Markku Kurkinen, 75, PhD, Co-Founder, CEO, CSO, Kurkinen Group
Markku Kurkinen, 74, PhD, Co-Founder, President, CEO, CSO, Kurkinen Group
October 8, 1949, Mikkeli, Finland
Finnish Citizen, Permanent Resident of the USA
1974 MS, University of Helsinki, Finland
1979 PhD, University of Helsinki, Finland (thesis advisor Antti Vaheri)
1980-83 post-doctoral work with Brigid Hogan, Imperial Cancer Research Fund (ICRF), Mill Hill, London, UK
1983-84 EMBO Fellow, State University of New York (SUNY), Stony Brook, New York, USA (with Sid Strickland) and University of Medicine and Dentistry of New Jersey (UMDNJ), Rutgers Medical School, Piscataway, New Jersey, USA (with Darwin J. Prockop)
1984-86 Assistant Professor, UMDNJ (with Darwin J. Prockop)
1986-92 Associate Professor, Chief of Division of Connective Tissue Research, UMDNJ (with Edward D. Harris)
1992-2019 Professor, Wayne State University School of Medicine, Center for Molecular Medicine and Genetics, Detroit, Michigan, USA (with Robert H. Rownd, founder and director of CMMG 1988-96)
2018-2023 Board of Directors, Biomed Industries, Inc, San Jose, California, USA
2018- present, Consultant, Senior Research Fellow, NeuroActiva, Inc, San Jose, California, USA
Past research on cell and developmental biology, molecular biology of extracellular matrix (ECM) proteins, matrix metalloproteinase (MMP) enzymes, gene cloning and transcriptional regulation of gene expression. Major research support provided by the National Institutes of Health (NIH) for 18 years, $4,5 million
Current research interests include drug discovery and clinical development for the treatment and prevention of Alzheimer’s disease and other cognitive, neurologic and psychiatric brain disorders
Published research in 105 papers, reviews and book chapters. 7768 citations. Top 10 papers cited by 3462 (Google Scholar)
Invited speaker at international conferences. Most recently at Vascular Dementia, January 2019, Stockport, UK, ASIC2019, February 2019, San Francisco, USA, WCAP (World Congress of Asian Psychiatry), February 2019, Sydney, Australia, and Psychogeriatric Congress, November 2019, Wroclaw, Poland.
Together with Lloyd Tran organized the first Alzheimer Society International Congress (ASIC2019), a 4-day meeting at Crowne Plaza San Francisco Airport, February 18-21, 2019. Helped arrange and invite speakers for a 90-min webinar on Lecanemab in Alzheimer’s disease, sponsored by Alzheimer International Society, June 22, 2023.
Kurkinen M, Daly T (2024) Survival time in Alzheimer’s disease: an overlooked measure of disease modification. Adv Clin Exp Med, submitted
Daly T, Kurkinen M (2024) Measuring our language about anti-amyloid antibodies in Alzheimer’s disease: technical, theoretical, and lay language considerations. Clin Neurol Neurosurg 241:108314
Kurkinen M (2024) Anti-amyloid therapies do not slow Alzheimer’s disease progression. Dementia
Neuropsychol 17:e20230099
Kurkinen M (2023) Donanemab: Not two without a third. Add Clin Exp Med 32: 1085–1087
Kurkinen M (2023) Lecanemab (Leqembi) is not the right drug for patients with Alzheimer’s disease. Adv Clin Exp Med 32: 943–947
Kurkinen M, Fułek M, Fułek K, Beszłej JA, Kurpas D, Leszek J (2023) The amyloid cascade hypothesis in Alzheimer’s disease: Should we change our thinking? Biomolecules 13: 453
Kurkinen M (2022) Astrocyte glutamate transporter EAAT2 in Alzheimer dementia. Glutamate and Neuropsychiatric Disorders: Current and Emerging Treatments (Zoran Pavlovic, Ed.) Springer Nature, Berlin, Germany, pp. 229–260
Kurkinen M, Tran L (2021) Aduhelm: The best hope for Alzheimer’s patients or the worst decision the FDA ever made? J Alzheimers Dis 84: 969-971
Kurkinen M (2021) Alzheimer’s trials: A cul-de-sac with no end in sight. Adv Clin Exp Med 30: 653-654
Kurkinen M (2018) Alzheimer’s dementia drug discovery: targeting astrocyte glutamate uptake. Conn’s Handbook of Models for Human Aging, 2nd Ed (Ronald Conn and Jeffrey Ram, Eds.) Elsevier, pp. 587-591
Kurkinen M (2017) The amyloid hypothesis is too good to be true. Alzheimers Dement Cogn Neurol 1, 1- 9
© 6/12/2024 Markku Kurkinen
Glutamate, an essential amino acid, is neurotoxic. In synaptic glutamate signaling, too much glutamate leads to loss of synapses and, in the end, death of neurons. Synaptic glutamate signaling is regulated by glutamate transporter EAAT2, which represents 1% of brain protein expressed on astrocytes that cover synapses. As soon as the glutamate signaling starts, it is stopped in one millisecond by EAAT2, which binds and transports glutamate from the synapses into astrocytes. Alzheimer patients’ brains have less EAAT2. In experimental Alzheimer mouse models, decreasing EAAT2 expression enhances disease progression, and increasing EAAT2 expression slows disease progression. These observations indicate EAAT2 as novel target in the discovery and clinical development of drugs to treat and prevent AD.
