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Dr Sandra Healy

PhD

 
researcher
 

Biography

My research interests over the past 15 years have been primarily in the field of cancer research. After completing my PhD I moved to the UK where I studied the mechanisms regulating cell division and the response to DNA damage in research institutes (Cancer research UK, Clare Hall laboratories) and universities (Cambridge University) and then continued this work at the University of Milan, Italy.  Following my postdoctoral studies I worked as a research scientist in industry where I contributed to the development of novel cancer chemotherapeutic agents (Pharmacia/ Pfizer/ Nerviano Medical Sciences). In Industry I set up and ran a Microarray laboratory where we studied late stage compounds that the company had approved for phase 1 clinical studies. I analysed the effects of these compounds on the gene expression profile of cells to further characterise their mechanism of action and to develop biomarkers that would allow us to follow the activity of these compounds in clinical studies.

On returning to Ireland in 2007 I worked for two years as a research manager/scientific reviewer in Prof. Afshin Samali’s group at NUIG and contributed significantly to writing research and review articles, grant proposals and reports. More recently I am working as University Teacher which involves teaching Biochemistry to Medical students and Nursing students. I plan and coordinate the delivery of courses which involves lecturing, running practical laboratories and tutorials and coordinating staff, timetables, exams etc. At the same time I am integrated into research activities of the laboratories of both Prof. Afshin Samali and Prof. Corrado Santocanale (working on apoptosis and DNA replication) where I contribute to writing papers and reviews, participate in lab meetings and student supervision and contribute to writing grant applications.

Research Interests

My research activities are primarily in the field of cancer research. I am interested in understanding basic biological mechanisms related to cellular stress responses and how we can target these mechanisms to selectively kill cancer cells.

Cells are continually exposed to stress – this stress can originate from inside the cell (e.g. errors made in protein folding or errors made in replicating DNA) or it may originate from the external environment (e.g. UV irradiation, drugs or a lack of oxygen). Stressed cells initially attempt to overcome the stress and promote survival by selectively producing or activating proteins to repair the damage. However if the stress is overwhelming and cannot be repaired cells initiate the apoptotic cell death pathway. Cancer cells proliferate rapidly and hence they have a huge demand on DNA replication and protein and lipid production as well as being frequently exposed to hypoxia and nutrient starvation. To cope with these stresses cancer cells frequently activate the survival arm of the stress response while inactivating the apoptosis induction arm of the stress response by mutating key death inducing proteins.

My research is focused on understanding these stress responses and identifying proteins in the response pathways that could be targeted to selectively kill cancer cells while leaving normal cells unharmed.

