* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Hasan Y. Alniss
Survey
Document related concepts
History of molecular evolution wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
Community fingerprinting wikipedia , lookup
Gel electrophoresis of nucleic acids wikipedia , lookup
Molecular cloning wikipedia , lookup
Clinical neurochemistry wikipedia , lookup
Ligand binding assay wikipedia , lookup
Molecular evolution wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Deoxyribozyme wikipedia , lookup
Transcript
Hasan Y. Alniss Current address: University of Toronto Leslie Dan Faculty of Pharmacy 144 College Street, room 1170 Toronto, Ontario, M5S 3M2, Canada mobile: 001 6477019817 [email protected] Home Address: An-Najah National University Faculty of Medicine and Health Sciences Department of Pharmacy Nablus, Palestine [email protected] PERSONAL INFORMATION Born: 3 June 1978, Toulkarm, Palestine. Nationality: Palestinian & Jordanian Marital status: Married; Children: Dana, Dema, Yaser & Sama. EDUCATION 11/2007-12/2010 Strathclyde Institute of Pharmacy and Biomedical Sciences Glasgow-UK PhD in Pharmacy and Biomedical Sciences (Medicinal Chemistry) Thesis title: “Biophysical characterization of the processes that drive ligand associations with the minor groove of DNA”. Supervisors: Prof Simon Mackay and Dr Nial Wheate. Project description: The cationic lexitropsins, which bind non-covalently to the minor groove of DNA, have shown therapeutic potential in the treatment of cancer, viral and bacterial diseases. Understanding the factors that drive ligand-DNA associations, particularly the structural features, molecular forces and the energetics that dictate the overall binding process is of fundamental scientific interest as well as a prerequisite for the rational design and development of novel drugs. In this study, a holistic approach was followed to tackle this issue by combining thermodynamic and structural studies to gain insight into the factors that drive lexitropsin-DNA interactions by using different biophysical techniques. In this project, DNA binding agents were synthesized and the complexes they form with DNA were characterized by using different biophysical techniques. Isothermal titration calorimetry (ITC) and circular dichroism (CD) were used to obtain a complete thermodynamic profile for lexitropsin interactions with different ODN sequences and that included the determination of the binding affinity (K), stoichiometry (n), enthalpy (∆H), entropy (∆S) and free energy of binding (∆G). The thermodynamic studies aimed to reveal the molecular forces that drive the binding and to establish a link between the structure and the binding affinity by studying thermodynamic binding characteristics of closely related ligand structures to a specific binding site. NMR spectroscopy and restrained molecular dynamics simulations were used to obtain structural details for lexitropsin-DNA complexes. The NMR NOE derived inter-proton distances were used to generate three dimensional structures for these complexes via the restrained molecular dynamic simulations. The location of the binding site was determined by measuring the changes in chemical shifts of DNA protons upon ligand binding. The work also included synthesis of alkenelinked minor groove binders (MGBs) to investigate the role of the traditional amide links of these MGBs in the binding process. 09/2006-09/2007 Strathclyde Institute of Pharmacy and Biomedical Sciences Glasgow-UK MSc. in Pharmaceutical Analysis with Distinction The courses were taught over two blocks of instructional classes followed by a three month long Page 1 of 7 full-time research project. The course presented the fundamental scientific principles of pharmaceutical analysis and it aimed to provide students with the theoretical and practical knowledge of the chemical, physical and statistical methods required to assess the quality of medicines. Main coursework included separation techniques, chemical analysis, GMPs, GLPs, SOPs, ICH guidelines, validation of analytical methods, structural elucidation of medicines, statistical analysis of data, quality and management, biopharmaceutical analysis, quantitative spectroscopy and drug instability. Research project: “MALDI imaging and analysis of minor groove binders by ESI-MS”. Supervisor: Dr David G. Watson Project description: MALDI imaging is a new technology which can be used for direct analysis of pharmaceuticals and biomolecules in biological tissue