We have described a simple assay to find drugs that activate EAAT2 and increase glutamate uptake. In the assay, drugs are screened on EAAT2 reconstituted in liposomes and glutamate uptake is measured by red light emission. The assay, in a high-throughput screening (HTS) format, enables the analysis of millions of drugs, chemical compounds and natural products in a short period of time.
In the next step, EAAT2 activating drugs are screened against NCX (sodium calcium exchange) protein reconstituted in liposomes to eliminate drugs that affect NCX activity, and thereby causing adverse events due to heart involvement. Next, the drugs passing this test are screened for crossing the blood brain barrier in a cell culture model that correlates with brain entrance of drugs. Finally, the drugs are tested in an astrocyte-neuron culture to find the drugs that activate EAAT2, increase glutamate uptake and protect neurons against glutamate induced neurotoxicity.
(c) Markku Kurkinen 7/17/2024
1. Korpinen EL, Kurkinen M, Nummi M, Enari TM (1974) Studies on Stachybotrus alternans. III. Chromatographic separation and tissue culture toxicity tests of Stachybotrus toxins. Acts Path Microbiol Scand B 82, 7-11
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2. Korpinen EL, Kurkinen M (1977) Tissue culture techniques in mycotoxin studies. Zeszyty problemowe nauk rolnicyzh 1977, z. 189. Second IUPAC international Meeting on Mycotoxin, 23-25 July, 1974, Pulway, Poland, pp 291-293
3. Kurkinen M, Vaheri A (1977) Fibronectin matrix: antibody-induced reorganization in human fibroblast cultures. Cell Biol Internat Reports 1, 469-475
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4. Vaheri A. Mosher DF, Wartiovaara J, Keski-Oja J, Kurkinen M, Stenman S (1977) Interactions of fibronectin, a cell-type specific surface-associated glycoprotein. Cell Interactions in Differentiation (M. Karkinen-Jääskeläinen, L. Saxen and L. Weiss, Eds.), Academic Press, New York, pp 311-323
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5. Kurkinen M, Wartiovaara J, Vaheri A (1978) Cytochalasin B releases a major surface-associated glycoprotein, fibronectin, from cultured fibroblasts. Exp Cell Res 111, 127-137
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6. Vaher A, Mosher DF, Saksela O, Keski-Oja J, Kurkinen M (1978) Effects of thrombin, pother proteases and malignant transformation on the major cell surface-associated glycoprotein, fibronectin. Proc 11th FEBS Meeting, Copenhagen, 1977 (P. Schambye, Ed.), vol. 47. Pergamon Press, Oxford, pp 137-145
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7. Vaheri A, Kurkinen M, Lehto VP, Linder E, Timpl R (1978) Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: Fibronectin and procollagen. Proc Natl Acad Sci USA 75, 4944-4948
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8. Kurkinen M, Saraste J (1978) Täytyykö geenimanipulaatiotutkimus kieltää? (Should research on gene manipulation be banned?, in Finnish) Tiede ja Edistys 1, 71-74. Published also in Helsingin Lääkärilehti 6, 30-34
9. Keski-Oja J, Kurkinen M, Saksela O, Vaheri A (1978) Fibronektiini, sidekudoksen ja plasman glykoproteiini (Fibronectin, a glycoprotein of connective tissue and plasma, in Finnish). Duodecim 94, 304-312
10. Vaheri A, Alitalo, K, Hedman K, Keski-Aja J, Kurkinen M, Wartiovaara J (1978) Fibronectin and the pericellular matrix in normal and transformed adherent cells. Ann N.Y. Acad Sci 312, 343-353
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1-10 482
11. Virtanen I, Kurkinen M, Lehto VP (1979) Nucleus-anchoring cytoskeleton on chicken red blood cells. Cell Biol Internat Reports 3, 157-162
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12. Hedman K, Kurkinen M, Alitalo K, Vaheri A, Johansson S, Höök M (1979) Isolation of the pericellular matrix of human fibroblast cultures. J Cell Biol 81, 83-91
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13. Kurkinen M, Alitalo K, Vaheri A, Stenman S, Saxen L (1979) Fibronectin in the development of embryonic chick eye. Devel Biol 69, 589-600
