Research output per year
Research output per year
Dr
Aston Triangle
B4 7ET Birmingham
United Kingdom
School of Life & Health Sciences, Aston University, Aston Triangle
B4 7ET Birmingham
United Kingdom
Research Overview:
I lead an active DNA repair and genome stability research that focuses on the area of translational approach in novel neuro-regeneration strategies and nanotechnologies for cancer treatment and drug delivery.
Manipulation of DNA damage responses to promote neuroregeneration
The extremely limited regenerative capacity of injured central nervous system axons leads to permanent functional neurological deficits after optic nerve, spinal cord and brain injury. Consequently, enabling axon regeneration after trauma or a disease is a major challenge in neuro-regenerative medicine. Nevertheless, a therapy promoting functional improvements is not available and recently terminated phase I/II clinical trials had not demonstrated any significant improvements. In relation to functionalized NPs project we have discovered that a simple intervention in modulation of DNA damage responses in regenerating neurons resulted in an unprecedented increase in survival, initiation of axonal growth and axon length in experimental ex-vivo models. This is a brand new strategy and we already have an initial in vivo proof that the same principle works in several models of human CNS neurodegenerative conditions, including Alzheimer disease. Optical nerve injury and loss of sight together with neurodegeneration of CNS are all the areas that have significant impact on aging process and as such complement very well the existing and well developed aging-related research themes at Aston University. This area of research has the highest potential for both scientific and commercial impacts and developments as vast numbers of human patients are affected with related conditions and due to the well-known demographic trends these numbers are very likely to be significantly increasing in a near future.
Targeted nanoparticles for experimental cancer therapy
My group have developed several new designs of functionalized gold and platinum nanoparticles (NPs) that combine following properties: (1)Potential for in vivo imaging of targeted tumour cells, (2)Increased target selectivity for cancer cells, (3)Capability to increase the dose efficacy of therapeutic ionizing radiation and ability to inhibit DNA damage responses in targeted cells. Initial results published in Nanomedicine in 2011, followed by a patent in 2013 that had been taken in 2015 into the national phase in Europe, US, China, India and Japan. In the second phase we have focused on the design of nanoparticles with targeting peptides to achieve an autonomous translocation to the cell nucleus in human and mouse model cell lines combined with delivering DNA repair inhibitory factors to sites of DNA damage. This is a technology platform with drug delivery applications reaching beyond cancer therapy field and overlaps very well with research interests with several other groups at Aston University.
We have also developed a method to produce soluble gold-peptides NPs double functionalized with chemotherapeutic drugs, including temozolomide (discovery of which has been historically the major scientific and commercial achievement coming from Aston University) using the same synthetic principles.
This new technology platform has been recently taken for a further commercial development by a specialized preclinical development company with its own venture funding.
The analysis of DSB repair within chromatin:
Nuclear DNA is compacted by association with histone proteins to form chromatin. The compaction of DNA into chromatin affects many, if not all, nuclear processes involving DNA transactions. We try to understand how the complex structural packaging of DNA in chromatin impacts on DSB repair in mammalian cells. We have established a system to investigate the impact of model chromatin substrates on DSB repair that led to the discovery of importance of linker histones for the process (PNAS, 102:1877, 2005). This initial discovery led to the successful project grant funding from BBSRC and the identification of a linker histone variant that is critically required for the outcome of the repair process in human cells (Science, submitted). This novel linker histone function represents an attractive new therapeutic target.
Brief Chronology of Employment:
1994 - 1997 Research Fellow, Imperial Cancer Research Fund, Clare Hall Laboratories
1997 - 2001 Research Fellow, MRC Cell Mutation Unit, University of Sussex
2001 - 2003 Senior Research Fellow, Genome Damage and Stability Centre, University of Sussex
2003 - 2006 Lecturer, the Medical School, University of Birmingham
2006 - 2018 Senior Lecturer in Human Molecular Genetics, College of Medical and Dental Sciences, University of Birmingham
2018 Senior Lecturer in Human Molecular Genetics, Aston Medical School, Aston University
Membership and Participation in Scientific Grant Review Committees:
Member of the Scientific Grant Review Committee for Medicine at European Union Synchrotron Radiation Facility, Grenoble, France.
Member of the Scientific Advisory Review Committee for the Proton Therapy, Ministry of Health, Slovak Republic
MRC Career Development Grant Referee
MRC Research Grants Referee
BBSRC Research Grants Referee
FP-7 Intra-European Fellowship Program Referee
MRC of Singapore Program Grants Referee
INSERM Project Grants Referee
External reviewer:
Journal of Biological Chemistry
Mutation Research
Molecular Biology Reports
International Journal of Radiation Biology
Journal of Theoretical Biology
Nucleic Acid Research
Radiation Research
Journal of Molecular Genetics
Biochimie
Toxicology Letters
Nanomedicine
Oncogene
Successful grants applications:
PhD Studentship Kingdom of Saudi Arabia 2017--2021
PhD Studentship CARA 2016-2020
Dementia Private Fund 2016
MRC Confidence in Concept 2013-214
Russian Federation PhD studentship 2014
Gov of Iraq PhD Studentship 2014
EU ESRF project grant 2012
BWH project grant 2011
EU ESRF project grant 2011
MRC project grant 2009
EU ESRF project grant 2009
BCHRF project grant 2009
Egyptian Department of Health PhD Studentship 2007
MRC/UB PhD Studentship 2006
MRC/EPSRC Discipline Bridging Grants 2006
MRC/EPSRC Discipline Bridging Grant 2005
The BBSRC Project Grant, 2005
The Royal Society Project Grant, 2004
Total funding obtained: £1,272,276
Recent International Conferences (Keynote/invited speaker):
7th International conference on brain and neurological disorders, Amsterdam, Holland April 2018
7th Annual world congress of nanoscience and technology, Fukuoka, Japan 2017
7th European DNA repair workshop, Smolenice 2016
London Chromatin Club conference meeting 2016
3rd International Conference on Nanotechnology in Medicine, Manchester, 2015
International DNA repair meeting, Smolenice, June 2012
International meeting: Nano & Microtechnologies – Medical, Environmental and Electronic Applications, London, October 2010
International conference: “Science with X-ray Nano-beams”, Grenoble, February 2010
Sixth International DNA repair meeting, Smolenice, May 2008
“DNA double-strand break repair in the context of chromatin”, ARR International Meeting, Queens University, Belfast, April 2007
“Proteomics in DNA repair” British Council meeting on Genomics and Proteomics of Cancer, Bratislava March 2007 (Also the main organizer invited by the British Council)
Fourth International DNA repair meeting on DNA damage and repair: mechanisms and biological consequences, May 2004
PhD, Ionizing radiation induced DNA damage and repair in relation to biological function, Brunel University
1 Oct 1991 → 11 Jun 1994
Award Date: 14 Jun 1994
MSc, RNDr. Microbiology, Genetics and Biophysics, Univerzita Karlova
1 Sept 1980 → 11 Jun 1985
Award Date: 11 Jun 1985
Honorary Senior Lecturer in Human Molecular Genetics, University of Birmingham
1 Jul 2018 → …
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Patent