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Researchers at UCD

Noreen Sheehy

Lecturer

School Of Medicine & Medical Science
CRID
Belfield
Dublin 4

Tel: +353 1 7161255
Email: noreen.sheehy@ucd.ie

Professional

               

Education

Year 1996 Institution: University of Warwick
Qualification: PhD Subject: Virology Drug resistance development in HIV infected individuals
Year 1987 Institution: NUI Galway, IRL
Qualification: BSc Subject:
Year 1989 Institution: NUI Galway, IRL
Qualification: MSc Subject: Biotechnology
         

Publications

 

Book Chapters

Araujo A, Sheehy N, Takahashi H, and Hall WW.; (2002) 'Human Retroviruses : Concomitant Infections with Human Immunodeficiency Virus Type I (HIV-I) and Human T lymphotropic Viruses Type I (HTLV-I) and Type II (HTLV-II)' In: K.A. Bogden and J.M. Guthmuller (eds). Polymicrobial Infections. Washington DC: American Society of Microbiology (ASM) Press Washington DC. [Details]
 

Peer Reviewed Journals

Marban,C;Bukong,TN;Hall,WW; Sheehy,N (2012) 'Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway'. Retrovirology, . [Details]
Gu L, Tsuji T, Jarboui MA, Yeo GP, Sheehy N, Hall WW, Gautier VW; (2011) 'Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import'. Retrovirology, 8 (17). [DOI] [Details]
Watters KM, Dean J, Gautier V, Hall WW, Sheehy N; (2010) 'Tax 1-independent induction of vascular endothelial growth factor in adult T-cell leukemia caused by human T-cell leukemia virus type 1'. Journal of Virology, 84 (10):5222-5228. [Details]
Watters KM, Dean J, Hasegawa H, Sawa H, Hall W, Sheehy N; (2010) 'Cytokine and growth factor expression by HTLV-1 Lck-tax transgenic cells in SCID mice'. AIDS Research and Human Retroviruses, 26 :593-603. [Details]
Gautier, V. W.,Gu, L.,O'Donoghue, N.,Pennington, S.,Sheehy, N.,Hall, W. W.; (2009) 'In vitro nuclear interactome of the HIV-1 Tat protein'. Retrovirology, 6 . Available Online [Details]
Gu L, Dean J, Oliveira AL, Sheehy N, Hall WW, Gautier VW; (2009) 'Expression profile and differential regulation of the Human l-mfa domain-Containing protein (HIC) gene in immune cells'. IMMUNOLOGY LETTERS, 123 (2):179-184. [Details]
Dean J, Hashimoto K, Tsuji T, Gautier V, Hall WW, Sheehy N; (2009) 'Functional interaction of HTLV-1 tax protein with the POZ domain of the transcriptional repressor BCL6'. Oncogene, 28 (42):3723-3734. [Details]
Tsuji T, Sheehy N, Gautier VW, Hayakawa H, Sawa H, Hall WW.; (2007) 'The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent'. Journal of Biological Chemistry, 282 (18):13875-13883. [Details]
Schaffer, K; Sheehy, N; Coughlan, S; Bergin, C; Hall, WW; ; (2006) 'JC virus in the Irish population: Significant increase of genotype 2 in immunocompromised individuals'. Journal of Neurovirology, 12 (1):39-46. [Details]
Sheehy, N; Lillis, L; Watters, K; Lewis, M; Gautier, V; Hall, W; ; (2006) 'Functional analysis of human T lymphotropic virus type 2 Tax proteins'. Retrovirology, 3 (NA). [Details]
Hasegawa, H; Sawa, H; Lewis, MJ; Orba, Y; Sheehy, N; Yamamoto, Y; Ichinohe, T; Tsunetsugu-Yokota, Y; Katano, H; Takahashi, H; Matsuda, J; Sata, T; Kurata, T; Nagashima, K; Hall, WW; ; (2006) 'Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human T-lymphotropic virus type I'. Nature Medicine, 12 (4):466-472. [Details]
