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Dr Shanie Budhram-Mahadeo
Telephone:020 3108 2160
Address:413 MMBU, Rayne Building,
5 University Street ,
Appointments:Lecturer, ICH - Medical Molecular Biology Unit, Dept of Genes, Dev & Disease
Transcriptional regulation of gene expression:
Regulation of gene expression by transcription factors (TFs) is pivotal for determining cell fate during development and normal homeostasis, and de-regulation of gene transcription contribute to many diseases. The homeodomain TFs, POU4F1/Brn-3a (Brn-3a) and related POU4F2/Brn-3b, (Brn-3b), are distinct but related regulators that share high homology in the DNA binding POU domain but differ considerably in other regions. As such, Brn-3a and Brn-3b bind to similar DNA sequences in the promoters of target genes but can give rise to diverse effects on gene expression/cell fate.
However, the effects of these transcription factors are highly dependent on the tissue of expression and growth conditions as well as co-expression with other regulators such as p53. For example, Brn-3a enhances neuronal differentiation by activating synaptic protein SNAP25, neurofilament (NFH); a-internexin etc. and survival by increasing anti-apoptotic Bcl-2 or BclXL whilst repressing p53 mediated pro-apoptotic target genes (Bax and Noxa). In contrast, Brn-3b drives proliferation by activating cell cycle proteins, cyclin D1 and CDK4 but if co-expressed with p53, brn-3b cooperates with p53 to enhance Bax expression and hence apoptosis.
These findings have demonstrated how co-expression of different TFs can influence cell fate. Furthermore the cooperation between Brn-3b and p53 to promote apoptosis may support a novel paradigm for understanding how cells respond to conflicting signals arising from co-expression of Brn-3b which normally stimulates cell proliferation, and p53, which drives cell cycle arrest. Given their complex effects on cell fate, it is necessary to analyse the effects of Brn-3a and Brn-3b in cell/tissue specific context and determine how co-expression with other cellular factors can affect gene expression and cell fate.
Although Brn-3a and Brn-3b have been studied extensively in neuronal cells and retinal ganglion cells, respectively, these TF are expressed in other tissues/system such as the heart and are deregulated in diseases such as cancers. Our primary research in MMBU has focused on studying how transcriptional regulators such as Brn-3a and Brn-3b act in different tissues under normal conditions and identify changes that may contribute to diseases.
- Control of cell fate by regulating gene expression
- Dynamic Loading of Metal-Ceramic Composites
Displaying 50 most recent publications. For the full list please visit UCL Discovery
- Mehta G,Sharma V,Habtesion A,Balasubramaniyan V,Davies NA,Jalan R,Budhram-Mahadeo V,Mookerjee RP (2012) GENE TRANSFER OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE-1 REDUCES PORTAL PRESSURE IN A RODENT MODEL OF CIRRHOSIS GUT, 61, A123 - A123. 10.1136/gutjnl-2012-302514b.123.
- Mehta G,Shah N,Sharma V,Habtesion A,Davies N,Jalan R,Budhram-Mahadeo VS,Mookerjee R (2012) Hepatic Dimethylarginine Dimethylaminohydrolase-1 (DDAH-1) is Decreased in Acute-on-Chronic Liver Failure due to Post-Transcriptional Regulation by an Altered MicroRNA Profile HEPATOLOGY, 56, 739A - 740A.
- Fujita R,Ounzain S,Wang AC,Heads RJ,Budhram-Mahadeo VS (2011) Hsp-27 induction requires POU4F2/Brn-3b TF in doxorubicin-treated breast cancer cells, whereas phosphorylation alters its cellular localisation following drug treatment. Cell Stress Chaperones, 16(4), 427 - 439. 10.1007/s12192-011-0256-8.
- Ounzain S,Bowen S,Patel C,Fujita R,Heads RJ,Budhram-Mahadeo VS (2011) Proliferation-associated POU4F2/Brn-3b transcription factor expression is regulated by oestrogen through ERα and growth factors via MAPK pathway. Breast Cancer Res, 13(1), R5. 10.1186/bcr2809.
