Maija DAMBROVA Head of the Laboratory of Pharmacology, Department of Medicinal Chemistry Latvian Institute of Organic Synthesis, Aizkraukles iela 21, Riga, LV-1006 Latvia Phone/Fax: +371 67702408 E-mail: [email protected]

Date and place of birth: May 3, 1968, Gulbene, Latvia

Fluent in: Latvian (native), English, Russian, and Swedish.

Research interests and activities

    Pharmacology, molecular mechanisms and medicinal chemistry related to the anti-ischemic drugs with novel mechanisms of action, cellular energy metabolism, and inflammation.

    58 SCI publications, 12 patents.
    Presentations at more than 50 international meetings.

Education

2004                  MBA, Riga International School of Economics and Business Administration.
                         Thesis: “Pharmacoeconomics in Latvia”

2001                 Dr. pharm., University of Latvia, Riga, Latvia

1999                 PhD in Pharmaceutical Pharmacology, Uppsala University, Uppsala, Sweden
                          Thesis: „Discovery of N-hydroxyguanidines as novel electron acceptors of xanthine oxidase. Potential new drugs for treatment of ischaemia and reperfusion injury”

1993                  Master degree in Biology, University of Latvia, Faculty of Biology, Riga, Latvia

2005                 Head of Laboratory of Pharmaceutical Pharmacology, Medicinal Chemistry Department, Latvian Institute of Organic Synthesis, Riga, Latvia

2001                  Leading researcher, Latvian Institute of Organic Synthesis, Riga, Latvia                      

1999                  Research scientist, Medicinal Chemistry Department, Latvian Institute of Organic Synthesis, Riga, Latvia

1995-1999        Ph.D. student in Pharmaceutical Pharmacology, Uppsala University, Department of Pharmaceutical
                          Biosciences, Uppsala, Sweden

1995                 Postgraduate exchange student, Department of Pharmaceutical Biosciences, Division of Pharmacology,
                         Uppsala Biomedical Centre, Sweden (Swedish Institute stipend)

1994                 Postgraduate exchange student, Department of Pharmacology and Toxicology, University of Kuopio, Finland (CIMO stipend from
                        Nordic    Council)

1993(3 months) Postgraduate exchange student, Institut fur Biochemie und Molekularbiologie, University of Bern, Switzerland

1991                 Assistant, Laboratory of Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia

Specialized courses

• Baltic SUMMER School, 2002, “Signalling in Muscle Metabolism”, Copenhagen
• VIIth LACDR School on Medicinal Chemistry, 1998, Noordwijkerhout, the Netherlands (Travel grants from European University Consortium for Pharmaceutical Research  /ULLA/ and Swedish Medical Research Council)
• NorFA-sponsored lecture course “Molecular Biology and Pharmacology of Receptors”, 1994, Turku, Finland

• 2011   S. Hiller Medal (Latvian Institute of Organic Synthesis) for the achievements in innovative drug research
• 2010    Listed in the top ten scientific developments in Latvia in scientific research: Characterization of 3-D structure of enzyme g-butyrobetaine hydroxylase, which will aid the discovery of novel cardioprotective drugs (LZA cor. memb. K. Tars, Dr. A. Zeltinš, Dr. A. Leonciks, Dr. A. Kazaks, J. Rumnieks, S. Kotelovica, J. Šaripo, LZA cor. memb. M. Dambrova, Dr. E. Liepinš, J. Kuka, Acad. E. Liepinš, K. Jaudzems, Prof. A. Viksna, Latvian Biomedical Research and Study Centre, Latvian Institute of Organic Synthesis, University of Latvia)
• 2009    Listed in the top ten scientific developments in Latvia in scientific research: Discovery of novel cardioprotective drug that is 40-fold more active than mildronate (akad. Ivars Kalvinš, LZA cor. memb. Maija Dambrova, Edgars Liepinš, Osvalds Pugovics, Einars Loža; Latvian Institute of Organic Synthesis)
• 2009    Silver and Bronze prizes in Korea International Women’s Invention Exposition (KIWIE2009) for investigations of different pharmacological activities of optic isomers and new method for regulation of cellular energy metabolism
• 2008    European Federation of Pharmaceutical Industries and Associations (EFPIA) nomination “Portraits of Science – Scientists of Tomorrow”
• 2008    Listed in the top ten scientific developments in Latvia in scientific research: “Approaches for the synthesis and isolation of pure optical isomers of biologically active compounds were developed and their properties studied; these findings contribute to developing more effective medications”, The Latvian Institute of Organic Synthesis - Professor I. Kalvins, Dr.habil.chem. E. Lukevics, Dr.pharm. M. Dambrova, Dr.chem. A. Krauze, Dr.habil.chem. G. Veinberg.
• 2007   Elected Corresponding Member of Latvian Academy of Sciences
• 2004    D.H. Grindel medal for investigations of mechanism of action of cardioprotective drug mildronate
• 2006    L`Oréal Latvian fellowship "For Women in Science" with the support of the Latvian National Commission for UNESCO and the Latvian Academy of Sciences
• 2000    Young Scientist Travel Award, Millennial World Congress of Pharmaceutical Sciences, San Francisco, USA