Gautier, VW; Sheehy, N; Duffy, M; Hashimoto, K; Hall, WW; ; (2005) 'Direct interaction of the human 1-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity'. Proceedings of the National Academy of Sciences of the United States of America, 102 (45):16362-16367. [Details]
Duffy, M; Salemi, M; Sheehy, N; Vandamme, AM; Hegarty, J; Curry, M; Nolan, N; Kelleher, D; McKiernan, S; Hall, WW; ; (2002) 'Comparative rates of nucleotide sequence variation in the hypervariable region of E1/E2 and the NS5b region of hepatitis C virus in patients with a spectrum of liver disease resulting from a common source of infection'. Virology, 301 (2):354-364. [Details]
Lewis, MJ,Sheehy, N,Salemi, M,VanDamme, AM,Hall, WW; (2002) 'Comparison of CREB- and NF-kappa B-mediated transactivation by human T lymphotropic virus type II (HTLV-II) and type I (HTLV-I) tax proteins'. Virology, 295 :182-189. [DOI] [Details]
Hasegawa, H,Tatsumi, M,Ogawa-Goto, K,Takahashi, H,Kojima, A,Iwasaki, T,Kurata, T,Sata, T,Takeuchi, T,Sheehy, N,Sawa, H,Nagashima, K,Hall, WW; (2002) 'Processing of the HTLV-II envelope precursor glycoprotein gp63 by furin is essential for cell fusion activity'. AIDS, 18 :1253-1260. [Details]
Egan, JF,O'Leary, B,Lewis, MJ,Mulcahy, F,Sheehy, N,Hasegawa, H,Fitzpatrick, F,O'Connor, JJ,O'Riordan, J,Hall, WW; (1999) 'High rate of human T lymphotropic virus type IIa infection in HIV type 1-infected intravenous drug abusers in Ireland'. AIDS Research and Human Retroviruses, 15 :699-705. [Details]
Sheehy, N,Markey, B,Quinn, PJ; (1997) 'Analysis of partial 16S rRNA nucleotide sequences of Chlamydia pecorum and C-psittaci'. Fems Immunology and Medical Microbiology, 17 :201-205. [Details]
Markey, B; Bassett, H; Sheehy, N; Gleeson, M; Clements, L; ; (1996) 'Chlamydial abortion in an Irish sheep flock'. Irish Veterinary Journal, 49 (5). [Details]
Markey B., Bassett H., Sheehy N., Gleeson M. and Clements L.; (1996) 'Chlamydial abortion in an Irish sheep flock'. Irish Veterinary Journal, 49 :290-293. [Details]
Sheehy, N; Markey, B; Gleeson, M; Quinn, PJ; ; (1996) 'Differentiation of Chlamydia psittaci and C-pecorum strains by species-specific PCR'. Journal of Clinical Microbiology, 34 (12):3175-3179. [Details]
Sheehy, N,Markey, B,Gleeson, M,Quinn, PJ; (1996) 'Differentiation of Chlamydia psittaci and C-pecorum strains by species-specific PCR'. Journal of Clinical Microbiology, 34 :3175-3179. [Details]
Sheehy N, Desselberger U, Whitwell H, Ball JK. (1996) 'Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 during zidovudine (AZT) therapy'. Journal of General Virology, 77 :1071-1081. [Details]
Markey, B,Bassett, H,Sheehy, N,Gleeson, M,Clements, L; (1996) 'Chlamydial abortion in an Irish sheep flock'. VET J, 49 . [Details]
Sheehy N., Markey B., Gleeson M., and Quinn P.J.; (1996) 'Differentiation of Chlamydia psittaci and Chlamydia pecorum strains by species-specific PCR'. Journal of Clinical Microbiology, 34 :3175-3179. [Details]
Sheehy N, Desselberger U. (1993) 'Sequence analysis of reverse transcriptase genes of zidovudine (AZT)-resistant and -sensitive human immunodeficiency virus type 1 strains'. Journal of General Virology, 74 (2):223-228. [Details]
 