sections. This project aimed to use this technique to determine whether or not clozapine can be seen at physiological relevant levels with MALDI-MS imaging in brain tissue sections of rats and to determine the level of detection that can be achieved. The selection of a suitable MALDI matrix plays an important role for a successful analysis. Therefore, one of the aims of this project is to determine the best matrix for this application. The second part of this project was about the analysis of minor groove binders(MGBs) by ESIMS. The use of ESI-MS for the detection and characterisation of non-covalent complexes of biomolecules is an emerging field and there are numerous examples of non-covalent interactions that have been studied in the gas phase such as the interactions between drugs and DNA. In this project, ESI-MS was used to study the non-covalent interactions between MGBs (distamycin analogues) and different ODN duplexes in order to determine affinity, stoichiometry and sequence selectivity of these ligands with different DNA sequences. 09/1996-02/2001 An-Najah National University Nablus-Palestine BSc. in Pharmacy Accumulative Average: 83.5%. Rating: Very good. Main coursework included Clinical pharmacology, pharmacokinetics, industrial pharmacy, pharmaceutical technology, pharmaceutics, organic chemistry, instrumental analysis, phytochemistry, and medicinal chemistry. EMPLOYMENT HISTORY 08/2013-07/2014 Leslie Dan Faculty of Pharmacy-University of Toronto Toronto-Canada Visiting Prfessor Research Project: “Characterization of the factors that stabilize DNA Quadruplexes” with Prof. Rob Macgregor. Teaching: Pharmacy students (student number: 250), Taught topics: Drugs that target nucleic acids, physical incompatibility of drugs & the pharmaceutics injectable formulations. 02/2011– present An-Najah National University-Department of pharmacy Nablus-Palestine. Assistant Professor Taught courses: Medicinal Chemistry (I, II and III), Organic Chemistry (I & II),Organic Chemistry Lab (I) and Quality Control of drugs. (average class size: 50 student) Page 2 of 7 11/2007 – 01/2011 University of Strathclyde Glasgow-UK. Teaching Assistant Whilst undertaking my PhD, I have constantly been involved with the supervision of undergraduates in their practical and theoretical classes. Supervised classes includes : Biopharmacy, Fundamental of Pharmacology and Physiology. 01/2004 -09/2006 Qalqilia Health Department Palestine Pharmaceutical Inspector My work aimed to ensure that pharmacists in private and public sector comply with the laws and regulations of good pharmacy practice. 02/2001 - 12/2003 Qalqilia Health Department Palestine Community Pharmacist Duties: Drug dispensing and patient counseling. RESEARCH EXPERIENCE Technical skills & competences During my postgraduate & postdoctoral studies, I have developed my knowledge of several powerful analytical techniques through the extensive range of equipment available at the university, such as : NMR Spectroscopy (small and macromolecules) and molecular modeling. Isothermal titration calorimetry (ITC). Mass spectrometry (MS). Chromatography instrumentation techniques (GC/MS, LC-ESI/High- resolution MS). Chromatography separation (TLC, HPLC and GC). Capillary electrophoresis, gel electrophoresis & MALDI imaging.. Circular dichroism (CD) & fluorescence spectroscopy. UV-Visible and IR spectroscopy. Research interests Biophysical characterization of ligand-DNA associations by using different analytical techniques (NMR, ITC, CD, ESI-MS & MM). Drug discovery and development Synthesis of DNA binding agents to treat genetic diseases such as cancer. Characterization of the factors that stabilize DNA Quadruplexes Development of non-viral gene delivery vehicles Molecular modeling of ligand-nucleic acids interactions. Pharmaceutical analysis. Supervised M.Sc. projects “Synthesis of amide-linked minor groove binders (MGBs) to target the Androgen Response Element Sequence”. Saber Abu Jabal “Synthesis and biological activity of Distamycin analogues”. Sumood Yassin Important research contributions Two articles that combine simulation and experiment to study the binding thermodynamics of ligand-DNA interactions were published in an international peer-reviewed journal. After one year of work at Prof Mackay’s Lab, I was an author on our invited publication in a special edition of Phys. Chem. Chem. Phys. focussed on nucleic acids (Vol 11 (45)). Authors in this themed edition included the Nobel Laureate for Chemistry, Ahmed