Dr Ursula M D'Souza BSc (Hon) PhD
Lecturer in Molecular Genetics
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|tel||020 7848 0741|
Institute of Psychiatry
MRC, SGDP Centre
|departments||Social, Genetic and Developmental Psychiatry (IRG)|
Social, Genetic and Developmental Psychiatry Centre (MRC)
Molecular Genetic Studies
Ursula D’Souza is a lecturer in molecular genetics at the SGDP Centre at the Institute of Psychiatry with experience in molecular biology particularly in the fields of transcriptional regulation and gene expression. Her research focuses on understanding function of genetic variation associated with neuropsychiatric disorders and determining molecular mechanisms in response to pharmacological drug treatment. She has investigated the molecular and cellular effects of genetic variation in regulatory regions of the dopaminergic system and of the serotonergic system associated with ADHD and affective disorders, respectively, using in vitro cell cultures and human brain post-mortem tissue ex vivo (funded by an MRC component grant). Her current research uses cell culture systems to determine the molecular effects of treatment with antidepressant drugs (in vitro component of a large multicentre pharmacogenomic study (GENDEP), funded by the European Union FP6) and mood stabilisers (utilising specific lymphoblastoidal cell lines from clinically depressed subjects collected in the Depression Case Control (DeCC) study). These will aid in identifying drug targets in affective disorders and determine the allele-specific effects of drug treatment on gene expression.
Previously, she received an MRC travelling fellowship in 1998 and an NIH award as a visiting fellow in molecular biology (1999-2000) to work in the Genetic Pharmacology Unit, Experimental Therapeutics Branch at NINDS, NIH in Bethesda, USA. The research focused on the characterisation of the 5’flanking region of the D3 dopamine receptor gene, regulation of dopamine receptors by estrogen and corticosterone and in situ hybridisation expression studies of a novel dopaminergic transcription factor.
In 1995 she moved to the Psychological Medicine department at the University of Wales College of Medicine in Cardiff, where her postdoctorate research in molecular genetics of schizophrenia focused mainly on the regulation of dopamine and serotonin gene expression following antipsychotic treatment.
In 1990, she obtained a bachelor’s honours degree in biochemistry at the University of Kent at Centerbury, England and included an industrial training year in the drug metabolism division at Pfizer, Sandwich, Kent. At Canterbury she continued her postgraduate studies in molecular pharmacology and brain biochemistry where she was awarded her PhD.
Supervision of MSc and PhD projects
Co-scientific director and course leader of the Molecular Genetics part and Microarray/Gene Expression course (2003-2007 and Methods and Applications of Molecular Biomarker Research at the SGDP Centre Summer School (2009). This included teaching of practicals and presentation of lectures on gene expression in neuropsychiatry and the study of promoters.
Annual teaching on the MSc in Research Methods in Psychiatry, Study Units on Brain-Behaviour Interface at IOP 2004-2010. Lecture: Fishing for results: what do proteomics and genomics mean?
|Lecturer||Psychiatric Research » Masters (MSc)|
D’Souza, U.M. & Craig, I.W. (2010). Genetic organization of the serotonergic system. In Handbook of the Behavioural Neurobiology of Serotonin edited by Christian P. Muller and Barry Jacobs published by Elsevier.
D’Souza, U.M. (2010). Gene and promoter structures of the dopamine receptors. In The Dopamine Receptors: Second Edition edited by Kim Neve published by The Humana Press Inc.
Sugden K., Tichopad A., Khan, N, Craig, I.W. and D’Souza U.M. (2009) Genes within the serotonergic system are differentially expressed in human brain. BMC Neuroscience 10:50 doi:10.1186/1471-2202-10-50
Sugden K., Pariante C.M., McGuffin P., and Aitchison K.J., D’Souza U.M. (2008) Housekeeping gene expression is affected by antidepressant treatment in a mouse fibroblast cell line. Journal of Psychopharmacology. Dec 12 [Epub ahead of print].
D’Souza U.M. & Craig I.W. (2008)Functional genetic polymorphisms in serotonin and dopamine gene systems and their significance in behavioural disorders. Progress in Brain Research 172:73-98
Brookes K.J., Neale B.N., Sugden K., Khan N., Asherson P., D’Souza U.M. (2007). Relationship between VNTR polymorphisms of the human dopamine transporter gene and expression in post-mortem midbrain tissue. American J Medical Genetics Part B. Neuropsychiatric genetics 144:1070-1078.
D’Souza U.M. & Craig I.W. (2006). Functional polymorphisms in dopamine and serotonin pathway genes. Human Mutation 27:1-13.