- Berwick DC,Diss JK,Budhram-Mahadeo VS,Latchman DS (2010) A simple technique for the prediction of interacting proteins reveals a direct Brn-3a-androgen receptor interaction. J Biol Chem, 285(20), 15286 - 15295. 10.1074/jbc.M109.071456.
- Budhram-Mahadeo V (2008) TRANSCRIPTIONAL REGULATOR, BRN-3B/POU4F2 AND ITS TARGET GENES IN CONTROLLING GROWTH AND BEHAVIOUR OF BREAST CANCER CELLS ANTICANCER RES, 28(5C), 3224 - 3224.
- Hudson CD,Sayan AE,Melino G,Knight RA,Latchman DS,Budhram-Mahadeo V (2008) Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription Cell Death and Differentiation, 15(8), 1266 - 1278.
- Budhram-Mahadeo VS,Irshad S,Bowen S,Lee SA,Samady L,Tonini GP,Latchman DS (2008) Proliferation-associated Brn-3b transcription factor can activate cyclin D1 expression in neuroblastoma and breast cancer cells Oncogene, 27, 145 - 154.
- Farooqui-Kabir SR,Diss JKJ,Henderson D,Marber MS,Latchman DS,Budhram-Mahadeo V,Heads RJ (2008) Cardiac expression of Brn-3a and Brn-3b POU transcription factors and regulation of Hsp27 gene expression Cell Stress and Chaperones, 13(3), 297 - 312.
- Chantelle Hudson GM,A Emre Sayan DSLAB-M,V (2006) Brn-3a Transcription Factor binds p73 to regulate survival and cell cycle arrest in neuronal cells Molecular and Cellular Biology.
- Budhram-Mahadeo V (2006) Targeting Brn-3b in breast cancer therapy" Invited review to Expert Opinion on Therapeutic Targets Expert Opinion on Therapeutic Targets, 10(1), 15 - 25.
- Budhram-Mahadeo VS,Latchman DS (2006) Targeting Brn-3b in breast cancer therapy Expert Opinion on Therapeutic Targets, 10(1), 15 - 25.
- Ndisang D,Faulkes DJ,Gascoyne D,Lee SA,Ripley BJ,Sindos M,Singer A,Budhram-Mahadeo V,Cason J,Latchman DS (2006) Differential regulation of different human papilloma virus variants by the POU family transcription factor Brn-3a Oncogene, 25(1), 51 - 60.
- Budhram-Mahadeo VS,Bowen S,Lee S,Perez-Sanchez C,Ensor E,Morris P,Latchman D (2006) Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of cell cycle arrest by co-operating in transactivation of bax expression Nucleic Acids Research, 34(22), 6640 - 6652.
- Diss JKJ,Faulkes DJ,Walker MM,Patel A,Foster CS,Budhram-Mahadeo V,Djamgoz MBA,Latchman DS (2006) Brn-3a neuronal transcription factor functional expression in human prostate cancer Prostate Cancer and Prostatic Diseases, 9, 83 - 91.
- Samady L,Faulkes DJ,Budhram-Mahadeo V,Ndisang D,Potter E,Brabant G,Latchman DS (2006) The Brn-3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells International Journal of Cancer, 118(4), 869 - 878.
- Diss JK,Faulkes DJ,Walker MM,Patel A,Foster CS,Budhram-Mahadeo V,Djamgoz MB,Latchman DS (2006) Brn-3a neuronal transcription factor functional expression in human prostate cancer. Prostate Cancer Prostatic Dis, 9(1), 83 - 91. 10.1038/sj.pcan.4500837.
- Lee SA,Budhram-Mahadeo VS (2005) Brn-3b transcription factor in breast tumourigenesis: regulation of genes associated with growth and migration of cancer cells Breast Cancer Research, 7, S58 - S59.
- Samady LF,D J Budhram-Mahadeo VN,D Potter EB,G Latchman DS (2005) The Brn-3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells International Journal of Cancer.
- Diss JK,Faulkes DJ,Walker MM,Patel A,Foster CS,Budhram-Mahadeo V,Djamgoz MB,Latchman DS (2005) Brn-3a neuronal transcription factor functional expression in human prostate cancer PROSTATE CANCER PROSTATIC DIS.
