Dr Lenka Munoz

Associate Lecturer, Faculty of Pharmacy

Qualifications

MPharm, PharmD, PhD

Contact Details

University of Sydney
Phone: +61 2 9351 8582
Fax: +61 2 9351 4391
Email:
Room S303
Pharmacy Building A15
The University of Sydney
NSW 2006 Australia

Career profile

Dr Munoz completed both her Master of Pharmacy (graduated summa cum laude) and PharmD studies through the Comenius University in Bratislava, Slovakia. During this period she was awarded CIMO Bilateral Scholarship to undertake part of her PharmD research at the University of Helsinki, Finland.

Dr Munoz obtained her PhD in Medicinal Chemistry from the University of Bonn, Germany. The successful research on neuronal nicotinic acetylcholine receptors (nAChRs) was recognized with travel awards by The Parkinson Institute (Sunnyvale, USA) and the GlaxoSmithKline Stiftung (Munich, Germany). These awards enabled the presentation of her work at internationally renowned meetings such as the Annual Meeting of Society for Neuroscience (2003) and the US National Medicinal Chemistry Symposium (2004). By developing structure-activity relationship profiles of nAChRs agents, she was able to design a number of novel and selective nAChRs receptor ligands, leading to 2 peer-reviewed publications and an international patent, filed in January 2007 (in collaboration with Yale University, New Haven, USA).

After her graduation in Nov 2005 she went on to a postdoctoral position at the prestigious Northwestern University in Chicago, USA, supported by a fellowship from Northwestern University’s Center for Drug Discovery and Chemical Biology. As a member of an integrative chemical biology team, Dr Munoz participated in the development and IND filing of a novel therapeutic agent for treatment of neurodegenerative disorders - Minozac – which is currently in the clinical development, entering Phase I clinical trials later this year.

Furthermore, Dr Munoz’s post-doctoral research in the field of p38 MAPK inhibitors greatly contributed to the drug discovery and rational drug design of molecules for treatment of Alzheimer’s and other neurodegenerative diseases. Discovery of compounds directed towards signaling molecules such as p38 MAPK, which are important in a number of mechanisms that go awry in neurodegenerative disorders, is of great importance at this time when such disorders plague our growing aging population. Her latest publication provides in-vivo evidence that the brain p38α MAPK is a viable molecular target for future development of potential disease-modifying therapeutics in AD and related neurodegenerative disorders.

The opportunity to teach at the leading Australian university and to establish her own research group played a major part in Dr Munoz’s decision to leave her challenging postdoctoral work at the Northwestern University. Dr Munoz was appointed Associate Lecturer in Pharmaceutical Chemistry at the University of Sydney in April 2007.

Research Interests

In the modern history of drug discovery, the G-protein coupled receptors have played the diva’s role – center stage with top billing. Meanwhile, evidence mounts that there are other equally important players in the drug discovery – e.g. protein family called PROTEIN KINASES, which represent critical components of cellular signal transduction cascades. They are directly involved in many diseases, including cancer, diabetes and inflammation. The approval of imatinib (Gleevec) for chronic myeloid leukemia, together with another eight FDA approved kinase inhibitors, has provided the proof-of-principle that small molecule kinase inhibitors can be effective drugs.

The MITOGEN-ACTIVATED PROTEIN KINASES (MAPKs) play a central role in the regulation of most biological processes including cell growth, proliferation, differentiation, inflammatory responses and programmed cell death. The three major MAP signaling proteins consist of the extracellular signal-regulated kinases (Erk), c-Jun N-terminal kinases (JNK) and p38 MAP kinases. Unregulated activation of these MAP kinases is involved in inflammatory diseases, neurodegeneration and cancer cell proliferation.

Our research interest lies in identifying and developing novel and specific MAP kinase inhibitors that may find utility as chemotherapy, anti-inflammatory or anti-neurodegenerative agents. Through a dynamic integration of structural biology, biological mechanisms and pathways, rational drug design and chemistry space, the research is aimed at rapid and “smart” DRUG DISCOVERY of small-molecule kinase inhibitors and development of promising clinical candidates.

The “smart” drug discovery platform is being developed in close collaboration with Dr. Alaina Ammit and Dr. Bret Church (The University of Sydney) and Prof. Stefan Laufer (University of Tübingen, Germany).

Recent Publications

• Munoz L., Ralay Ranaivo H., Roy S.M., Hu W., Craft J.M., McNamara L.K., Wing Chico L., Van Eldik L.J. and Watterson D.M. A Novel p38 MAPK Inhibitor Suppresses Brain Proinflammatory Cytokine Up-Regulation and Attenuates Synaptic Dysfunction and Behavioral Deficits in an Alzheimer's Disease Mouse Model, J Neuroinflammation, in press.
• Hu W., Ralay Ranaivo H., Roy S.M., Behanna H.A., Wing L.K., Munoz L., Guo L., Van Eldik L.J. and Watterson D.M. Development of a Novel Therapeutic Suppressor of Brain Proinflammatory Cytokine Up-regulation that Attenuates Synaptic Dysfunction and Behavioral Deficits. Bioorg Med Chem Lett 17 (2007) 414 – 418
• Munoz, L.; Abdelrahman, A.; Fleischer, R.; Weigt, M.; Wiese, M.; Gündisch, D. Microwave-Assisted Synthesis of Cytisine Derivatives and Evaluation as Ligands for Nicotinic Acetylcholine Receptors, Medicinal Chemistry, submitted (publication held due patent pending)
• Gündisch D, Andrä M, Munoz L., Tilotta C.M.: Synthesis and Evaluation of Phenylcarbamate Derivatives as Ligands for Nicotinic Acetylcholine Receptors. Bioorg Med Chem 12 (2004) 4953 – 4962.
• Gyűrösiová L. (maiden name), Sedlárová E., Čizmárik J.: [[i|Study of Local Anaesthetics, Part 156: Some Physicochemical and Lipophilic Properties of o-, m-, p- Alkoxysubstituted Pyrrolidinoethylesters of Phenylcarbamic Acid.]] Chemical Papers 56 (2002) 340-344.
• Gyűrösiová L. (maiden name), Laitinen L., Raiman J., Čizmárik J., Sedlárová E., Hirvonen J.: Permeability Profiles of m-Alkoxysubstituted Pyrrolidinoethylesters of Phenylcarbamic Acid across Caco-2 Monolayers and Human Skin. Pharm Res 19 (2002) 162-169