Organizing activities

• Member of the Latvian Biochemical Society
• Member of the Latvian Pharmacological Society
• Member of the European Associationfor the Study of Diabetes (EASD)
• Member of the Latvian Council of Genetically modified organism and novel food supervision, Latvian Food Centre, 2002-2006
• Member of the Programme Committee for Research Infrastructures, FP6, European Commission , 2002-2004
• Member of the Scientific Advisory Committee, the DG Joint Research Centre, the European Centre for the Validation of Alternative Methods (Institute for Health and Consumer Protection), 2003 - 2009
• Member of the Programme Committee for the FP7 specufic Programme "Cooperation". Theme 1 Health, European Comission, 2008 - 2010
• Member of the Scientific Advisory Board for Genetically modified organisms, Latvian Food Centre, Food and Veterinary Service, 2009 -
• Member of Expert Committee of Biological and Medical Sciences, Latvian Council of Science, 2010 - 2014
• Member in the intergovernmental framework for European Cooperation in Science and Technology (COST), domain committee for Biomedicine and Molecular Biosciences, 2010 - 2014

• Associated Professor, Riga Stradins University, Faculty of Pharmacy (2011)
• Lecture course: “Use of radioligands and radioactivity in medicine”, Faculty of Medicine, University of Latvia.
• Supervisor of 3 PhD theses (Dr.pharm. E. Liepinš, 2005; Dr.pharm. R.Vilskersts, 2009, University of Latvia; Dr.pharm. Janis Kuka, 2011, Riga Stradins University), scientific consultant ( Dr.med.  I.Konrade, 2008, Riga Stradins University). Oponent of PhD thesis: Dr. B.Jansone, University of Latvia, 2005; Dr.A. Uustare, Tartu University, Estonia, 2006; Dr. A. Vonk, Tartu University, Estonia, 2009. P    
• Supervisor and oponent for B.Sc. and M.Sc. thesis, Faculty of Biology and Faculty of Medicine, University of Latvia.

