Prof. Majlinda Lako
Prof of Stem Cell Science
- Email: majlinda.lako@ncl.ac.uk
- Telephone: 0191 241 8688
- Address: Institute of Human Genetics
International Centre for Life
Central Parkway
Newcastle upon Tyne
NE1 3BZ
Research Interests
Understanding stem cell pluripotency, self-renewal, survival and differentiation, haematopoietic and retinal lineages
Embryonic stem (ES) cells and induced pluripotent stem cells (iPSC) are able to differentiate into several different cell types and as such, they represent an excellent source of cells for continuous cell replacement therapies, drug discovery and basic biology studies. A key to unlocking this potential is the understanding of the critical pathways and factors that are involved in the maintenance of pluripotency and self-renewal as well as differentiation towards specific lineages. While the molecular basis of tissue differentiation in the mouse embryo is well appreciated, the molecular mechanisms of human ES pluripotency are poorly understood. In view of this we have embarked on a major research programme to identify key transcription factors, cell cycle regulators and signalling pathways that are necessary for the maintenance of pluripotency, self-renewal and survival in human ES cells and iPSC. Key to the success of our programme has been the successful establishment of RNAi in human ES cells, stable and efficient genetic manipulation of several transcription factors in several ES cell lines and creation of a large number of ES lines with reporter genes driven from promoters of pluripotent genes or key differentiation factors identified through our large scale transcriptional profiling in human ES cells.
The second research focus in my group has been the derivation of haematopoietic progenitors from human ES cells and iPSC with the aim of generating cells that can be used for curing haematopoietic malignancies as well as understanding the very early haematopoietic development. In the last few years we have devised one of the most efficient protocols for obtaining haematopoietic cells that can engraft successfully in the bone marrow of immunocompromised recipients and contribute to circulation. Currently we are performing large transcriptional functional screens to identify key factors produced by the niche that direct differentiation of human ES cells/iPSC to haematopoietic lineages. In parallel, we are following new pathways of human ES and iPSC differentiation to photoreceptor like cells for treatment of retinal disease.
The third research topic relates to identification of new markers for limbal stem cells, this is a joint project with Dr Sajjad Ahmad & Mr Francisco Figueiredo. To date we have been able to reverse blindness in eight patients with unilateral stem cell deficiency and we are working towards devising new treatment modalities for patients with bilateral disease.
Co-workers
Irina Neganova BSc PhD
Senior Research Associate
Sun Yung BSc MSc
PhD student
Carla Mellough, BSc PhD
Senior Research Associate
Maria Ledran, PhD
Research Associate
Selected Publications
- Zhang X; Neganova I; Przyborski S; Yang CB; Cooke M; Atkinson SP; Anyfantis G; Fenyk S; Keith WN; Hoare SF; Hughes O; Strachan T; Stojkovic M; Hinds PW; Armstrong L; Lako M. A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A. Journal of Cell Biology 2009, 184(1), 67-82.
- Neganova I; Zhang X; Atkinson S; Lako M. Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells. Oncogene 2009, 28(1), 20-30.
- Ledran MH; Krassowska A; Armstrong L; Dimmick I; Renstrom J; Lang R; Yung S; Santibanez-Coref M; Dzierzak E; Stojkovic M; Oostendorp RAJ; Forrester L; Lako M. Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. Cell Stem Cell 2008, 3(1), 85-98.
- Maimets T; Neganova I; Armstrong L; Lako M. Activation of p53 by nutlin leads to rapid differentiation of human embryonic stem cells. Oncogene 2008, 27(40), 5277-5287.
- Armstrong L, Saretzki G, Peters H, Wappler I, Evans J, Hole N, von Zglinicki T and Lako M. “Overexpression of Tert results in enhanced proliferation of murine ES cells, protection from oxidative stress and commitment to haematopoietic lineages”. Stem Cells 23 2005, 23, 516-29.
- Choudhary M; Zhang X; Lako M; Stojkovic M; Murdoch A. "Beauty and Beast'' molecule; HA in early human development. BJOG: An International Journal of Obstetrics and Gynaecology 2009, 116(10), 1408.
