Boris Kysela

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):

7^th International conference on brain and neurological disorders, Amsterdam, Holland April 2018

7^th Annual world congress of nanoscience and technology, Fukuoka, Japan 2017

7^th European DNA repair workshop, Smolenice 2016

London Chromatin Club conference meeting 2016

3^rd 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

• Telephone: 0121 204 3631
• Email: [email protected]
• Room Number: MB314B