Zewail, and our work was selected for the Page 3 of 7 front cover of the journal Phys Chem. Chem. Phys. (2009),11(45), 10529. Since publishing this work, I went on to apply isothermal titration calorimetry, circular dichroism and NMR techniques to compare and rank the affinity of ligands binding to the minor groove of DNA, which is proving to be very useful to the synthetic chemistry team in directing the medicinal chemistry optimization programme. This work was published in the American Chemical Society Journal, Med. Chem. Lett., 2010, 1 (8), 376-380. Another two articles that exploit NMR spectroscopy to solve the 3D solution structure of ligandDNA complexes were published in high impact factor international journals. I established collaboration with Dr. John A. Parkinson from the Department of Pure and Applied ChemistryUniversity of Strathclyde in order to use macromolecular NMR to solve the 3D solution structure of drug-nucleic acid complexes via the restrained molecular dynamic simulations. This work was published in Chemical Science, 2012, 3, 711-722 (impact factor: 8.314) and Biophysical Chemistry. 2013, 179, 1–11. A third paper has been recently submitted to the journal Chemistry: A European Journal, 2014. The outcome of my research is of great importance in terms of both the development of new compounds to target specific genes and to gain more insight into the molecular basis of minor groove recognition by small drug molecules. New compounds with small molecular weight were proposed based on these results to tackle the regulatory region (WGWWCW, W is A or T) for the gene expression of the prostate-specific antigen (PSA) associated with prostate cancer. The ultimate goal of this research is to regulate the expression of defected genes by synthetic DNA binding agents in order to treat genetic diseases such as cancer. The following key words describe my expertise: medicinal chemistry, multi-step synthetic organic chemistry, biophysical Analysis of Ligand-Macromolecules interactions, drug discovery, structure activity relationships, molecular modeling, nucleic acids structure, pharmaceutical analysis & quality control, separation techniques, 2D NMR spectroscopy, isothermal titration calorimetry, circular dichroism. Research Funding History Distinguished Scholar Award 2013/8 - 2014/6 University of Toronto- Canada Funding source: Arab Fund for Economic & Social Development- Fellowships Program Safat 13080 Kuwait, State of Kuwait Total funding: $65000 (United States dollar) Funding competitive?: Yes, this fund is open to all academics working in Arabic Universities University of Strathclyde Research Scholarship 2007/09-2010/09 University of Strathclyde-UK Funding source: University of Strathclyde, SIPBS, 27 Taylor Street, Glasgow G4 0NR, UK Total funding: $120000 (United States dollar) Funding competitive?: Yes, this fund is open to all local and international students Said Foundation Scholarship 2006/9 - 2007/8 University of Strathclyde-UK Funding source: Said Foundation, 24 Queen Anne's Gate, London, SW1H 9AA, United Kingdom Total funding: $30000 (United States dollar) Funding competitive?: Yes, this fund is open to all applicants from Syria, Lebanon, Jordan, Iraq, and Palestine ________________________________________________________________________________ Page 4 of 7 ________________________________________________________________________________ PROFESSIONAL MEMBERSHIPS Professional Affiliations Pharmacy Practicing License (Ministry of Health -Palestine- Reg. #: 13/46) Pharmacy Practicing License (Pharmaceutical Association - Jerusalem Centre - Reg. #: 1333) American Chemical Society ________________________________________________________________________________ SKILLS Languages Fluent English and Arabic. Computer skills (software) GCQ (Thermo), LCQ-classic (Thermo), LCQ-Deca (Thermo), Xcalibur, Origin 7, Origin pro, Sigma plot, Minitab, SIMCA, Microsoft office , ChemDraw, Molecular Modeling packages (Amber, Sybyl 6.3, Mardigras, Discovery Studio, PyMOL), Sparky , Topspin and various NMR packages. Familiarity with online database searching (e.g. Web of Science, Crossfire, SciFinder, PubMed) and Chemical Abstracts. I am licensed to use the UK National Grid Service (NGS). ________________________________________________________________________________ AWARDS RECEIVED Distinguished Scholar Award-Arab Fund for Social and Academic Development (2013-2014) Visiting Professor, Leslie Dan Faculty of Pharmacy-University of