Maija DAMBROVA
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
Research experience
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
Honors and Awards
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. Zeltin, Dr. A. Leonciks, Dr. A. Kazaks, J. Rumnieks,
S. Kotelovica, J. aripo, LZA cor. memb. M. Dambrova, Dr. E. Liepin, J. Kuka,
Acad. E. Liepin, 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 Kalvin, LZA cor. memb. Maija Dambrova, Edgars Liepin, Osvalds Pugovics,
Einars Loa; Latvian Institute of Organic Synthesis)
2009 Silver
and Bronze prizes in Korea International Womens 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
Teaching experience
- 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. Liepin, 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.
Head of Research projects
- 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
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.
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
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
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
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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.
Muceniece
R, Dambrova M. Melanocortins in brain inflammation: the role of melanocortin
receptor subtypes. Adv Exp Med Biol., 2010;681:61-70.
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.
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): 455460.
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.
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.
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.
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, 387394.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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
Schmiedebergs Arch. Pharmacol. 2004; 369: 533-539.
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.
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.
Dambrova M., Liepinsh E., Kalvinsh I., Mildronate.
Cardioprotective Action through Carnitine-Lowering Effect, Trends Cardiovasc. Med.
2002; 12: 275-279.
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.
Patent applications
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., Kalvin
I., Vilskersts R., Liepin 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., Kalvin 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