Conference Publications

Céline Marban, William W Hall, Noreen Sheehy (2011) Regulation of AP-1 activity by the HTLV-2 APH-2 protein 15TH International Conference on Human Retrovirology HTLV and Related Viruses [Details]
Áine McCabe, William W Hall, Noreen Sheehy (2011) Physical and functional interaction between the HTLV-1 Tax oncoprotein and the cellular LIM domain protein FHL3 15TH International Conference on Human Retrovirology HTLV and Related Viruses Leuven and Gembloux, Belgium, [Details]
Yukiko Miyatake, Utano Tomaru, André L A Oliveira, Noreen Sheehy, Takashi Yoshiki, Masanori Kasahara, William W Hall (2011) Stromal cells help ATL cells to escape from apoptosis induced by histone deacetylase inhibitors 15th International Conference on Human Retrovirology HTLV and related Retroviruses Leuven and Gembloux, Belgium, , 04-JUN-11 - 08-JUN-11 [Details]
Tsuji T, Sheehy N, Gautier VW, Hayakawa H, Sawa H, Hall WW (2007) The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent 13th International Conference on Human Retrovirology HTLV Meeting [Details]
L Gu, VW Gautier, N Sheehy, T Tsuji, H Hayakawa, WW Hall (2006) The human I-mfa domain containing protein, HIC, interacts with HIV-1 Tat and Rev and sequesters them in the cytoplasm International Meeting of The Institute of Human Virology [Details]
Hasegawa H,Sawa H, Lewis M, Orba Y, Sata T, Kurata T, Nagashima K, Sheehy N, Hall WW. (2005) Development of a model of Adult T cell Leukemia/Lymphoma 12th International Conference on Human Retrovirology Montego Bay Jamaica, [Details]
Sheehy N, Garry A, Lillis L, Watters K, Gautier V, Duffy M, Lewis M, Hall WW. (2005) Functional analysis of Human T cell leukemia virus type IIa Tax proteins 12th International Conference on Human Retrovirology Montego Bay Jamaica, [Details]
Tsuji T, Sheehy N, , Hayakawa H, Gautier VW, Sawa H, Hall WW. (2005) Subcellular localization of HTLV-1 Tax using GFP-tagged proteins 12th International Conference on Human Retrovirology Montego Bay, Jamaica, [Details]
Watters KM, Hayakawa H, Gautier v, Dean J, Roe B, Waters A, Hall WW, Sheehy N. (2005) The repression of the VEGF promoter by the HTLV-1 Tax protein 12th International Conference on Human Retrovirology Montego Bay, Jamaica, [Details]
Sheehy N, Hayakawa H, Gautier V, Duffy M, Hall WW. (2003) Direct Interaction of HTLV-2B Tax protein and the tumor suppressor protein VHL negatively regulates viral gene expression 11th International Conference on Human Retroviruses San Francisco, California, [Details]
                                                                                         

Research

Research Interests

My research area is Molecular Virology and specifically relates to the investigation of the pathogenesis of the human retroviruses human T cell leukemia viruses types 1 and 2  (HTLV-1 and HTLV-2, respectively). HTLV-1 causes adult T cell leukemia/lymphoma (ATLL) and chronic inflammatory disorders while HTLV-2 infection is not linked with specific virus related diseases. One key question that still remains unanswered despite intensive research in this area over the past 35 years is why HTLV-1 gives rise to disease while its closely related counter part HTLV-2 is not clearly associated with cancer development. The identification and characterization of key virus/host interactions that contribute to ATLL in individuals infected with HTLV-1 but not HTLV-2 has been the focus of much my HTLV research to date. The overall goal of such work is not only to provide insights into the different clinical outcomes of HTLV infections but also to identify and characterize key cellular players in ATLL development, which is of great interest to those hoping to develop novel cancer therapeutics.

