Summary
Following graduation with a BSc and PhD in Biochemistry from the University of London, Dr Laki Buluwela went to the MRC Laboratory of Molecular Biology in Cambridge as a Research Fellow and member of staff, working with Professor Terry Rabbitts, FRS and Nobel Laureate Dr Cesar Milstein. In 1993 he joined Professor Charles Coombes in the Department of Oncology at Charing Cross and Westmisnter Medial School, which is now part of Imperial College London. Dr Buluwela has been interested in developing in vitro models for the study of mammary gland morphogenesis and growth, using primary human mammary epithelial cells. As part of this work, he has developed a particular expertise in isolating and purifying both normal and malignant mammary epithelial cells, which have been used in studies of gene expression comparing normal and tumour cell types. His most recent work has centred on developing new techniques for manipulating key genes in cell models and has been carried out in collaboration with Professor Simak Ali and Professor Charles Coombes. This has included the use of viral vectors to over-express genes, such as the oestrogen receptor in primary, normal mammary epithelial cells and the development of a new technology to silence genes, based on chromatin engineering. The later approach is known as "Gene Inactivation by Chromatin Engineering", or "Gene ICE" and has been successfully used to obtain long term gene silencing of oestrogen regulated gene expression in breast cancer cell lines. More recently, this system has been used to identify genes implicated in cell growth in response to estrogen. These genes are potential new targets for breast cancer therapy and include LRH-1, a target being developed in collaboration with medicinal chemistry at Imperial College, South Kensington. Further commercial exploitation of Gene ICE has led to the formation of an Imperial College spin-out company, Gene Expression Technologies, and the formation of a new alliance with Cronos Therapeutics Ltd.
Recent Papers
1. Discovery of a New Class of Liver Receptor Homolog-1 (LRH-1) Antagonists: Virtual Screening, Synthesis and Biological Evaluation.Rey J, Hu H, Kyle F, Lai CF, Buluwela L, Coombes RC, Ortlund EA, Ali S, Snyder JP, Barrett AG. ChemMedChem. 2012 Sep 7. doi: 10.1002/cmdc.201200307. [Epub ahead of print]
Back cover: http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201290058/abstract
2. Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets. Baud MG, Leiser T, Haus P, Samlal S, Wong AC, Wood RJ, Petrucci V, Gunaratnam M, Hughes SM, Buluwela L, Turlais F, Neidle S, Meyer-Almes FJ, White AJ, Fuchter MJ. J Med Chem. 2012 Feb 23;55(4):1731-50. doi: 10.1021/jm2016182. Epub 2012 Feb 9.
3. Ali S, Buluwela L, Coombes RC (2011) Antiestrogens and Their Therapeutic Applications in Breast Cancer and Other Diseases. Annu Rev Med. Jan 27. [Epub ahead of print]. PMID: 21054173
4. Laki Buluwela, Tahereh Kamalati, Andy Photiou, Dean A. Heathcote, Michael D. Jones, and Simak Ali (2010). A Simple Laboratory Practical to Illustrate RNA Mediated Gene Interference Using Drosophila Cell Culture. BAMBED Vol. 38, No. 6, pp. 393–399.
5. Tolhurst RS, Thomas RS, Kyle FJ, Patel H, Periyasamy M, Photiou A, Thiruchelvam PT, Lai CF, Al-Sabbagh M, Fisher RA, Barry S, Crnogorac-Jurcevic T, Martin LA, Dowsett M, Charles Coombes R, Kamalati T, Ali S, Buluwela L (2010) Transient over-expression of estrogen receptor-alpha in breast cancer cells promotes cell survival and estrogen-independent growth. Breast Cancer Res Treat. Aug 22. [Epub ahead of print] PMID: 20730598
6. Thiruchelvam PT, Lai CF, Hua H, Thomas RS, Hurtado A, Hudson W, Bayly AR, Kyle FJ, Periyasamy M, Photiou A, Spivey AC, Ortlund EA, Whitby RJ, Carroll JS, Coombes RC, Buluwela L, Ali S (2010) The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells. Breast Cancer Res Treat. Jul 6. [Epub ahead of print] PMID: 20607599
7. Ngan S, Stronach EA, Photiou A, Waxman J, Ali S, Buluwela L (2009) Microarray coupled to quantitative RT-PCR analysis of androgen-regulated genes in human LNCaP prostate cancer cells. Oncogene. 2009 May 14;28(19):2051-63.
