. Body weight and fat. Mamm Genome 19, 163-78 (2008).
• Hartmann J, Garland T Jr, Hannon RM, Kelly SA, Muñoz G, Pomp D. Fine Mapping of "Mini-Muscle," a Recessive Mutation Causing Reduced Hindlimb Muscle Mass in Mice. J Hered (2008) Jun 9 [Epub ahead of print].
• Leamy LJ, Pomp D, Lightfoot JT. An Epistatic Genetic Basis for Physical Activity Traits in Mice. J Hered (2008) Jun 5 [Epub ahead of print].
• Lightfoot JT, Turner MJ, Pomp D, Kleeberger SR, Leamy LJ. Quantitative trait loci for physical activity traits in mice. Physiol Genomics 32, 401-8 (2008).
• Pomp D, Nehrenberg D, Estrada-Smith D. Complex genetics of obesity in mouse models. Annu Rev Nutr 28, 331-45 (2008).

• Stamm DS, Aylsworth AS, Stajich JM, Kahler SG, Thorne LB, Speer MC, Powell CM. Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. Am J Med Genet A 146A, 1832-41 (2008).

• Amin C, Wallen E, Pruthi RS, Calvo BF, Godley PA, Rathmell WK. Preoperative Tyrosine Kinase Inhibition as an Adjunct to Debulking Nephrectomy. Urology (2008).
• Rathmell WK, Chen S. VHL inactivation in renal cell carcinoma: implications for diagnosis, prognosis and treatment. Expert Rev Anticancer Ther 8, 63-73 (2008).
• Rathmell WK, Monk JP. High-Dose-Intensity MVAC for Advanced Renal Medullary Carcinoma: Report of Three Cases and Literature Review. Urology (2008).

• Kim WY, Sharpless NE. VHL inactivation: a new road to senescence. Cancer Cell 13, 295-7 (2008).
• Li W, Asokan A, Wu Z, Van Dyke T, DiPrimio N, Johnson JS, Govindaswamy L, Agbandje-McKenna M, Leichtle S, Redmond DE Jr, McCown TJ, Petermann KB, Sharpless NE, Samulski RJ. Engineering and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Mol Ther 16, 1252-60 (2008).
• Min JN, Whaley RA, Sharpless NE, Lockyer P, Portbury AL, Patterson C. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol 28, 4018-25 (2008).
• Shah U, Sharpless NE, Hayes DN. LKB1 and lung cancer: more than the usual suspects. Cancer Res 68, 3562-5 (2008).

• Bulik CM, Von Holle A, Siega-Riz AM, Torgersen L, Lie KK, Hamer RM, Berg CK, Sullivan P, Reichborn-Kjennerud T. Birth outcomes in women with eating disorders in the Norwegian Mother and Child cohort study (MoBa). Int J Eat Disord (2008) Aug 21 [Epub ahead of print].
• Furberg H, Lichtenstein P, Pedersen NL, Bulik CM, Lerman C, Sullivan PF. Snus use and other correlates of smoking cessation in the Swedish Twin Registry. Psychol Med 38, 1299-308 (2008).
• Konneker T, Barnes T, Furberg H, Losh M, Bulik CM, Sullivan PF. A searchable database of genetic evidence for psychiatric disorders. Am J Med Genet B Neuropsychiatr Genet  147B, 671 (2008).
• Losh M, Sullivan PF, Trembath D, Piven J. Current Developments in the Genetics of Autism: From Phenome to Genome. J Neuropathol Exp Neurol 67, 829 (2008).
• Webb BT, Sullivan PF, Skelly T, van den Oord EJ. Model-based gene selection shows engrailed 1 is associated with antipsychotic response. Pharmacogenet Genomics 18, 751-759 (2008).

• Sun W, Yuan S, Li KC. Trait-trait dynamic interaction: 2D-trait eQTL mapping for genetic variation study. BMC Genomics 9, 242 (2008).

• MJ LaGier and DS Threadgill, Identification of novel genes in the oral pathogen Campylobacter rectus. Oral Microbiology and Immunology 23,406 (2008).

• Gordon RR, Hunter KW, La Merrill M, Sørensen P, Threadgill DW, Pomp D. Genotype x diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis. Mamm Genome 19, 179-89 (2008).

• Li W, Asokan A, Wu Z, Van Dyke T, DiPrimio N, Johnson JS, Govindaswamy L, Agbandje-McKenna M, Leichtle S, Redmond DE Jr, McCown TJ, Petermann KB, Sharpless NE, Samulski RJ. Engineering and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Mol Ther 16, 1252-60 (2008).
• Lu X, Yang C, Hill R, Yin C, Hollander MC, Fornace AJ Jr, Van Dyke T. Inactivation of gadd45a sensitizes epithelial cancer cells to ionizing radiation in vivo resulting in prolonged survival. Cancer Res 68, 3579-83 (2008).
• Wu Z, Sun J, Zhang T, Yin C, Yin F, Van Dyke T, Samulski RJ, Monahan PE. Optimization of self-complementary AAV vectors for liver-directed expression results in sustained correction of hemophilia B at low vector dose. Mol Ther 16, 280-9 (2008).

• Ehlers CL, Lind PA, Wilhelmsen KC. Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians. BMC Med Genet 9, 35 (2008).
• Quinzii CM, Vu TH, Min KC, Tanji K, Barral S, Grewal RP, Kattah A, Camaño P, Otaegui D, Kunimatsu T, Blake DM, Wilhelmsen KC, Rowland LP, Hays AP, Bonilla E, Hirano M. X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1. Am J Hum Genet 82, 208-13 (2008).