- Lee SA,Ndisang D,Patel C,Dennis JH,Faulkes DJ,D'Arrigo C,Samady L,Farooqui-Kabir S,Heads RJ,Latchman DS,Budhram-Mahadeo VS (2005) Expression of the Brn-3b Transcription Factor Correlates with Expression of HSP-27 in Breast Cancer Biopsies and Is Required for Maximal Activation of the HSP-27 Promoter Cancer Research, 65(8), 3072 - 3080.
- Irshad S,Pedley RB,Anderson J,Latchman DS,Budhram-Mahadeo V (2004) The Brn-3b transcription factor regulates the growth, behavior, and invasiveness of human neuroblastoma cells in vitro and in vivo Journal of Biological Chemistry, 279(20), 21617 - 21627. 10.1074/jbc.M312506200.
- Samady L,Dennis J,Budhram-Mahadeo V,Latchman DS (2004) Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU family transcription factor Cancer biology and therapy, 3, 317 - 323.
- Hudson CD,Podesta J,Henderson D,Latchman DS,Budhram-Mahadeo V (2004) Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis Journal of Neuroscience Research, 78(6), 803 - 814.
- Farooqui-Kabir SR,Budhram-Mahadeo V,Lewis H,Latchman DS,Marber MS,Heads RJ (2004) Regulation of Hsp27 expression and cell survival by the POU transcription factor Brn3a CELL DEATH DIFFER, 11(11), 1242 - 1244.
- Hudson CD,Morris PJ,Latchman DS,Budhram-Mahadeo VS (2004) Brn-3a transcription factor blocks p53 mediated expression of pro-apoptotic target genes, Noxa and Bax, in-vitro and in-vivo to determine cell fate Journal of Biological Chemistry.
- (2002) Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter Nucleic Acids Research, 30(22), 4872 - 4880.
- (2002) Functional interaction between Brn-3a and SRC-1 co-activates Brn-3a-mediated transactivation Biochemical and Biophysical Research Communications, 294(2), 487 - 495.
- Budhram-Mahadeo V,Morris P,Ndisang D,Irshad S,Lozano G,Pedley B,Latchman DS (2002) The Brn-3a POU family transcription factor stimulates p53 gene expression in human and mouse tumour cells. Neuroscience Letters, 334(1), 1 - 4.
- Budhram-Mahadeo V,Morris PJ,Latchman DS (2002) The Brn-3a transcription factor inhibits the pro-apoptotic effect of p53 and enhances cell cycle arrest by differentially regulating the activity of the p53 target genes encoding Bax and p21(CIP1/Waf1) Oncogene, 21(39), 6123 - 6131. 10.1038/sj.onc.1205842.
- (2001) The closely related POU family transcription factors Brn-3a and Brn-3b are expressed in distinct cell types in the testis The International Journal of Biochemistry and Cell Biology, 33(10), 1027 - 1039.
- Ndisang D,Budhram-Mahadeo V,Pedley RBAL,D S (2001) The Brn-3a transcription factor plays a key role in regulating the growth of cervical cells in vivo. Oncogene, 20, 4899 - 4903.
- Dennis JH,Budhram-Mahadeo V,Latchman DS (2001) The Brn-3b POU family transcription factor regulates the cellular growth, proliferation, and anchorage dependence of MCF7 human breast cancer cells ONCOGENE, 20(36), 4961 - 4971.
- (2001) A minimal Bcl-x promoter is activated by Brn-3a and repressed by p53 Nucleic Acids Research, 29(22), 4530 - 4540.
- Ndisang D,Budhram-Mahadeo V,Pedley B,Latchman DS (2001) The Brn-3a transcription factor plays a key role in regulating the growth of cervical cancer cells in vivo ONCOGENE, 20(35), 4899 - 4903.
- Ndisang D,Budhram-Mahadeo V,Singer A,Latchman DS (2000) Widespread elevated expression of the human papillomavirus (HPV)-activating cellular transcription factor Brn-3a in the cervix of women with CIN3 (cervical intraepithelial neoplasia stage 3) Clinical Science, 98, 601 - 602.