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14. Kurkinen M, Alitalo K (1979) Fibronectin and procollagen produced by a clonal line of Schwann cells. FEBS Lett 102, 64-68
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15. Kurkinen M (1979) Pericellular Fibronectin. PhD thesis, University of Helsinki, Finland
16. Krieg T, Timpl R, Alitalo K, Kurkinen M, Vaheri A (1979) Type III procollagen is the major collagenous component produced by a continuous rhabdomyosarcoma cell line. FEBS Lett 104, 405-409
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17. Vaheri A, Alitalo K, Hedman K, Kurkinen M, Saksela O, Vartio T (1979) Fibronectin and its loss in malignant transformation. Colloc. Intern du C.N.R.S. 289, 369-378
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18. Alitalo K, Kurkinen M, Vaheri A, Krieg T, Timpl R (1980) Extracellular matrix components synthesized by human amniotic epithelial cells in culture. Cell 19, 1053-1062
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19. Kurkinen M, Valerie A, Roberts PJ, Stenman S (1980) Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Invest 43, 47-51
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20. Kurkinen M, Alitalo K, Hedman K, Vaheri A (1980) Fibronectin, pro-collagen and the pericellular matrix in normal and transformed fibroblast cultures. Biology of Collagen (A. Viidik, Ed.), Academic Press, New York, p.p. 223-235
11-20 1453
21. Vaheri A, Keski-Oja J, Vartio T, Alitaslo K, Kurkinen M (1980) Structure and functions of fibronectin. Gene Families of Collagen and Other Proteins (J. Rotholz, Ed.),
Elsevier, North-Holland, New York, pp 161-178
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22. Alitalo K, Kurkinen M, Vaheri A, Virtanen I, Rohde H, Timpl R (1980) Basal lamina glycoproteins are produced by neuroblastoma cells. Nature 287, 465-466
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23. Kurkinen M, Vartio T, Vaheri A (1980) Polypeptides of human fibronectin are similar but not identical. Biochem Biophys Acta 624, 490-498
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24. Hogan BLM, Cooper AR, Kurkinen M (1980) Incorporation into Reichert’s membrane of laminin-like extracellular proteins synthesized by parietal endoderm cells of the mouse embryo. Devel Biol 80, 289-300
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25. Kurkinen M (1981) Fidelity of protein synthesis affects the read-through translation of tobacco mosaic virus RNA. FEBS Lett 124, 79-83
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26. Cooper AR, Kurkinen M, Taylor A, Hogan BLM (1981) Studies of the biosynthesis of laminin of murine parietal endoderm cells. Eur J Biochem 119, 189-197
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27. Alitalo K, Kurkinen M, Virtanen I, Melström K, Vaheri A (1982) Deposition of basement membrane proteins in attachment and neurotic formation of cultured murine C-1300 neuroblastoma cells. J Cell Biochem 18, 25-35
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28. Hogan BLM, Taylor A, Kurkinen M, Couchman JR (1982) Synthesis and localization of two sulfated glycoproteins associated with basement membranes and the extracellular matrix. J Cell Biol 95, 197-204
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29. Kurkinen M, Foster L, Barlow DP, Hogan BLM (1982) In vitro synthesis of type IV procollagen. J Biol Chem 257, 15151-15155
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30. Kurkinen M, Barlow DP, Jenkins JR, Hogan BLM (1983) In vitro synthesis of laminin and entactin polypeptides. J Biol Chem 258, 6543-6548
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21-30 893
31. Kurkinen M, Barlow DP, Helfman DM, Williams JG, Hogan BLM (1983) Isolation of cDNA clones for basal lamina components: type IV procollagen. Nucl Acids Res 11, 6199-6209
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32. Schneider C, Kurkinen M, Graeves M (1983) Isolation of cDNA clones for human transferrin receptor. EMBO J 2, 2259-2263.
