Staff
| Personal Information | ||
| Name | Meegan, Mary Jane | |
| College Address | Pharmacy and Pharmaceutical Sciences, East End Development 4/5 |
|
| Main Department | School of Pharmacy | |
| College Title | Professor | |
| mmeegan@tcd.ie | ||
| College Tel | +353 1 896 2798 | |
| Biography | |
| Mary J Meegan completed her PhD degree in UCD in 1976 under the direction of Professor Dervilla Donnelly in the area of natural product chemistry and subsequently carried out postdoctoral research at the University Chemical Laboratory, Cambridge University in the research group of Professor Alan Battersby in the area of porphyrin synthesis and biosynthesis. Following further research periods at University College Dubin and CNRS Gif-sur-Yvette, she was appointed as lecturer in Pharmaceutical Chemistry in 1978 at the School of Pharmacy in Trinity College Dublin. She now has 25 years research experience in the School of Pharmacy , Trinity College in the general area of pharmaceutical and medicinal chemistry , with over 50 peer-reviewed scientific papers covering topics such as design and synthesis of anticancer drugs, drug impurity profiling, synthetic methods for library design and in vitro screening. She has extensive experience in scientific and technical management having led an active research group,( current research group consists of 5 postgraduate students and 2 postdoctoral research fellows) has acted as Head of the Department of Pharmaceutical Chemistry for a 6 year period and is currently acting as subject area head of Pharmaceutical Chemistry at the School of Pharmacy.Research collaborations have been established within Trinity College with Dr D Zisterer and Dr D Lloyd in the Biochemistry Department and also with many European research centres including Universities of Regensburg and Siena. Research is currently funded by research grants from Health Research Board and PRTLI(HEA). She is a member of several International Scientific Societies. | |
| Professional Qualifications | |
| Qualification | Institution | Class of Degree | Title of Dissertation | Date Conferred |
| Ph.D., Chemistry | University College Dublin (NUI) | 1976 | ||
| B.Sc., (First Hons), Chemistry | University College Dublin (NUI) | 1973 |
| Representations |
| Details | Date |
| Guest Editor of Current Topics in Medicinal Chemistry | 2005/2006 |
| Administrative Functions | |
| Details | Level | Date From | Date To |
| Head of subject area Pharmaceutical Chemistry, School of Pharmacy, Trinity College Dublin | 2003 | Present | |
| Head of Department of Pharmaceutical Chemistry, School of Pharmacy, Trinity College Dublin | 1997 | 2003 |
| Membership of Professional Institutions, Associations, Societies |
| Details | Date From | Date To |
| Member of the Royal Society of Chemistry | 1977 | Present |
| Member of the American Chemical Society | 1997 | Present |
| Member of the Society of the Chemical Industry Chartered Chemist | 1990 | Present |
| Awards and Honours | |
| Award | Date |
| Royal Commission 1851 Overseas Postdoctoral Fellowship | 1976 |
| Hugh Ryan Gold Medal in Chemistry, University College Dublin | 1973 |
| Education Details | |
| School/College | Date From | Date To |
| University College Dublin | 1969 | 1973 |
| University College Dublin | 1973 | 1976 |
| Languages |
| Language | Skill Reading | Skill Writing | Skill Speaking |
| English | Fluent | Fluent | Fluent |
| Employment Details | |
| Position Held | Job Description | Where | Date From | Date To |
| Senior Lecturer in Pharmaceutical Chemistry | School of Pharmacy, Trinity College Dublin | 1991 | Present | |
| Lecturer in Pharmaceutical Chemistry | School of Pharmacy, Trinity College Dublin | 1979 | 1991 | |
| Postdoctoral Fellow | Department of Chemistry, University College Dublin | 1977 | 1979 | |
| Postdoctoral Fellow | University Chemical Laboratory, Cambridge, UK | 1976 | 1977 | |
| Royal Commission 1851 Overseas Postdoctoral Fellowship | University Chemical Laboratory, Cambridge, UK | 1976 | 1977 |
| Description of Research Interests |