Toronto. Canada. University of Strathclyde Research Scholarship (2007-2010)-PhD. in Pharmacy and Biomedical Sciences, University of Strathclyde. UK. Said Foundation Scholarship (2006-2007) - MSc. in Pharmaceutical Analysis, University of Strathclyde. UNRWA University Scholarship (1996-2001) - BSc. in Pharmacy, An-Najah National University. _______________________________________________________________________________________ PUPLICATIONS Articles published in refereed journals: Thiazotropsin aggregation and its relationship to molecular recognition in the DNA minor groove. Marie-Virginie Salvia, Fiona Addison, Hasan Y Alniss, Niklaas J Buurma, Abedawn I Khalaf, Simon P Mackay, Nahoum G Anthony, Colin J Suckling, Maxim P Evstigneev, Adrián Hernandez Santiago, Roger D Waigh, John A Parkinson. Biophysical Chemistry. 2013, 179, 1–11. Rationalizing sequence selection by ligand assemblies in the DNA minor groove: the case for thiazotropsin A. Hasan Y. Alniss, Nahoum G. Anthony, Abedawn I. Khalaf, Simon P. Mackay, Colin J. Suckling, Roger D. Waigh, Nial J. Wheate and John A. Parkinson. Chem. Sci., 2012, 3, 711-722 _______________________________________________________________________________________ Page 5 of 7 _______________________________________________________________________________________ Ranking ligand affinity for the DNA minor groove by experiment and simulation. Wittayanarakul K, Anthony NG, Treesuwan W, Hannongbua S, Alniss H, Khalaf AI, Suckling CJ, Parkinson JA and MacKay SP. Med. Chem. Lett. Med. Chem. Lett., 2010, 1 (8), 376–380. A detailed binding free energy study of 2:1 ligand-DNA complex formation by experiment and simulation. Treesuwan W, Wittayanarakul K, Anthony NG, Huchet G, Alniss H, Hannongbua S, Khalaf AI, Suckling CJ, Parkinson JA and Mackay SP Physical Chemistry Chemical Physics, 2009, 11, 10682-10693. Molecular recognition of DNA by thiazotropsin class analogues through the DNA minor groove. Hasan Y. Alniss, Stephanie A. T. Dillon, Nahoum G. Anthony, Abedawn I. Khalaf, Simon P. MacKay, Colin J. Suckling and John A. Parkinson. (Submitted to the journal Chemistry: A European Journal, 2014) Posters: Hasan Y. Alniss, Nahoum G. Anthony, John A. Parkinson, Simon P. MacKay. Thermodynamics of Lexitropsins-DNA interactions. Biomedicinal Chemistry and Drug Discovery (BCDD) Research Day. SIPBS, Glasgow.UK. June 16, 2008. Hasan Y. Alniss, Marie-Virginie Salvia & John A. Parkinson. A Sticky Problem: Harnessing selfassembly for DNA molecular recognition. Physical Organic Chemistry Symposium. Glasgow, UK. April 7- April 9, 2009. Hasan Y. Alniss, Nahoum G. Anthony, John A. Parkinson, Simon P. MacKay. Investigating the processes that drive lexitropsins-DNA associations. Biomedicinal Chemistry and Drug Discovery (BCDD) Research Day. SIPBS, Glasgow.UK. June 15, 2009. _______________________________________________________________________________________ Presentations: Thermodynamics of lexitropsin-DNA interactions. Faculty Research Seminar Series, Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, UK. March 19, 2008. Molecular modelling of ligand-DNA complexes Faculty Research Seminar Series, Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, UK. August 13, 2008. Using NMR spectroscopy to obtain 3D structures of ligand-DNA complexes Faculty Research Seminar Series, Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, UK. August 19, 2009. Biophysical characterisation of the processes that drive ligand association with the minor groove of DNA Faculty Research Seminar Series, Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, UK. June 16, 2010. _______________________________________________________________________________________ Page 6 of 7 _______________________________________________________________________________________ REFEREES Prof Simon P. Mackay University of Strathclyde, SIPBS, 27 Taylor Street, Glasgow G4 0NR, UK Tel: +44(0)141 548 2866 Email: [email protected]. Dr John A. Parkinson University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL,UK Tel: +44 (0)141 548 2820 Email: [email protected] Prof Rob Macgregor University of Toronto, Leslie Dan Faculty of Pharmacy, 144 College Street, Toronto, Ontario, M5S 3M2, Canada Tel: 001 416-978-7332 Email: [email protected] Dr Nial Wheate Faculty of Pharmacy, University of Sydney, Pharmacy Building (A15) Sydney NSW, Australia Tel: +61 (0)2 9036 7647 Email: [email protected] _______________________________________________________________________________________ Page 7 of 7