Peer Reviewed Journals

  Year Publication
(2014) 'Stressed to death - mechanisms of ER stress-induced cell death'
Sovolyova, N,Healy, S,Samali, A,Logue, SE (2014) 'Stressed to death - mechanisms of ER stress-induced cell death'. Biological Chemistry, 395 (1):1-13 [DOI] [Details]
(2014) 'A High Through-Put Screen for Small Molecules Modulating MCM2 Phosphorylation Identifies Ryuvidine as an Inducer of the DNA Damage Response'
FitzGerald, J,Murillo, LS,O'Brien, G,O'Connell, E,O'Connor, A,Wu, K,Wang, GN,Rainey, MD,Natoni, A,Healy, S,O'Dwyer, M,Santocanale, C (2014) 'A High Through-Put Screen for Small Molecules Modulating MCM2 Phosphorylation Identifies Ryuvidine as an Inducer of the DNA Damage Response'. Plos One, 9 [DOI] [Details]
(2013) 'Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models'
Natoni A, Coyne MR, Jacobsen A, Rainey MD, O'Brien G, Healy S, Montagnoli A, Moll J, O'Dwyer M, Santocanale C (2013) 'Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models'. Cancers, 5 (3):901-918 [DOI] [Details]
(2013) 'Structural determinants of DISC function: New insights into death receptor-mediated apoptosis signalling'
Sessler T, Healy S, Samali A, Szegezdi E. (2013) 'Structural determinants of DISC function: New insights into death receptor-mediated apoptosis signalling'. Pharmacology & therapeutics, 1 (1):1-1 [DOI] [Details]
(2012) 'Stress management at the ER: regulators of ER stress-induced apoptosis'
Gorman AM, Healy SJ, Jäger R, Samali A (2012) 'Stress management at the ER: regulators of ER stress-induced apoptosis'. Pharmacology & therapeutics, 134 (3):306-316 [DOI] [ARAN Link] [Details]
(2012) 'Transcriptional analysis of the Aurora inhibitor Danusertib leading to biomarker identification in TP53 wild type cells'
Bosotti R, Carpinelli P, Healy S, Locatelli G, Cappella P, Lanfrancone L, Calogero R, Moll J and Isacchi A (2012) 'Transcriptional analysis of the Aurora inhibitor Danusertib leading to biomarker identification in TP53 wild type cells'. Gene, 494 (2):202-208 [Details]
(2012) 'Stress management at the ER: regulators of ER stress-induced apoptosis'
Gorman AM, Healy SJM, Jäger R, Samali A (2012) 'Stress management at the ER: regulators of ER stress-induced apoptosis'. Pharmacology And Therapeutics, [Details]
(2011) 'Summarizing Probe Intensities of Affymetrix GeneChip 3 ' Expression Arrays Taking into Account Day-to-Day Variability'
Magni, P,Simeone, A,Healy, S,Isacchi, A,Bosotti, R (2011) 'Summarizing Probe Intensities of Affymetrix GeneChip 3 ' Expression Arrays Taking into Account Day-to-Day Variability'. Ieee-Acm Transactions On Computational Biology And Bioinformatics, 8 :1425-1430 [DOI] [Details]
(2011) 'Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders'
Doyle KM, Kennedy D, Gorman AM, Gupta S, Healy SJ, Samali A (2011) 'Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders'. Journal Of Cellular And Molecular Medicine, 15 (10):2025-2039 [DOI] [Details]
(2010) 'Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization'
Gupta S, Cuffe L, Szegezdi E, Logue SE, Neary C, Healy S, Samali A (2010) 'Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization'. Journal Of Cell Biology, 2010 [DOI] [Details]
(2010) 'Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization.010; PubMed Central PMCID: PMC2821636'
Gupta S, Cuffe L, Szegezdi E, Logue SE, Neary C, Healy S, Samali A. (2010) 'Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization.010; PubMed Central PMCID: PMC2821636'. Int J Cell Biol, [ARAN Link] [Details]
(2009) 'Targeting the endoplasmic reticulum-stress response as an anticancer strategy'
Healy SJ, Gorman AM, Mousavi-Shafaei P, Gupta S, Samali A. (2009) 'Targeting the endoplasmic reticulum-stress response as an anticancer strategy'. European Journal Of Pharmacology, [Details]
(2008) 'A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity'
Montagnoli, A,Valsasina, B,Croci, V,Menichincheri, M,Rainoldi, S,Marchesi, V,Tibolla, M,Tenca, P,Brotherton, D,Albanese, C,Patton, V,Alzani, R,Ciavolella, A,Sola, F,Molinari, A,Volpi, D,Avanzi, N,Fiorentini, F,Cattoni, M,Healy, S,Ballinari, D,Pesenti, E,Isacchi, A,Moll, J,Bensimon, A,Vanotti, E,Santocanale, C (2008) 'A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity'. Nature Chemical Biology, 4 :357-365 [DOI] [Details]
(2007) 'Cross platform microarray analysis for robust identification of differentially expressed genes'
Bosotti R, Locatelli G, Healy S, Scacheri E, Sartori L, Mercurio C, Calogero R, Isacchi A (2007) 'Cross platform microarray analysis for robust identification of differentially expressed genes'. Bmc Bioinformatics, [DOI] [Details]
(2003) 'Altered cell cycle distribution, hyperplasia, and inhibited differentiation in Arabidopsis caused by the D-type cyclin CYCD3'
