I am a DPhil student in the Wellcome Trust Centre for Human Genetics at University of Oxford under the supervision of Dr. Zoia Larin Monaco since October, 2008. I am currently working on the development of Human Artificial Chromosomes (HACs) in human induced pluripotent stem cells (iPS) and embryonic stem (hES) cells.
Development of artificial chromosomes is considered to be a promising technology with respect to its use in gene based therapeutics. Recent advances in the development of Human Artificial Chromosomes (HACs) as alternative vectors for gene transfer and expression studies in mammalian cells have established their advantages in terms of incorporating large genomic DNA including genes of interest and their regulatory elements, providing independent replication and segregation in the target cells, exhibiting long-term maintenance and overcoming the problems of transgene silencing, cell transformation, toxicity and insertional mutagenesis associated with conventional vectors.
In the recent years it has been shown that induced pluripotent stem cells (iPS), derived by reprogramming of somatic cells, closely resemble ES cells in pluripotency, gene expression and epigenetic states. These cells have great therapeutic potential for regenerative medicine, in vitrodisease modeling and cellular replacement therapies. Developing HACs in iPS cells is of further importance because these cells like ES cells have immense therapeutic significances and patient-specific cells capable of differentiating into any lineage can be created avoiding the ethical hurdles associated with ES cells.
My PhD project is to develop de novo HACs in human iPS and embryonic stem cells, to investigate HAC stability and the expression of target genes. Following are two main aims of my project.
- Evaluate the potential of developing HACs in human iPS and embryonic stem cells and investigating HAC stability, chromosome function and gene expression.
- Investigate the requirements of the Herpes Simplex Virus amplicon (HSV-1) system for HAC delivery into human ES cells and investigate ways to enhance the efficiency of this delivery system using the appropriate modifications.
MANDEGAR, M. A., MORALLI, D., KHOJA, S., COWLEY, S., CHAN, D. Y., YUSUF, M., MUKHERJEE, S., BLUNDELL, M. P., VOLPI, E. V., THRASHER, A. J., JAMES, W. & MONACO, Z. L. (2011) Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells. Hum Mol Genet, 20, 2905-13.
MORALLI, D., YUSUF, M., MANDEGAR, M. A., KHOJA, S., MONACO, Z. L. & VOLPI, E. V. (2011) An improved technique for chromosomal analysis of human ES and iPS cells. Stem Cell Rev, 7, 471-7.
RAI, M. A., NERURKAR, V. R., KHOJA, S., KHAN, S., YANAGIHARA, R., REHMAN, A., KAZMI, S. U. & ALI, S. H. (2010) Evidence for a "Founder Effect" among HIV-infected injection drug users (IDUs) in Pakistan. BMC Infect Dis, 10, 7.
KHOJA, S., OJWANG, P., KHAN, S., OKINDA, N., HARANIA, R. & ALI, S. (2008) Genetic analysis of HIV-1 subtypes in Nairobi, Kenya. PLoS One, 3, e3191.
Clarendon Fund Scholarship
Keble College Sloane Robinson Scholarship
The Wellcome Trust Centre for Human Genetics,
Oxford, OX3 7BN, UK
Email: suhail (at) well.ox.ac.uk
Oxford, OX1 3PG, UK