Specific research interests 

1.  Regulation of cellular signalling pathways by HTLV Tax oncogenic proteins

2. Investigation of the pathogenesis of leukemia/lymphoma development in ATLL mouse animal model

3. Characterization of novel HTLV /cellular protein/protein interactions

Using a combination of mutational studies and viral /cellular promoter assays we have extensively characterized the role of HTLV Tax oncogenic proteins in the deregulation of cellular signalling pathways. The findings from these studies may in the future help in the development of innovative therapies that specifically target such signalling pathways. Our host/viral protein protein interaction and functional studies have shown that HTLV proteins disrupt the normal function of a multitude of cellular proteins many of which are involved in cell survival and proliferation. These studies have highlighted the fact that many of the cellular proteins disrupted by HTLV proteins are also de regulated in non-viral clinical diseases. Our studies, in the context of HTLV, provide important insights into the molecular mechanisms behind the normal cellular function of these proteins and how their abnormal or de-regulated expression may lead to disease. A collaborative study between our lab and the National Institute of Infectious diseases, Tokyo led to the development of models of ATLL in both transgenic and SCID mice that closely resembles disease seen in humans. The development of such models is critical to studies seeking to investigate the molecular mechanism involved in cell transformation and ATLL development. The rapid development of disease in the SCID model (one month) makes this system ideal for the evaluation of a range of therapeutics that may lead to more effective treatments for highly invasive cancer cells.  We have been able to identify key cytokines and adhesion molecules that contribute to the high levels of organ infiltration by leukemic cells in the SCID ATL model. More extensive molecular characterization of the molecular events underlying these events is planned in the future with the hope of identifying therapeutic targets.

Anti sense transcription of the HTLV-1 and HTLV-2 genomes has recently been described and results in the expression of the viral proteins HBZ and APH-2 proteins, respectively. These proteins are speculated to play key roles in the different pathologies observed in HTLV-1 and -2 infected individuals as they, for the most part, represent the only viral proteins to be expressed in infected individuals. We have recently identified panels of cellular interactors for HBZ and APH-2 using the yeast two hybrid system. Many of these proteins function as antiviral restriction factors, immune modulators and transcriptional regulators. We hope to characterize these interactions in the future and determine how they impact on viral replication and the characteristics of T cells. Overall these studies should provide a more extensive picture of the molecular mechanisms that govern the complicated pathogenesis of HTLV-1 and HTLV-2 infection.

 

 

Recent Postgraduates

Karen Watters 2004-2008. PhD Thesis "Investigation of the effect of HTLV Tax1 protein on VEGF expression, and the interaction of Tax1 and PFD3" Principal Supervisor

Ann Marie McCartin 2011-2012 MSc Thesis " "Development of diagnostic methodologies and molecular epidemiology of dengue virus in Vietnam" Principal Supervisor

Meadbh Collis
on 2011-2012 MSc thesis " Evaluation of clinical utility of host typing in liver transplant recipients and treatment relapsers chronically infected with hepatitis C virus" Principal Supervisor

Naomi Hall 2011-2012 MSc thesis  "Development of serological and Molecular Diagnostics for arboviruses"  Principal Supervisor

Brian Gaffney 2011-2012 MSc thesis  "Role of TRIM28 in the pathogenesis of HTLV-2" Principal Supervisor

Current Postgraduate Students

Aine Mc Cabe, Doctor of Philosophy (PhD)   -   Thesis Supervisor
Jane Murphy, Doctor of Philosophy (PhD)   -   Thesis Supervisor

Teaching

Teaching Philosophy

My teaching philosophy is based on the belief that the role of a teacher is that of facilitator that creates the opportunities or environment for student self directed learning in their quest for knowledge.