Mill J., Asherson P.J., Craig I.W., D’Souza U.M. (2005). Transient Expression Analysis of Allelic Variants of a VNTR in the Dopamine Transporter Gene (DAT1). BMC Genetics, 6:3
D’Souza U.M., Russ C, Tahir E, Mill J, McGuffin P, Asherson P.J & Craig, I.W. (2004). Functional effects of a tandem duplication polymorphism in the 5’flanking region of the DRD4 gene. Biological Psychiatry 56:691-697.
Parsons M.J, D’Souza U.M., Arranz M-J, Kerwin R.W. & Makoff A.J. (2004). The –1438A/G polymorphism in the 5-hyroxytryptamine type 2A receptor gene affects promoter activity. Biological Psychiatry 56: 406-410.
Fernandes C, Paya-Cano JL, Sluyter F, D’Souza U, Plomin R, Schalkwyk LC. (2004). Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour. Eur J Neurosci. 19: 2576-2582.
Smits, B.M., D’Souza, U.M., Berezikov E, Cuppen E & Sluyter F. (2004). Identifying polymorphisms in the Rattus norvegicus D dopamine receptor gene and regulatory region. Genes Brain Behav. 3:138-48.
D’Souza, U. Book review of The Female Brain ed Cynthia L. Darlington, London, Taylor & Francis, 2002. In Book and Media Reviews, Complied by David Ball in Addiction Biology 9: 87-89 (2004).
D’Souza, U.M., Kel, A. & Sluyter, F. (2003). From transcriptional regulation to aggressive behavior. Behavior Genetics 33: 549-562.
Mill, J., Asherson, P., Browes, C., D’Souza, U. & Craig, I. (2002). Expression of the dopamine transporter gene is regulated by the 3’UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR. American Journal of Medical Genetics 114: 975-979.
D’Souza, U.M., Lammers, C-H., Hwang, C.K., Yajima, S. & Mouradian, M.M. (2002). Developmental expression of the zinc finger transcription factor DRRF (dopamine receptor regulating factor). Mechanisms of Development 110: 197-201.
D’Souza, U. Book review of The Human Brain: essentials of behavioural neuroscience ed J.Beatty, London, Sage Publications Ltd, 2001. In Book and Media Reviews, Compiled by David Ball in Addiction Biology 6: 387-391 (2001).
D’Souza, U.M., Wang, W., Gao, D-Q., Kanda, S., Lee, G., Junn, E., Hwang, C.K., Jose, P.A. & Mouradian, M.M. (2001). Characterization of the 5’flanking region of the rat D3 dopamine receptor gene. Journal of Neurochemistry 76: 1736-1744.
Hwang, C.K., D’Souza, U.M., Eisch, A.J., Yajima, S., Lammers, C-H., Yang, Y., Lee, S-H., Kim, Y-M., Nestler, E.J. & Mouradian, M.M. (2001). Dopamine receptor regulating factor, DRRF: A zinc finger transcription factor. PNAS 98: 7558-7563.
Yang, Y., Hwang, C.K., D’Souza, U.M., Lee, S-H., Junn, E. & Mouradian, M.M. (2000). Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription. Journal of Biological Chemistry 275: 20734-20741.
Lammers, C-H., D’Souza, U. M, Qin, Z-H., Lee, S-H., Yajima, S & Mouradian, M.M (1999) Regulation of striatal dopamine receptors by corticosterone. An in vivo and in vitro study. Mol. Brain Res. 69: 281-285.
Lammers, C-H., D’Souza, U., Qin, Z-H., Lee, S-H., Yajima, S. & Mouradian, M.M (1999) Regulation of striatal dopamine receptors by estrogen. Synapse 34:222-227.
Spurlock, G., Heils, A., Holmans, P., Williams J., D’Souza, U.M., Cardno, A., Murphy, K.C., Jones, L., Buckland, P.R., McGuffin, P., Lesch, K.P. & Owen, M.J. (1998) A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter. Molecular Psychiatry 3(1): 42-49.
Buckland, P.R., D’Souza, U.M., Maher, N.A. & McGuffin, P. (1997) The effects of antipsychotic drugs on the levels of serotonin 5HT2A and 5HT2C receptors. Molecular Brain Research 48: 45-52.
D’Souza, U.M., McGuffin, P. & Buckland, P.R. (1997) Antipsychotic up-regulation of dopamine D1, D2 and D3 dopamine receptor mRNA. Neuropharmacology 36: 1689-1696.
D’Souza, U.M. & Strange, P.G. (1995) The pH dependence of ligand binding to D2 dopamine receptors. Biochemistry 34: 13635-13641.
Vile, J.M., D’Souza, U.M. & Strange, P.G. (1995) [3H]Nemonapride and [3H]spiperone label equivalent numbers of D2 and D3 dopamine receptors in a range of tissues and under different conditions. Journal of Neurochemistry 64: 940-943.
D’Souza U.M, Strange PG. (1992) Structural analysis of the D2 dopamine receptor. Biochem Soc Trans 20:146S
last updated: Tuesday, March 09, 2010