• European Regional Development Fund (ERDF), activity 2.1.1.1. project 2DP/2.1.1.1.0/10/APIA/VIAA/059 "The synthesis and investigation of biological activity of novel nootropic drugs" (2010 - 2013).
• Latvian State research program „The development of new prophylactic, treatment and diagnostic means and methods for improved public health” subproject „Investigations of diabetic complications and biological activity of cardiovascular drugs”,Co-head     (2010-2013).
• European Foundation for the Study of Diabetes (EFSD) grant programm New Horizons Collaborative Research Initiative project „Metabolomic analysis of diabetes: elucidating the metabolic correlates of diabetic complications” (in collaboration with Glazgow University, UK) (2010-2011).
• The European Economic Area (EEA) Financial Mechanism, Academic research block grant project NR. EEZ09AP-57  Investigation of novel molecular markers of the late complications of diabetes mellitus   (2009-2010).
• Latvian   State research program „New drugs and biocorrectors: constructing, forms of transport and mechanisms of action”; sub-project: New therapies and molecular mechanisms of drugs in CNS and cardiovascular pharmacology (2005-2009).
• European Regional Development Fund (ERDF), priority „Promotion of entrepreneurship and innovations”, grant for applied science project „Identification of biomarker complex in metabolome of heart diseases” (2006-2008).
• Latvian Council of Science grant 05.1461: The role of carnitine biosynthesis in regulation of heart energy metabolism and treatment of ischaemic heart disease (2005-2008).
• Reserch grant in collaboration with JSC Grindeks: Scientific research  of pharmacological activities of Mildronate (2005 - 2006).
• Applied research project (Ministry of Education and Science of Republic of Latvia): Synthesis, toxicity and bioavailability profile of mildronate salts (2004-2005).
• Applied research project (Ministry of Education and Science of Republic of Latvia): Development of Xilometazoline containing gel for rhinitis treatment (2003-2004).
• Grant of Taiho Latvija Foundation: Molecular mechanisms of action of antiischemic compounds (2003-2005.
• Latvian Council of Science grant 01.0209: Novel type of xanthine oxidase inhibitors-electron acceptors as potential new drugs for treatment of ischemia and reperfusion injury (2001-2003).