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33. Lane EB, Hogan BLM, Kurkinen M, Garrels JI (1983) Co-expression of vimentin and cytokeratins in parietal endoderm of the mouse embryo. Nature 303, 701-703
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34. Kurkinen M, Cooper AR, Barlow DP, Jenkins JI, Hogan BLM (1983) Gene expression during parietal endoderm differentiation in mouse embryos and teratocarcinoma cells. Teratocarcinoma Stem Cells (L.M. Silver, G.R. Martin and S. Strickland, Eds.) Cold Spring Harbor Conferences on Cell Proliferation, Vol. 10, Cold Spring Harbor Laboratory, New York, pp 389-401
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35. Kurkinen M, Barlow DP, Hogan BLM (1984) Reichert’s membrane as a model for studying the biosynthesis and assembly of basement membrane components. CIBA Found 108, 60-69
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36. Barlow DP, Green MN, Kurkinen M, Hogan BLM (1984) Sequencing of laminin B chain cDNA reveals C-terminal regions of coiled-coil alpha helix. EMBO J 3, 2355-2362
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37. Kurkinen M, Taylor A, Garrels JI, Hogan BLM (1984) Cell surface-associated proteins which bind native type IV collagen and gelatin. J Biol Chem 259, 5915-5922
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38. Pihlajaniemi T, Tryggvason K, Myers JC, Kurkinen M, Leo R, Cheung MC, Prockop,DJ, Boyd CD (1985) cDNA clones coding for the proα1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain. J Biol Chem 260, 7681-7687
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39. Solomon E, Hiorns LR, Spurr N, Kurkinen M, Barlow DP, Hogan BLM, Dalgleish R (1985) Chromosomal assignments of the genes coding for human types II, III and IV collagen. A dispersed gene family. Proc Natl Acad Sci USA 82, 3330-3334
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40. Kurkinen M, Bernard MP, Barlow DP, Chow LT (1985) Characterization of 64, 123 and 182 base pair exons in the mouse α2(IV) collagen gene. Nature 317, 177-179
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31-40 1385
41. Soininen R, Tikka L, Chow LT, Pihlajaniemi T, Kurkinen M, Precook DJ, Boyd CD, Tryggvason K (1985) Large introns in the 3’-end of the gene for the proα1(IV) chain of human basement membrane collagen. Proc Natl Acad Sci USA 83, 1568-1572
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42. Kurkinen M, Barlow DP, Hogan BLM (1985) Tissue-specific gene expression in mouse F9 embryonal carcinoma cells: Type IV collagen. Ann N.Y. Acad Sci 460, 267-273
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43. Fessler JH, Duncan KG, Blumberg B, Kurkinen M, Sharp J, and Fessler LI (1985) Assembly of the collagen IV scaffold of basement membrane, and tyrosine sulfation of matrix components. Basement Membranes (S. Shibata, Ed.), Elsevier, pp 89-93
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44. Hogan BLM, Barlow DP, Green MN, Elliot RW, McVey J, Patel G, Kurkinen M, Cooper AR (1985) Laminin: towards the structure of the protein and its genes. Basement Membranes (S. Shibata, ed.), Elsevier, North-Holland, pp 147-154
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45. Soininen R, Chow LT, Kurkinen M, Tryggvason K, Prockop DJ (1986) The gene for the α1(IV) chain of human type IV procollagen: The exon structures do not coincide with the two structural subdomains of the globular carboxy-terminus of the protein. EMBO J 5, 2821-2823
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46. Blumberg B, Fessler LI, Kurkinen M, Fessler JH (1986) Biosynthesis and supramolecular assembly of procollagen IV in neonatal lung. J Cell Biol 103, 1711-1719
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47. Pihlajaniemi T, Myllylä R, Seyer J, Kurkinen M, Prockop DJ (1987) Partial characterization of a low molecular weight human collagen that undergoes alternative splicing. Proc Natl Acad Sci USA 84, 940-944
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48. Solomon E, Hall V, Kurkinen M (1987) The human α2(IV) collagen gene, COL4A2, is syntenic with the α1(IV) gene, COL4A1, on chromosome 13. Am J Hum Genet 51, 125-127
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49. Hostikka SL, Kurkinen M, Tryggvason K (1987) Nucleotide sequence coding for the human type IV collagen α2 chain cDNA reveals extensive homology with the NC-1 domain of α1(IV) but not with the collagenous domain or 3’ untranslated region. FEBS Lett 216, 281-286
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50. Kurkinen M, Condon MR, Blumberg B, Barlow DP, Quinones S, Saus J, Pihlajaniemi T (1987) Extensive homology between the carboxyl-terminal peptides of mouse α1(IV) and α2(IV) collagen. J Biol Chem 262, 8496-8499
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41-50 292
51. Blumberg B, Mac Krell AJ, Olson PF, Kurkinen M, Monson JM, Natzle JE, Fessler JH (1987) Basement membrane procollagen IV and its specialized carboxyl domain are conserved in Drosophila, mouse and human. J Biol Chem 262, 5947-5950
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52. Boot-Handford RP, Kurkinen M, Prockop DJ (1987) Steady state levels of mRNAs coding for the type IV collagen and laminin polypeptide chains of basement membranes exhibit marked tissue-specific stoichiometric variations in the rat. J Biol Chem 262, 12475-12478