Dewitte W, Riou-Khamlichi C, Scofield S, Healy JM, Jacqmard A, Kilby NJ, Murray JA (2003) 'Altered cell cycle distribution, hyperplasia, and inhibited differentiation in Arabidopsis caused by the D-type cyclin CYCD3'. Plant Cell, 15 (1):79-92 [DOI] [Details]
(2001) 'Cell cycle regulation of cyclin-dependent kinases in tobacco cultivar Bright Yellow-2 cells'
Sorrell DA, Menges M, Healy JM, Deveaux Y, Amano C, Su Y, Nakagami H, Shinmyo A, Doonan JH, Sekine M, Murray JA (2001) 'Cell cycle regulation of cyclin-dependent kinases in tobacco cultivar Bright Yellow-2 cells'. Plant Physiol, [DOI] [Details]
(2001) 'The Arabidopsis D-type cyclins CycD2 and CycD3 both interact in vivo with the PSTAIRE cyclin-dependent kinase Cdc2a but are differentially controlled'
Healy JM, Menges M, Doonan JH, Murray JA. (2001) 'The Arabidopsis D-type cyclins CycD2 and CycD3 both interact in vivo with the PSTAIRE cyclin-dependent kinase Cdc2a but are differentially controlled'. J Biol Chem, 276 (10):7041-7047 [DOI] [Details]
(2000) 'Cyclin D control of growth rate in plants'
Cockcroft CE, den Boer BG, Healy JM, Murray JA (2000) 'Cyclin D control of growth rate in plants'. Nature, 405 (6786):575-579 [DOI] [Details]
(2000) 'Sugar control of the plant cell cycle: differential regulation of Arabidopsis D-type cyclin gene expression'
Riou-Khamlichi C, Menges M, Healy JM, Murray JA (2000) 'Sugar control of the plant cell cycle: differential regulation of Arabidopsis D-type cyclin gene expression'. Mol Cell Biol, 20 (13):4513-4521 [DOI] [Details]
(1998) 'The maize retinoblastoma protein homologue ZmRb-1 is regulated during leaf development and displays conserved interactions with G1/S regulators and plant cyclin D (CycD) proteins'
Huntley R, Healy S, Freeman D, Lavender P, de Jager S, Greenwood J, Makker J, Walker E, Jackman M, Xie Q, Bannister AJ, Kouzarides T, Gutiérrez C, Doonan JH, Murray JA (1998) 'The maize retinoblastoma protein homologue ZmRb-1 is regulated during leaf development and displays conserved interactions with G1/S regulators and plant cyclin D (CycD) proteins'. Plant Mol Biol, 37 (1):155-169 [DOI] [Details]
(1996) 'Diagnosis of malignant hyperthermia: A comparison of the in vitro contracture test with the molecular genetic diagnosis in a large pedigree'
Healy, JMS,Quane, KA,Keating, KE,Lehane, M,Heffron, JJA,McCarthy, TV (1996) 'Diagnosis of malignant hyperthermia: A comparison of the in vitro contracture test with the molecular genetic diagnosis in a large pedigree'. Journal Of Medical Genetics, 33 :18-24 [Details]
(1995) 'Haplotype analysis of the BYR1 gene in malignant hyperthermia and central core disease'
Quane KA, Keating KE, Healy JM, Heffron JJ, Lehane M, Krivosic-Horber R, Heytens L, McCarthy TV (1995) 'Haplotype analysis of the BYR1 gene in malignant hyperthermia and central core disease'. Biochemical Society Transactions, 23 (2) [DOI] [Details]
(1994) 'DETECTION OF A NOVEL COMMON MUTATION IN THE RYANODINE RECEPTOR GENE IN MALIGNANT HYPERTHERMIA - IMPLICATIONS FOR DIAGNOSIS AND HETEROGENEITY STUDIES'
QUANE, KA,KEATING, KE,MANNING, BM,HEALY, JMS,MONSIEURS, K,HEFFRON, JJA,LEHANE, M,HEYTENS, L,KRIVOSICHORBER, R,ADNET, P,ELLIS, FR,MONNIER, N,LUNARDI, J,MCCARTHY, TV (1994) 'DETECTION OF A NOVEL COMMON MUTATION IN THE RYANODINE RECEPTOR GENE IN MALIGNANT HYPERTHERMIA - IMPLICATIONS FOR DIAGNOSIS AND HETEROGENEITY STUDIES'. Human Molecular Genetics, 3 :471-476 [Details]
(1994) 'Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores'
Quane KA, Keating KE, Healy JM, Manning BM, Krivosic-Horber R, Krivosic I, Monnier N, Lunardi J, McCarthy TV. (1994) 'Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores'. Genomics, 23 (1):236-239 [DOI] [Details]
(1993) 'MUTATIONS IN THE RYANODINE RECEPTOR GENE IN CENTRAL CORE DISEASE AND MALIGNANT HYPERTHERMIA'
QUANE, KA,HEALY, JMS,KEATING, KE,MANNING, BM,COUCH, FJ,PALMUCCI, LM,DORIGUZZI, C,FAGERLUND, TH,BERG, K,ORDING, H,BENDIXEN, D,MORTIER, W,LINZ, U,MULLER, CR,MCCARTHY, TV (1993) 'MUTATIONS IN THE RYANODINE RECEPTOR GENE IN CENTRAL CORE DISEASE AND MALIGNANT HYPERTHERMIA'. Nature Genetics, 5 :51-55 [Details]
(1990) 'Recent developments in the molecular genetics of malignant hyperthermia: implications for future diagnosis at the DNA level'
McCarthy TV, Healy JM, Lehane M, Heffron JJ. (1990) 'Recent developments in the molecular genetics of malignant hyperthermia: implications for future diagnosis at the DNA level'. Acta Anaesthesiol Belg, 41 (2):107-112 [DOI] [Details]
(1990) 'Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-q13.2'
Healy JM, Lehane M, Heffron JJ, Farrell M, Johnson K, McCarthy TV (1990) 'Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-q13.2'. Biochemical Society Transactions, 18 (2) [DOI] [Details]
(1990) 'Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2'
McCarthy TV, Healy JM, Heffron JJ, Lehane M, Deufel T, Lehmann-Horn F, Farrall M, Johnson K (1990) 'Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2'. Nature, 343 (6258):562-564 [DOI] [Details]