Representative publications

1. Konrade I, Dambrova M, Makrecka M, Neimane L, Strele I, Liepinsh E, Lejnieks A, Vevere P, Gruntmanis U, Pirags V. Seasonal iodine deficiency in Latvian school children, Thyroid, 2012, 22(10): 1088-1089.
2. Skapare E, Konrade I, Liepinsh E, Makrecka M, Zvejniece L, Svalbe B, Vilskersts R, Dambrova M. Glyoxalase 1 and glyoxalase 2 activities in blood and neuronal tissue samples from experimental animal models of obesity and type 2 diabetes mellitus, The Journal of Physiological Sciences, 2012, DOI: 10.1007/s12576-012-0224-9
3. Vorona M.,Veinberg G., Vikainis S., Kuznetsov E., Lebedev A., Ponomarev Yu., Chernobrovijs A., Zvejniece L., Dambrova M. Novel methods for synthesis of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide ((R)-Phenotropil). Chem.Heterocycl. Comp. (Engl. Ed.). 2012, 48(5). (Rus. Ed.) 2012, 5(539), 775-778
4.    Kuka J, Makrecka M, Grinberga S, Pugovics O, Liepinsh E, Dambrova M. A short-term high-dose administration of sodium pivalate impairs pyruvate metabolism without affecting cardiac function. Cardiovascular Toxicology, 2012, in press, DOI: 10.1007/s12012-012-9169-8
5.   Zvejniece L, Svalbe B, Liepinsh E, Pulks E, Dambrova M. Sensorimotor and cognitive deficits in rats following 90- or 120-min transient occlusion of the middle cerebral artery, Journal of Neuroscience Methods, 2012, 208(2):197-204.
6. Liepinsh E., Skapare E., Vavers E., Konrade I., Strele I., Grinberga S., Pugovics O., Dambrova M. High l-carnitine concentrations do not prevent late diabetic complications in type 1 and 2 diabetic patients. Nutrition Research, 2012, 32:320-327 3.
7.    Vilskersts R, Vigante B, Neidere Z, Krauze A, Domracheva I, Bekere L,. Shestakova I, Duburs G, Dambrova M, Calcium Level Controlling Activities of Novel Derivatives of Amlodipine, Riodipine and Cerebrocrast, Letters in Drug Design & Discovery, 2012, 9(3):322-328
8.    Kuka J, Vilskersts R, Cirule H, Makrecka M, Pugovics O, Kalvinsh I, Dambrova M, Liepinsh E, The cardioprotective effect of mildronate is diminished after co-treatment with L-carnitine, Journal of Cardiovascular Pharmacology and Therapeutics, 2012, 17(2):215-22. doi:10.1177/107424841 1419502
9.   Liepinsh E, Konrade I, Skapare E, Pugovics O, Grinberga S, Kuka J, Kalvinsh I, Dambrova M, Mildronate treatment alters gamma-butyrobetaine and L-carnitine concentrations in healthy volunteers, Journal of Pharmacy and Pharmacology, 2011, 63(9):1195-1201.
10.    Zvejniece L, Svalbe B, Veinberg G, Grinberga S, Vorona M, Kalvinsh I, Dambrova M, Investigation of stereoselective pharmacological activity of phenotropil, Basic & Clinical Pharmacology & Toxicology, 2011;109(5):407-12.
11.   Vilskersts R, Kuka J, Svalbe B, Cirule H, Liepinsh E, Grinberga S, Kalvinsh I, Dambrova M, Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats, Pharmacological reports, 2011, 63(3):752-762.
12.   Skapare E, Riekstina U, Liepinsh E, Konrade I, Makrecka M, Maurina B, Dambrova M, Flow cytometric analysis of glyoxalase-1 expression in human leukocytes, Cell Biochemistry and Function, 2011, 29(2):171-174.
13. Liepinsh E, Skapare E, Svalbe B, Makrecka M, Cirule H, Dambrova M, Anti-diabetic effects of mildronate alone or in combination with metformin in obese Zucker rats, European Journal of Pharmacology, 2011, 658(2-3):277-283.  
14. Svalbe B, Zvejniece L, Vavers E, Pugovichs O, Muceniece R, Liepinsh E, Dambrova M, Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats, Behavioural Brain Research, 2011, 222(1):26-32.
15.    Tars K, Rumnieks J, Zeltins A, Kazaks A, Kotelovica S, Leonciks A, Saripo J, Viksna A, Kuka J, Liepinsh E, Dambrova M, Crystal Structure of Human gamma-Butyrobetaine Hydroxylase, Biochem. Biophys. Res. Commun., 2010, 398(4):634-639.
16.   Muceniece R, Dambrova M. Melanocortins in brain inflammation: the role of melanocortin receptor subtypes. Adv Exp Med Biol., 2010;681:61-70.
17.    Zvejniece L, Svalbe B, Makrecka M, Liepinsh E, Kalvinsh I, Dambrova M, Mildronate exerts acute anticonvulsant and antihypnotic effects, Behavioral Pharmacology, 2010, 21(5-6):548-55.
18. Dambrova M, Zvejniece L, Skapare E, Vilskersts R, Svalbe B, Baumane L, Muceniece R, Liepinsh E, The anti-inflammatory and antinociceptive effects of NF-?B inhibitory guanidine derivative ME10092, Int. J. Immunopharmacol., 2010; 10(4): 455–460.
19.   Jaudzems K, Kuka J, Gutsaits A, Zinovjevs K, Kalvinsh I, Liepinsh E, Liepinsh E, Dambrova M. Inhibition of carnitine acetyltransferase by mildronate, a regulator of energy metabolism, Journal of Enzyme Inhibition and Medicinal Chemistry, 2009, 24,1269-1275.
20. Vilskersts R, Liepinsh E, Mateuszuk L, Grinberga S, Kalvinsh I, Chlopicki S, Dambrova M.  Mildronate, a Regulator of Energy Metabolism, Reduces Atherosclerosis in apoE/LDLR Mice, Pharmacology, 2009, 83(5): 287-293.
21. Liepinsh E, Vilskersts R, Zvejniece L, Svalbe B, Skapare E, Kuka J, Cirule H, Grinberga S, Kalvinsh I, Dambrova M. Protective effects of mildronate in an experimental model of type 2 diabetes in Goto-Kakizaki rats. Br. J. Pharmacol. 2009, 157(8), 1549-1556.