8. Nagy B, Fedonidis C, Photiou A, Wahba J, Paule CC, Ma D, Buluwela L, Nagy I (2009) Capsaicin-sensitive primary sensory neurons in the mouse express N-Acyl phosphatidylethanolamine phospholipase D. Neuroscience. Jun 30;161(2):572-7.
Internal College Contribution
- Faculty of Medicine Lead for Doctoral Degrees http://www2.imperial.ac.uk/blog/fom/2011/12/22/new-fom-lead-for-doctoral-degrees-dr-laki-buluwela/
- MRC DTA Program Director- Imperial College http://www1.imperial.ac.uk/medicine/teaching/studentships/
- MBBS –PhD Program Director http://www3.imperial.ac.uk/ugprospectus/facultiesanddepartments/medicine/mbbsphdmedicine
Member of:
- Postgraduate Research Quality Committee
- Postgraduate Clinical Academic Training Committee
- FoM Postgraduate Committee
- FoM Strategic Education Committee Meeting
- Graduate School Management & Strategy Committee
- HEI working group for Crick PhD program
- GTA Working Party
- China Scholarship selection panel
- GS Special cases panel
- MRC Centenary award selection panel
- Research Integrity Training - Working Party
External Visibility
- External examiner for MRes in Biomedical Science – St Georges’ Medical School, University of London
- Editor Kinome http://versita.com/kinome/
- Regular peer reviewing for journals including Oncogene, JME, Human Molecular Genetics, Endocrinology, PLOS1, Human Mutation
- Keynote speaker – PhD Experience Conference 2012- University of Hull
- Member of the Biochemical Society
Current Teaching - Summary;
Undergraduate;
- MBBS - Year 1 Lecturer and examiner
- MBBS- Year 2 Lecturer, module organiser (Cancer-13 lectures) and examiner
- MBBS- Year 1 and 2 Molecules, Cells and Disease Course Committee
- BSc Biomed Sci- Lecturer
- BSc in Surgery- Cancer module – Lecturer
- BSc in Reproductive Medicine- Cancer module – Lecturer and examiner
Postgraduate -MSc;
- MSc in Molecular Medicine (Imperial College London) Tutor, lecturer, examiner, project supervisor and course organiser
- MSc in Human Genetics- Lecturer, and examiner
- MRes in Biomedical Research – Examiner and project supervisor
- MRes in Cancer Biology- Lecturer
Postgraduate -PhD;
- Supervisor of 6 students
Graduate School:
- PhD thesis writing and workshop (three times per year)
Lee Kong Chian School of Medicine:
- On-line teaching resources – organisation of content and delivery
Publications
Journals
De Marchi T, Lai C-F, Simmons GM, et al., 2024, Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling., Sci Rep, Vol:14
Harrod A, Lai C, Goldsbrough I, et al., 2022, Genome engineering for estrogen receptor mutations reveals differential responses to anti-estrogens and new prognostic gene signatures for breast cancer, Oncogene, Vol:41, ISSN:0950-9232, Pages:4905-4915
Li Z, McGinn O, Wu Y, et al., 2022, ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation, Nature Communications, Vol:13, ISSN:2041-1723, Pages:1-18
Conference
Jurgaityte K, Sava G, Lai CF, et al., 2023, Defining modulators of response to samuraciclib, a CDK7 inhibitor for breast cancer, 114th Annual Meeting of the American Association for Cancer Research (AACR), AMER ASSOC CANCER RESEARCH, ISSN:0008-5472
Patents
HART STEPHEN (GB), ALI SIMAK (GB), PUFONG BORIS T (GB), et al., 2023, Control of gene expression using a complex of an oligonucleotide and a regulatory peptide, US2005136040