Book Chapters

  Year Publication
(2012) 'Biology of the Endoplasmic Reticulum'
Sandra JM Healy, Tom Verfaillie, Richard Jager, Patrizia Agostinis and Afshin Samali (2012) 'Biology of the Endoplasmic Reticulum' In: ER Stress in Health and Disease. Dordrecht, Netherlands: Springer Science+Business Media. [Details]
(1990) 'Molecular genetics of Malignant Hyperthermia'
McCarthy,T.V., Healy,S.J.M., Lehane, M., Heffron,j.j.a., Deufel, T., Lehmann-Horn,F., Farrell,M and Johnson K (1990) 'Molecular genetics of Malignant Hyperthermia' In: Malignant Hyperthermia, Neuromuscular Diseases and Anaesthesia. Stuggart, New York: Georg Thieme Verlag. [Details]

Conference Publications

  Year Publication
(2014) Irish Association for Cancer Research
Fitzgerald, J; Murillo, L; O’Brien, G; O’Connell, E; O’Connor, A; Wu, K; Wang, GN; Rainey, MD; Natoni, A; Healy, S; O’Dwyer, M; Santocanale, C (2014) A high through put screen identifies Ryuvidine as a modulator of Cdc7 dependent phosphorylation of MCM2 and an inducer of the DNA damage response Irish Association for Cancer Research [Details]

Reviews

  Year Publication
(2011) Unfolded proteins and Endoplasmic Reticulum stress in neurodegenerative disorders.
Doyle KM, Kennedy D, Gorman AM, Gupta S, Healy SJ, Samali A. (2011) Unfolded proteins and Endoplasmic Reticulum stress in neurodegenerative disorders. Reviews [Details]

Professional Associations

  Association Function From / To
European association for Cancer Research member /
Irish Association for Cancer Research member /

Employment

  Employer Position From / To
NUIG University Teacher 15-AUG-08 / 15-MAY-13
University Of Milan, Italy Postdoctoral Fellow 15-JUL-99 / 15-MAY-01
University of Cambridge Postdoctoral Fellow 15-AUG-96 / 15-JUN-99
ICRF (now Cancer research UK) Postdoctoral fellow 15-APR-93 / 12-APR-96
Pharmacia ( then Pfizer and now called Nerviano Medical Sciences), Italy Staff scientist 15-SEP-02 / 15-JUL-07

Education

  Year Institution Qualification Subject
1992 UCC PhD Molecular genetics of Maligant Hyperthermia
1988 UCC BSc Biochemistry

Languages

  Language
Italian

Teaching Interests

I  taught Biochemistry to Medical students and Nursing students at NUIG for three years. I coordinated and taught foundation level Biochemistry courses for both 1st and 2nd year medical students and 1st year nursing students which included module design, delivery, assessment and evaluation as well as  liaising with colleagues in the Schools of Medicine and of Nursing to ensure the smooth running and integration of the courses and participation in regular meetings relating to student performance, assessment, curriculum design and resource needs.


 I lectured, ran practical lab classes, gave tutorials and organised grouped students projects. I am interested in using knowledge from pedagogical research on student learning and curriculum design to improve my teaching practice.  

Modules Taught

  Term/Year Module Title Module Code Subject / Desc
MD138
MD124
NU115
MD121
MD140