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53. Kurkinen M (1988) Gene expression in the early mouse embryo and cultured cells. Human Achondroplasia (B. Nicoletti, S.E. Kopits, B. Ascani and V.A. McKusick, Eds.) Plenum Publishing Co, New York, pp 73-80
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54. Boyd CD, Toth-Fejel S, Gadi IK, Litt M, Condon MR, Kolbe M, Hagen IK, Kurkinen M, MacKenzie IW, Magnesia E (1988) The genes coding for human proa1(IV) collagen and proa2(IV) collagen are both located at the end of the long arm of chromosome 13. Am J Hum Genet 42, 309-314
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55. Poulson R, Kurkinen M, Prockop DJ, Boot-Handford RP (1988) Increased steady-state levels of laminin B1 mRNA in kidneys of long-term Streptozotocin-diapetic rats. No effect of an aldose reductase inhibitor. J Biol Chem 263, 6742-6745
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56. Saus J, Quinones S, Otani Y, Nagase H, Harris ED Jr, Kurkinen M (1988) The complete primary structure of human matrix metalloproteinase-3 (MMP-3): Identity with stromelysin. J Biol Chem 263, 6742-6745
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57. Kaytes P, Wood L, Theriault N, Kurkinen M, Vogeli G (1988) Head-to-head arrangement of type IV collagen genes. J Biol Chem 263, 19274-19277
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58. Muthukumaran G, Blumberg G, Kurkinen M (1989) The complete primary structure for the α1-chain of mouse collagen IV. Differential evolution of collagen IV domains. J Biol Chem 264, 6310-6317
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59. Saus J, Quinones S, Mac Krell A, Blumberg B, Muthukumaran G, Pihlajaniemi T, Kurkinen M (1989) The complete primary structure of mouse α2(IV) collagen: Alignment with mouse α1(IV) collagen. J Biol Chem 264, 6318-6324
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60. Quinones S, Saus J, Otani Y, Harris ED Jr, Kurkinen M (1989) Transcriptional regulation of human stromelysin. J Biol Chem 264, 8339-8344
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51-60 974
61. Buttice G, Kaytes P, D’Armiento J, Vogel G, Kurkinen M (1990) Evolution of collagen IV genes from a 54-base pair exon; A role for introns in gene evolution. J Mol Evol 30, 479-488
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62. Blumberg B, Kurkinen M (1990) Structure and evolution of collagen IV genes. Extracellular Matrix Genes (L. Sandell and C. Boyd, Eds.), Academic Press, New York, pp. 115-135
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63. Fecker L, Ekblom P, Kurkinen M, Ekblom M (1990) A genomic clone encoding a novel proliferation dependent histoneH2A.1 mRNA enriched in the poly(A)+ fraction. Mol Cell Biol 10, 2848-2854
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64. Sawai T, Murakami K, Otani Y, Kurkinen M, Kyogoku M, Hayashi M (1990) Stromelysin synthesizing cells in the synovial tissue of rheumatoid arthritis demonstrated by in situ hybridization and immunohistochemical methods. Tohoku J Exp Med 160, 285-286
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65. Otani Y, Quinones S, Saus J, Kurkinen M, Harris ED Jr (1990) Cycloheximide induces stromelysin mRNA in cultured human fibroblasts. Eur J Biochem 192, 75-79
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66. Buttice G, Kurkinen M (1990) Mini-transfections on 96-well microtiter plates. Nucl Acids Res 18, 3079
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67. Buttice G, Quinones S, Kurkinen M (1991) The AP-1 site is required for basal expression but is not necessary for TPA-response of the human stromelysin gene. Nucl Acids Res 19, 3723-3731
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68. Mauviel A, Kähäri VM, Kurkinen M, Evans CH, Uitto J (1992) Leukoregulin, a T-cell derived cytokine, upregulates stromelysin-1 gene expression in human dermal fibroblasts. Evidence for the role of an AP-site in transcriptional activation. J Cell Biochem 50, 53-61
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69. Mauviel A, Kähäri VM, Chen YQ, Kurkinen M, Evans CH, Uitto J (1992) Transcriptional activation of fibroblast stromelysin-1 and collagenase gene expression by a novel lymphokine, leukoregulin. Trans Assoc Am Phys 105, 100-109
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70. Buttice G. Kurkinen M (1993) A polyomavirus enhancer A-binding protein-3 site and Ets-2 protein have a major role in the 12-O-tetradecanoylphorbol-13-acetate response of the human stromelysin gene. J Biol Chem 268, 7186-7204
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61-70 420
71. Tanaka S, Kaytes P, Kurkinen M (1993) An enhancer for transcription of collagen IV genes is activated by F9 cell differentiation. J Biol Chem 268, 8862-8870
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72. Quintavalla JC, Berg RA, Beavis AJ, Piccoli SP, Rediske JJ, Kurkinen M, Patrick RA, Roberts FM (1993) Differential induction of stromelysin mRNA by bovine articular chondrocytes treated with interferon-gamma and interleukin-1β. J Cell Physiol 154, 113-121
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73. Patel MN, Kurkinen M (1993) Double-reporter vectors for studying bidirectional gene transcription. Biotechniques 15, 615-620
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74. Mauviel A, Halcin C, Vasiloudes P, Parks WC, Kurkinen M, Uitto J (1994) Uncoordinated regulation of collagenase, stromelysin and tissue inhibitor of metalloproteinase genes by prostaglandin E2. Selective enhancement of collagenase gene expression in human dermal fibroblasts in culture. J Cell. Biochem 54, 465-472