Modules Coordinated

201200   MEMI30010     Medical Microbiology: Medical Microbiology
201200   MEMI40010     Medical Microbiology: Host-Pathogen Interactions

Enhancement of Teaching

I believe that learning is facilitated by active student participation in the learning process. I am in favor in particular of a social constructivist approach to learning in which learning is considered an active self directed social process in which individuals actively construct knowledge. Because of this, I design my lectures such that I incorporate as many case studies and lab practicals as possible to foster not only the acquisition of knowledge by students but also the development of other desirable attributes such as communication skills, problem solving, critical evaluation of data. Evidence that this method of teaching improves the quality of student learning comes from my observations that students are very willing to contribute in class discussions and prepare relevant material in advance. I believe that hands on practical experience and the application of theory in a practical setting improves overall student learning. The relative importance I place on the benefit of practical lab experience in student learning is reflected in the fact that 30% of the final module result goes for practicals. Analysis of the online UCD student feedback information on the modules I coordinate shows an average satisfaction rating of 3.7 over the past two years. Even though this gives a broad indication of how the students rate these modules I feel the introduction of a tailored mid semester student feedback survey that specifically relates to my modules could provide additional information that could improve student learning

Review and Enhancement of Curriculum

Good module design requires alignment of learning outcomes, assessment and learning/teaching environment/activities (www.ucd.ie/teaching). Currently, I co ordinate two modules MEMI30010 (Stage 3) and MEMI40010 (Stage 4) in the SMMS. MEMI30010 Medical Microbiology module is offered to students with no prior learning of the subject while MEMI40010 is offered to students who have completed MEMI30010. The learning outcomes for MEMI30010 reflect the fact that I want students to learn about a broad range of medically relevant viruses and bacteria in the hope of this will stimulate their interest in and curiosity about the subject. I have designed the module such that it incorporates a variety of teaching/learning activities including formal lectures, case studies and practicals. Learning outcomes and activities are reflected in the assessment methods and weighting of assessment types. These consist of multiple choice exam mid semester (10% final grade), practical exams (30% final grade) and final written exam (60% final grade). The MEMI40010 Host pathogen Interactions module builds on MEMI30010 and has been designed such that students are expected to expand their knowledge of a small number of key medically important infectious agents. In this case students are provided with reviews which they are expected to use as material for self directed learning. This is supported by discussion/tutorial type lectures on each topic provided by people who actively work on these infectious agents. which provides students with the most up to date information on these topics. The provision of practicals, case studies as course material and group discussion on published papers in the modules I co ordinate not only facilitates the acquisition of knowledge but also several other desirable attributes such as problem solving, self directed learning, communication and critique skills.

Developing as a Teacher

In order to improve my knowledge and skills as a university teacher I have completed the following workshops and courses provided by the UCD Centre for Teaching and Learning: The Reflective Practitioner Spring 2008 Small Group Teaching Spring 2008 Educational Technology Spring 2008 Active Learning Spring 2008 Gathering Student Feedback Spring 2008 I was awarded the Graduate Certificate in University Teaching and Learning (Level 9; 30 credits) consisting of two 15 credit modules "Designing and Developing Curricula for Higher Education" "Problem Based Learning in Higher Education" These courses provided me with an understanding of different approaches to teaching and in particular enlightened me about different aspects of student learning. I have been able to apply and incorporate so much of what I studied in the Grad Certificate to the modules I co ordinate. For instance I have tried to introduce a of PBL and tradiam in favor of PBL but am noI have now introduced and encouraged other contributors to MEMI30010 to introduce more case studies in their teaching as to the modules introduce as much much I cothe information and skills§

Innovation & Leadership

Collaborators

Internal Collaborators

Dr Virginie Gautier, CRID Building, UCD, Belfield, Dublin 4

Dr Michael Carr, National Virus Reference Laboratory, UCD, Belfield, Dublin 4.

External Collaborators

Dr Hideki Hasegawa Department of Pathology, National Institute of Infectious Diseases,  Tokyo, Japan with whom I collaborate with on the development of mouse ATL model. The results of some of these studies are included in my publication list.

Professor Kui Li, Dept. of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center
858 Madison Avenue, Memphis, TN 38163, USA. I collaborate with Professor Li concerning cell lines for the propagation of hepatitis C.