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UCL Institute of Cardiovascular Science

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Molecular biology development and disease

ICS Molecular Biology Development And Disease Group


Lead: Dr Vishwanie (Shanie) Budhram-Mahadeo

Group Members:

Dr Laura Mele (postdoctoral research fellow); Lauren Maskell (PhD student); Vaishaali Yogendran (PhD student); Miroslava Katsur (PhD student); Anupam Mahadeo (visiting student) Clinical Research associate: Gautam Mehta

Location: 3rd floor, UCL Rayne Building

Overview:
Transcriptional regulation of gene expression in health and disease 

Research in the Molecular Biology Development and Disease (MBDD) aims to understand the molecular mechanisms that control cell fate and function under normal conditions but also to identify changes that drive pathological processes associated with diseases. Specifically, this research is focused on analysing the complex and tissue-specific roles for POU4F1/Brn-3a and POU4F2 Brn-3b family of transcription factors, which are known to control diverse cellular events including cell proliferation, apoptosis and differentiation in different cell types. Altered expression of these transcription factors have been implicated in events associated with different human diseases including cancers (tumour growth, drug resistance and metastasis), metabolic dysfunction (type II diabetes/obesity), vascular dysfunction (hypertension) and cardiac response to injury e.g hypertrophy and myocardial infarction (MI). This research utilises a number of model systems e.g. in-vitro cell line or primary cell culture models and in vivo models such as rodents and zebrafish and involve a range of molecular, cellular and imaging techniques.

Current research includes:

1. Using mutant models to identify key regulators of cardiac responses to different stresses e.g. physiological stress (exercise) or pathological stress/injury (coronary artery ligation or volume/pressure overload induced by AngII infusion/aortic banding).

2. Investigating potential compensatory mechanisms that control early heart development using conditional KO mutant and transgenic zebrafish models (generated using CrispR/cas 9 gene editing).

3. Analysing regulators that control glucose intolerance/weight gain and investigating links with Type 2 Diabetes

4. Elucidating the link between metabolic dysfunction and development/progression of vascular defects.

Determining molecular mechanisms driving gene expression changes that prevent calcification and vascular remodelling

5. Investigating crosstalk between immune response and cardio metabolic dysfunction

At present research projects within this group are funded by the BHF and MRC DPT scheme and comprises of one postdoctoral research fellow, three PhD students and clinical research associate/senior lecturer. Many of these studies are carried out in collaboration with other UCL and UK-based researchers as well as international groups. This provides an active research environment for teaching postgraduate students but also for undergraduates to gain insight into research-based projects.

  • Maskell L, Qamar K, Babakr A, Hawkins TA, Heads RJ, and Budhram-Mahadeo V S  2017 Essential but partially redundant roles for POU4F1/Brn-3a and POU4F2/Brn-3b transcription factors in the developing heart Cell Death Dis. 2017 Jun 8;8(6):e2861. doi: 10.1038/cddis.2017.185.
  • Bitsi S, Ali H, Maskell L, Ounzain S, Mohamed-Ali V, Budhram-Mahadeo VS; 2015 Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes.Am J Physiol Endocrinol Metab. 2016 Mar 1;310(5):E303-12. doi: 10.1152/ajpendo.00211.2015. Epub 2015 Dec 15.
  • Budhram-Mahadeo, V., Fujita, R., Bitsi, S., Sicard, P., & Heads, R. (2014). Co-expression of POU4F2/Brn-3b with p53 may be important for controlling expression of pro-apoptotic genes in cardiomyocytes following ischaemic/hypoxic insults.. Cell Death Dis, 5, e1503. doi:10.1038/cddis.2014.452
  • Fujita, R., Ounzain, S., Wang, A. C., Heads, R. J., & Budhram-Mahadeo, V. S. (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. doi:10.1007/s12192-011-0256-8
  • Farooqui-Kabir, S. R., Diss, J. K. J., Henderson, D., Marber, M. S., Latchman, D. S., Budhram-Mahadeo, V., & Heads, R. J. (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.

Highlights: 

Contact details: 

Dr Vishwanie (Shanie) Budhram-Mahadeo
Room 302, 3rd floor UCL Rayne Building 5 University Street London WC1E 6JF v.budhram-mahadeo@ucl.ac.uk
phone: 020 3108 2160