| My research interests lie in Pharmaceutical Chemistry in the rational design of new medicines, specifically in the design of highly potent and selective estrogen receptor modulators (SERMs) which may be utilised in the treatment of breast cancer and osteoporosis. Extensive molecular modelling analysis of the specific interactions between drugs such as tamoxifen and raloxifene and models of the protein target (the Estrogen Receptor) has led to the design and synthesis of novel structurally modified estrogen receptor modulators with altered selectivity and affinity for the protein receptor. Ongoing research is examining the relationship between structure and antiproliferative activity of these products against MCF-7 breast cancer cells, and may lead to a better understanding of the specific structural requirements for estrogen receptor agonist and antagonist activity. This research work is carried out in collaboration with Dr. D. Zisterer and Dr. D. Lloyd in the Department of Biochemistry, Trinity College Dublin. Related research interests include the investigation of the mechanism of action of novel cytotoxic heterocycles against breast cancer cell lines (both ER+ and ER-)and the development of virtual high throughput screening computational methodologies for the identification of new anticancer molecular scaffolds. In addition, we have extensive expertise in the area of impurity profiling of amphetamines and related ecstasy type drugs of abuse and also have established current research projects involving the design and evaluation of novel selective serotonin reuptake inhibitors. |
| Research Interests | |||
| Amphetamines | Anticancer Drug Design | Antiestrogens | Carbapenem antibiotics |
| Chemistry of drug metabolism | Chemistry of drug receptor interactions | Design and synthesis of drugs | Drug development |
| Molecular modelling of Estrogen Receptor antagonists | Pharmacologically active heterocycles |
| Research Projects | |
| Project title | Development of an in silico high-throughput screening system for the estrogen receptor |
| Summary | Before the advent of rational drug design (RDD), new drug candidates were screened randomly and the success rates were extremely low (about 1 in 15 000) thus delaying the provision of new therapeutics. The development of RDD approaches has given researchers the power to design candidate drugs based on the physico-chemical properties of their targets. The output from the human genome project and the technologies of proteomics and structural genomics are now furnishing validated targets for varied disease states. In this project we have developed a suite of computational drug design programs optimised to carry out high throughput in silico screening of candidate compounds on highly parallel computing systems using X-ray crystal or homology models of biological receptors for specific disease states. Initially we have focussed on the development of computational docking algorithms to fit candidate ligands to the estrogen receptors to facilitate our research in the development of therapeutics for use in breast cancer treatment. The efficacy of fit arising from these docking routines is complimented through parallel wet biochemical experimental evaluation of binding affinities for ligands in cloned estrogen receptors using commercially available assay kits. This experimental data has been used to validate the in silico methodology and to provide refinement parameters in the development and optimisation of scoring algorithms. These tools will be applicable in the design of ligands for any pathogenic process wherein a target protein structure is known or may be determined, thus shortening R&D times for the provision of new therapeutics |
| Funding Agency | Health Research Board |
| Programme | Interdisciplinary Research |
| Type of Project | |
| Date from | September 2002 |
| Date to | September 2005 |
| Person Months | 36 |
| Publications |
| Peer Reviewed |
| David G. Lloyd, Helena M. Smith, Andrew S. Knox, Daniela M. Zisterer and Mary J. Meegan, , 1. Flexible Estrogen Receptor Modulators: Synthesis, Biochemistry and Molecular Modeling Studies for 3-Benzyl-4,6-diarylhex-3-ene and 3,4,6-Triarylhex-3-ene Derivatives; , Medicinal Chemistry, 3, 2007, p135 - 155 | |
| Meegan, M.J., , Nuclear Receptors as targets in Drug Discovery: Medicinal and Therapeutic Potential; , Current Topics in Medicinal Chemistry, , 6, , , (3), 2006, p179- |
| Non Peer Reviewed | |
| Jason Horan and Mary J. Meegan, Synthesis and characterisation of 1,2,3,4-tetrahydroisoquinolines:, 2006All Ireland Schools of Pharmacy28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, ppP24- | |
| Cormac A. O’Donohoe, Andrew S. Knox, and Mary J. Meegan, Antiproliferative and physiological stability studies , 2006All Ireland Schools of Pharmacy 28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, ppP14- | |
| Thomas F. Greene, Thomas McCabe, Mary J. Meegan., The â-Lactam Ring as a Scaffold for Combretastatin A-4 Analogues, 2006All Ireland Schools of Pharmacy, 28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, ppP52- | |
| More Publications>>> | |