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75. Buttice G, Kurkinen M (1994) Oncogenes control collagenase and stromelysin gene expression. Extracellular Matrix in the Kidney. Contrib Nephrol, Vol. 197 (H. Koide and T. Hayashi, Eds.), Karger, pp 101-107
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76. Yang M, Kurkinen M (1994) Different mechanisms of regulation of the human stromelysin and collagenase genes. Analysis by reverse-transcription-coupled-PCR assay. Eur J Biochem 222, 651-658
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77. Quinones S, Buttice G, Kurkinen M (1994) Promoter elements in the transcriptional activation of the human stromelysin gene by the inflammatory cytokine, Interleukin-1. Biochem J 302, 471-477
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78. Sawai T, Uzuki M, Harris ED Jr, Kurkinen M, Trelstad RI, Hayashi M (1996) In situ hybridization of stromelysin mRNA in the synovial biopsies from rheumatoid arthritis. Tohoku J Exp Med 178, 315-330
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79. Benbow U, Buttice G, Nagase H, Kurkinen M (1996) Characterization of the 46-kDa intermediates of matrix metalloproteinase-3 (stromelysin-1) obtained by site-directed mutation of phenylalanine-83. J Biol Chem 271, 10715-10722
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80. Ye S, Eriksson P, Hamsten A, Kurkinen M, Humpries SE, Henry AM (1996) Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem 271, 13055-13061
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71-80 940
81. Yang M, Hayashi K, Hayashi M, Fuji JT, Kurkinen M (1996) Cloning and developmental expression of a membrane type-matrix metalloproteinase from chicken. J Bio Chem 271, 25548-25554
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82. Buttice G, Duterque-Coquillaud M, Basuyaux JP, Carrere S, Kurkinen M, Stehelin D (1996) Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/jun complex. Oncogene 13,, 2297- 2306
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83. Gervasi DC, Raz A, Dehem M, Yang M, Kurkinen M, Fridman R (1996) Carbohydrate-mediated regulation of matrix metalloproteinase-2 activation in normal human fibroblasts and fibrosarcoma cells. Biochem Biophys Res Commun 228, 530-538
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84. Yang M, Murray MT, Kurkinen M (1997) A novel matrix metalloproteinase gene (XMMP) encoding vitronectin-like motifs is transiently expressed in Xenopus laevis early embryo development. J Biol Chem 272, 13527-13533
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85. Yang M, Kurkinen M (1998) Cloning and developmental regulation of tissue inhibitor of metalloproteinase-3 (TIMP3) in Xenopus laevis early embryos. Gene 211, 95-100
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86. Yang M, Kurkinen M (1998) Cloning and characterization of a novel matrix metalloproteinase (MMP), CMMP, from chicken embryo fibroblasts. CMMP, Xenopus XMMP and human MMP19 have a conserved unique cysteine in the catalytic domain. J Biol Chem 273, 17893-17900
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87. Jayaraman G, Srinivas R, Duggan C, Ferreira E, Swaminathan S, Somasundaram K, Williams J, Hauser C, Kurkinen M, Dhar R, Wetzman S, Buttice G, Thimmapaya B (1999) p300/CBP interactions with Ets-1 and Ets-2 in the transcriptional activation of the human stromelysin promoter. J Bio Chem 274, 17342-17352
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88. Olson M, Emblem M, Fecker L, Kurkinen M, Ekblom P (1999) cDNA cloning and embryonic expression of mouse nuclear pore membrane glycoprotein 210 mRNA. Kidney Int 56, 827-838
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of note, our paper made the cover as the featured article in Kidney International February 1999 issue
89. Yang M, Kurkinen M (2002) Xenopus XMMP, matrix metalloproteinase-21. Handbook of Proteolytic Enzymes, 2nd Edition (A. Barrett, N. Rawlings and F. Woessner, Eds.) Academic Press, p.132
Book cited by 40. 3rd Edition, 2013 (N. Rawlings and G. Salvesen, Eds,) cited by 348.
90. Yang M, Kurkinen M (2002) Chicken CMMP, matrix metalloproteinase-22. Handbook of Proteolytic Enzymes, 2nd Edition (A. Barrett, N. Rawlings and F. Woessner, Eds.) Academic Press, p.133
Book cited by 40. 3rd Edition, 2013 (N. Rawlings and G. Salvesen, Eds,) cited by 348.
91. Ye CJ, Stevens JB, Liu G, Bremer SW, Jaiswal AS, Ye KJ, Lin MF, Lawrenson L, Lancaster WD, Kurkinen M, Liao JD, Gairola CG, Shekhar MPV, Narayan S, Miller FR, Heng HHQ (2009) Genome based cell population heterogeneity promotes tumorigenicity: The evolutionary mechanism of cancer. J Cell Physiol 219, 288-300
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92. Stevens JB, Abdullah BY, Liu G, Horne SD, Bremer SW, Ye KJ, Huang JY, Kurkinen M, Ye CJ, Hong HHQ (2013) Heterogeneity of cell death. Cytogenet Genome Res 139, 164–173
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93. Abdullah BY, Horne SD, Kurkinen M, Stevens JB, Liu G, Ye CJ, Justin Barbat J, Bremer SW, Heng HHQ (2014) Ovarian cancer evolution through stochastic genome alterations: defining the genomic role in ovarian cancer. Syst Biol Reprod Med 60, 2-13
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94. Kurkinen M (2015) Kuka Lypsää Lehmät? Fram, Finland. A collection of 47 autobiographical sketches, in Finnish. Original title Who’s Gonna Milk the Cows?