- Ndisang D,Budhram-Mahadeo V,Latchman DS (1999) The Brn-3a transcription factor plays a critical role in regulating human papilloma virus gene expression and determining the growth characteristics of cervical cancer cells. J Biol Chem, 274(40), 28521 - 28527.
- Budhram-Mahadeo VS,Ndisang D,Ward T,Weber BL,Latchman DS (1999) The Brn-3b POU family transcription factor represses expression of the BRCA-1 anti-oncogene in breast cancer cells Oncogene, 18, 6684 - 6691.
- Budhram-Mahadeo VS,Morris PJ,Smith MD,Midgeley CA,Boxer LM,Latchman DS (1999) p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor Journal of Biological Chemistry, 274, 15237 - 15244.
- Budhram-Mahadeo V,Parker M,Latchman DS (1998) POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element. Mol Cell Biol, 18(2), 1029 - 1041.
- Latchman DS,Budhram-Mahadeo V,Parker M (1998) The POU domain factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an ERE Molecular and Cellular Biology, 18, 1029 - 1041.
- Budhram-Mahadeo V,Parker M,Latchman DS (1997) The POU domain factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an ERE Molecular And Cellular Biology, 18, 1029 - 1041.
- Budhram-Mahadeo V,Morris PJ,Lakin ND,Dawson SJ,Latchman DS (1996) The different activities of the two activation domains of the Brn-3a transcription factor are dependent on the context of the binding site. J Biol Chem, 271(15), 9108 - 9113.
- Budhram-Mahadeo V,Lillycrop KA,Latchman DS (1995) The levels of the antagonistic POU family transcription factors Brn-3a and Brn-3b in neuronal cells are regulated in opposite directions by serum growth factors. Neurosci Lett, 185(1), 48 - 51.
- Budhram-Mahadeo V,Morris PJ,Lakin ND,Theil T,Ching GY,Lillycrop KA,Möröy T,Liem RK,Latchman DS (1995) Activation of the alpha-internexin promoter by the Brn-3a transcription factor is dependent on the N-terminal region of the protein. J Biol Chem, 270(6), 2853 - 2858.
- Budhram-Mahadeo V,Theil T,Morris PJ,Lillycrop KA,Moroy T,Latchman DS (1994) The DNA target site for the Brn-3 POU family transcription factors can confer responsiveness to cyclic AMP and removal of serum in neuronal cells. Nucleic Acids Res, 22(15), 3092 - 3098.
- Budhram-Mahadeo V,Lillycrop KA,Latchman DS (1994) Cell cycle arrest and morphological differentiation can occur in the absence of apoptosis in a neuronal cell line. Neurosci Lett, 165(1-2), 18 - 22.
- Lillycrop KA,Budrahan VS,Lakin ND,Terrenghi G,Wood JN,Polak JM,Latchman DS (1992) A novel POU family transcription factor is closely related to Brn-3 but has a distinct expression pattern in neuronal cells. Nucleic Acids Res, 20(19), 5093 - 5096.
- Budhram-Mahadeo V,Ounzain S,Fujita R,Heads RJ POU4F2/Brn-3b transcription factor in cardiac hypertrophy.
- Budhram-Mahadeo V Do Brn’s rule the heart? Brn-3 TFs in cardiac development, defects/disease.
- 1995: Doctor of Philosophy, University of London
- 1990: Bachelor of Science (Honours), University of East London
- 1986: Registered General Nurse, Ealing General Hospital
- Axon degeneration
- Axon regeneration
- Breast cancer
- Cancer cell cycle
- Cancer protein-protein interaction
- Cell culture
- Gene expression profiling - tissue level
- Gene regulation
- Genetic manipulation (including knockout/knockin)
- Neurodegenerative diseases
- Recombinant protein expression
- Spinal cord injury
- Transcription factor
- Transcription factors in development and diseases
- Transgenic mice
- cardiac development
- cardiac hypertrophy
- neuronal development and differentiation