22. Liepinsh E, Kuka J, Svalbe B, Vilskersts R, Skapare E, Cirule H, Pugovics O, Kalvinsh I, Dambrova M, Effects of Long-Term mildronate treatment on cardiac and liver functions in rats, Basic & Clinical Pharmacology & Toxicology, 2009, 105, 387–394.
23. Jankevics A, Liepinsh E, Liepinsh E, Vilskersts R, Grinberga S, Pugovics O, Dambrova M.  Metabolomic studies of experimental diabetic urine samples by 'H-NMR spectroscopy and LC/MS method, Chemom. Intellig. Lab. Syst., 2009, 97(1): 11-17.
24. Teus M., Jirgensons A., Dambrova M., Mezhapuke R., Parsons C.G., Danysz W. Identification of GCP II Inhibitors Based on 4-Arylmethyl-3-(carboxyphenyl)-5-hydroxyisoxazole Scaffold, Letters in Drug Design & Discovery, 2009, 6(1): 29-32.
25. Jankevics A, Liepinsh E, Liepinsh E, Vilskersts R, Grinberga S, Pugovics O, Dambrova M, Metabolomic studies of experimental diabetic urine samples by ¹H NMR spectroscopy and LC/MS method, Chemom. Intellig. Lab. Syst., 2009, 97(1): 11-17.
26. Vilskersts R, Liepinsh E, Mateuszuk L, Grinberga S, Kalvinsh I, Chlopicki, Dambrova M. Mildronate, a regulator of energy metabolism, reduces atherosclerosis in apoE/LDLR^-/- mice. Pharmacology, 2009, 83(5), P.287-293.
27. Vilskersts R, Liepinsh E, Kuka J, Cirule H, Veveris M, Kalvinsh I, Dambrova M, Myocardial infarct size-limiting and anti-arrhythmic effects of mildronate orotate in the rat heart, Cardiovascular Drugs & Therapy, 2009, V23(4), P.281-288.
28. Teus M., Jirgensons A., Dambrova M., Mezhapuke R., Parsons C. G., Danysz W. Identification of GCP II Inhibitors Based on 4-Arylmethyl-3-(4- carboxyphenyl)-5-hydroxyisoxazole Scaffold. Letters in Drug Design & Discovery, 2009, 6(1): 29-32.
29. Liepinsh E, Vilskersts R, Skapare E, Svalbe B, Kuka J, Cirule H, Pugovics O, Kalvinsh I, Dambrova M. Mildronate decreases carnitine availability and up-regulates glucose uptake and related gene expression in the mouse heart, Life Sciences, 2008, V(83): 613-619.
30. Grinberga S, Zvejniece L, Liepinsh E, Dambrova M, Pugovics O. Quantitative analysis of phenibut in rat brain tissue extracts by liquid chromatography-tandem mass spectrometry, Biomedical Chromatography, 2008, 22(12): 1321-1324.
31. Muceniece R., Saleniece K., Krigere L., Rumaks J., Dzirkale Z., Mezhapuke R., Kviesis J., Mekss P., Klusa V., Sciöth H.B., Dambrova M. Potato (Solanum tuberosum) Juice Exerts an Anticonvulsant Effect in Mice through Binding to GABA receptors, Planta Med., 2008, 74(5): 491-496.
32. Dambrova M,  Zvejniece L, Liepinsh E, Cirule H, Zharkova O, Veinberg G, Kalvinsh I. Comparative pharmacological activity of optical isomers of phenibut, Eur. J.Pharmacol., 2008, 583(1): 128-134.
33. Liepinsh E, Vilskersts R, Skapare E, Svalbe B, Kuka J, Cirule H, Pugovics O, Kalvinsh I, Dambrova M, Mildronate decreases carnitine availability and up-regulates glucose uptake and related gene expression in the mouse heart, Life Sciences, 2008, V(83), P.613-619.
34. Dambrova M, Cirule H, Svalbe B, Zvejniece L, Pugovichs O, Zorenko T, Kalvinsh I, Liepinsh E, Belozertseva I.  Effect of inhibiting carnitine biosynthesis on male rat sexual performance, Physiology & Behavior, 2008, V 95: 341-347. 
35. Muceniece R., Zvejniece L., Vilskersts R., Liepinsh E., Baumane L., Kalvinsh I., Wikberg J.E., Dambrova M. Functional evaluation of THIQ, a melanocortin 4 receptor agonist, in models of  food intake and inflammation, Basic Clin. Pharmacol. Toxicol., 2007, V101(6): 416-420.
36. Liepinsh E, Vilskersts R, Loca D, Kirjanova O, Pugovichs O, Kalvinsh I, Dambrova M. Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction. J. Cardiovasc. Pharmacol. 2006;48(6):314-319.
37. Muceniece R., Zvejniece L., Kirjanova O., Liepinsh E., Krigere L., Vilskersts R., Baumane L., Gordjusina V.,  Kalvinsh I., Wikberg J.E., Dambrova M. ß-MSH inhibits brain inflammation via MC(3)/(4) receptors and impaired NF-kappaB   signalling, J.Neuroimmunol., 2005, 169: 13-19
38. Dambrova M., Chlopicki S., Liepinsh E., Kirjanova O., Gorshkova O., Kozlovski V., Uhlen S., Liepina I., Petrovska R., Kalvinsh I., The methylester of gamma-butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation, Naunyn Schmiedeberg’s Arch. Pharmacol. 2004; 369: 533-539.
39. Prusis P., Dambrova M., Andrianov V., Rozhkov E., Semenikhina V., Piskunova I., Ongwae E., Lundstedt T., Kalvinsh I., Wikberg J.E., Synthesis and quantitative structure-activity relationship of hydrazones of N-amino-N'-hydroxyguanidine as electron acceptors for xanthine oxidase, J. Med. Chem. 2004; 47:3105-3110.
40. Muceniece R., Zvejniece L., Kirjanova O., Liepinsh E., Krigere L., Baumane L., Kalvinsh I., Wikberg JE., Dambrova M., ß- and ?-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain, Brain Res. 2004; 995(1):7-13.
41. Dambrova M., Liepinsh E., Kalvinsh I., Mildronate. Cardioprotective Action through Carnitine-Lowering Effect, Trends Cardiovasc. Med. 2002; 12: 275-279.
42. Dambrova M, Baumane L, Kalvinsh I, Wikberg JE. Improved method for EPR detection of DEPMPO-superoxide radicals by liquid nitrogen freezing, Biochem. Biophys. Res. Commun., 2000, 275(3): 895-898.