95. Kurkinen M (2017) The amyloid hypothesis is too good to be true. Alzheimers Dement Cogn Neurol 1, 1- 9
14
96. Kurkinen M (2018) Alzheimer’s dementia drug discovery: targeting astrocyte glutamate uptake. Conn’s Handbook of Models for Human Aging, 2nd Ed (Ronald Conn and Jeffrey Ram, Eds.) Elsevier, pp. 587-591
1 (book cited by 16)
97. Kurkinen M (2021) Alzheimer’s trials: A cul-de-sac with no end in sight. Adv Clin Exp Med 30, 653-654
10
98. Kurkinen M, Tran L (2021) Aduhelm: The best hope for Alzheimer’s patients or the worst decision the FDA ever made? J Alzheimers Dis 84, 969-971
7
99. Kurkinen M (2022) Astrocyte glutamate transporter EAAT2 in Alzheimer dementia. Glutamate and Neuropsychiatric Disorders: Current and Emerging Treatments (Zoran Pavlovic, Ed.) Springer Nature, Berlin, Germany, pp. 229–260
3 (book cited by 3)
100. Kurkinen M, Fułek M, Fu łek K, Beszłej JA, Kurpas D, Leszek J (2023) The amyloid cascade hypothesis in Alzheimer’s disease: should we change our thinking? Biomolecules 13, 453
23
101. Kurkinen M (2023) Lecanemab (Leqembi) is not the right drug for patients with Alzheimer’s disease. Adv Clin Exp Med 32, 943–947
102. Kurkinen M (2023) Donanemab: Not two without a third. Adv Clin Exp Med 32, 1085–1087
103. Kurkinen M (2024) Anti-amyloid therapies do not slow Alzheimer’s disease progression. Dementia Neuropsychol17:e20230099.
104. Daly T, Kurkinen M ,(2024) Measuring our language about
amyloid antibodies in Alzheimer’s disease: technical, theoretical, and lay language considerations. Clin Neurol Neurosurg, in press
MARKKU KURKINEN, PhD
Born: October 8, 1949, Mikkeli, Finland
Citizenship: Finland. Permanent resident of USA
1975 MS Department of Biochemistry, University of Helsinki, Finland
1979 PhD Department of Virology, University of Helsinki, Finland
TRAINING AND VISITING SCIENTIST
1979 Visiting scientist (3 months)
c/o Brigid Hogan
Imperial Cancer Research Fund (ICRF), Mill Hill, London, UK
1982 Visiting scientist (5 weeks)
c/o David Helfman
Cold Spring Harbor Laboratory, New York, USA
ICRF Fellow
c/o Brigid Hogan
Imperial Cancer Research Fund, Mill Hill, London, UK
1983-84 EMBO Fellow (9 months)
c/o Sid Strickland
State University of New York, Stony Brook, New York, USA
and
c/o Darwin J. Prockop
University of Medicine and Dentistry New Jersey (UMDNJ)
Rutgers Medical School, Piscataway, New Jersey, USA
1984 Visiting scientist (5 weeks)
c/o Peter Ekblom
Max Planck Institute for Developmental Biology, Tubingen, Germany
1985 Visiting scientist (1 week)
c/o John Fessler
UCLA, Molecular Biology Institute, Los Angeles, California, USA
1985 Visiting scientist (3 weeks)
c/o Claudio Schneider
EMBL, Heidelberg, Germany
2000 Visiting scientist (3 days)
c/o Sergei Sokol
Harvard University, Boston, Massachusetts, USA
1984-85 Assistant Professor (adjunct)
Department of Biochemistry
UMDNJ-Rutgers Medical School
Piscataway, New Jersey, USA
1985-86 Associate Professor (adjunct)
Departments of Biochemistry and Medicine
UMDNJ-Rutgers Medical School
Piscataway, New Jersey, USA
1986-92 Associate Professor (tenure)
Department of Medicine
UMDNJ-Robert Wood Johnson Medical School
(formerly Rutgers Medical School)
Piscataway, New Jersey, USA
Chief, Division of Connective Tissue Research
Department of Medicine
UMDNJ-Robert Wood Johnson Medical School
Piscataway, New Jersey, USA
1992-2019 Professor (tenure)
Wayne State University School of Medicine
Center for Molecular Medicine and Genetics
Detroit, Michigan, USA
2020- Research Fellow
NeuroActiva, Inc.