1.    Kalvins I., Lebedevs A., Cernobrovijs A., Dambrova M., Zvejniece L., Vorona M., Veinbergs G. 4R,5S-enantiomer of 2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide with nootropic activity. WO 2011054888, 2011-05-12.

2.  Kalvins I., Dambrova M., Liepins E., Pugovics O., Vilskersts R., Kuka J., Grinberga S., Loza E. Use of 4-[ethyl(dimethyl)ammonio]butanoate in the treatment of cardiovascular disease. WO 2011048201, 2011-04-28.

3.    Kalvins I., Stonans I., Vilskersts R., Liepins E., Dambrova M., Birmans A.    3-(2,2,2-Trimethylhydrazinium) propionate salts for treating myocardial infarction. WO 2009071586, EP 2222376, 2010-09-01.

4.    Kalvins I., Vilskersts R., Liepins E., Dambrova M., Birmans A., Stonans I. Medical use of 3-(2,2,2-trimethylhydrazinium) propionate hydrogen fumarate. EP 2067474, 2009-06-10.

5.       Stonans I., Kalvinš I., Vilskersts R., Liepinš E., Dambrova M. Medical use of 3-(2,2,2-trimethylhydrazinium) propionate orotate. WO2009074498, 2009-06-18.

6.    Veinberg G., Vorona M., Zvejniece L., Chernobrovijs A., Kalvinsh I., Karina L., Dambrova M. N-carbamoylmethil-4(R)-phenil-2-pyrrolidinone, method of its preparation and pharmaceutical use. EP2013166, 2009-01-14. LT2008075, 2009-06-25.

7.    Veinbergs G., Vorona M., Dambrova M., Karina L., Zvejniece L., Kalvinš I., Cernobrovijs A. Method of preparation and use of pharmacologically active N-carbamoylmethyl-4(R)-phenyl-2-pyrolidinone. Pat. WO2007104780, 2007-09-20.

Last update 11.10.2012