San Jose, California, USA
2002 Nagoya University, Japan
c/o Kazuhito Takeshima
4.5 months (canceled)
2002 UCLA, Los Angeles, California, USA
c/o Eddy de Robertis
4.5 months (canceled)
2010 University of Manchester, Manchester, UK
c/o Alexej Verkhratsky
4.5 months (canceled)
2010 Medical College of Georgia, Augusta, USA
c/o Joe Tzien
4.5 months
2014 University of Manchester, Manchester, UK
c/o Alexej Verkhratsky
4.5 months
AAAS American Association for the Advancement of Science
ASMB American Society for Matrix Biology
ISMB International Society for Matrix Biology
ISTAART international Society to Advance Alzheimer’s Research and Treatment
Research Assistant of the Academy of Finland
1976 Finnish Cultural Foundation
1977 Finnish Cancer Society
1978 Finnish Cancer Society
1982 EMBO Short Term Fellowship
1982 Royal Society Fellowship
EMBO Long Term Fellowship
Center for Molecular Medicine and Genetics (CMMG)
1993-95 Chair, Faculty Recruitment, Joint & Adjunct Appointments,
Graduate and Medical Training/Curriculum, Graduate Student recruitment,
Graduate Program in Cancer Biology, Seminar Series
1995-96 Co-chair, Graduate Student recruitment, Graduate Program in Cancer
Biology, Promotion & Tenure & Salary Committee
1996-97 Faculty Recruitment on Human Genetics and Gene Therapy
Graduate Student Recruitment, Graduate Program in Cancer Biology
Kitchen Cabinet, Promotion & Tenure & Salary Committee
1997-98 Graduate Student Recruitment, Seminar Series
Graduate Program in Cancer Biology
Research Support, Promotion & Tenure & Salary Committee
1998-99 Graduate Student Recruitment
Seminar Series
Graduate Program in Cancer Biology
Research Support
1999-01 Graduate Student Recruitment
Graduate Program in Cancer Biology
Promotion & Tenure & Salary
2007-10 Education/Outreach Committee
2015-19 Graduate Students Research Day
Member, Judges Committee
see Appendix 1. Research Activity for more details
1997 Member of Organizing Committee: Frontiers in Molecular Medicine
October 3-4, 1997, Detroit USA, A Memorial Symposium dedicated to Robert
H. Rownd, the founder of CMMG
1998 Designed and helped develop the logo, font and color of CMMG
2014-16 Alzheimer’s Advocacy, UsAgainstAzheimer’s, Alzheimer’s Association
Including 2 visits a year to Washington DC and Capitol Hill to meet
Representatives and Senators
2018- Editorial Board of Advances in Geriatric Medicine and Research (AGMR)
2019 Co-Chair, Organizing Committee, Alzheimer Society International Congress
(ASIC2019), February 18-21, 2019, San Francisco, California, USA
1998 Proctor & Gamble, Cincinnati, Ohio, USA
2018- Scientific Advisory Board, NeuroActiva, Inc. San Jose, California, USA
1989 NIH Ad hoc, Pathobiochemistry
1995 NIH Ad hoc, New Horizons in Osteoarthritis Research (RFA)
1997 AHA Ad hoc, Michigan Chapter
see Appendix 1. Research Activity for details
Advances in Geriatric Medicine and Research, Biotechniques, Differentiation, Development, Gene, Journal of Alzheimer’s Disease, Journal of Biological Chemistry, Journal of Clinical Investigation, Journal of Histochemistry and Cytochemistry, Matrix Biology
1983 State University of New York, Stony Brook, New York, USA
1984-92 University of Medicine and Dentistry of New Jersey, Piscataway, New
Jersey, USA
1992 – Wayne State University School of Medicine, Detroit, Michigan, USA
Of note, by nature this a narrative of history of the technicians, graduate students and post-doctoral fellows, who worked with me in the lab in 1984-92, then at UMDNJ, many of whom became independent scientists (with research funding from NIH).
Elizabeth Lesko (originally from Budapest, Hungary) came to the lab to wash the dishes and all them sequencing plates we used day in-and-out to determine the DNA sequence of type IV collagen proteins and genes, as well as matrix metalloproteinase enzymes. Very soon she was running our lab 1984-92. Every year, UMDNJ asked to nominate somebody for “Best in the Lab”, so always voted for Liz, and she got the $1,000 prize every year.
Michael Condon, PhD, went the Memorial Sloan Kettering Institute, New York, USA. Bruce Blumberg, PhD, is at UCLA, Los Angeles, USA. Esa Kuismanen, PhD, is now Professor at the University of Helsinki, Finland. Juan Saus, MD, PhD, is Professor at the University of Valencia, Spain. Randall Stevens, MD, is at the CIBA-CEIGY Pharmaceutical Company, New Jersey,USA. Susan Quinones, PhD (NIH R29 1989-94) is an Assistant Professor at the Environmental and Occupational Health Institute, Piscataway, New Jersey, USA. Mukul Patel, PhD, is at UMDNJ-Robert Wood Johnson University Hospital, Newark, New Jersey, USA. Shizuko Tanaka (1951-2007), PhD (NIH R29 1994-99) was a Research Assistant Professor at Mount Sinai Medical School, New York, USA. Giovanna Buttice, PhD, a Staff Member 1994-2004 at the Pasteur Institute, Lille, France. Geetha Muthukumaran completed her PhD work in 1988. Geetha is now at UMDNJ-Robert Wood Johnson Medical School, Department of Microbiology and genetics, Piscataway, New Jersey, USA. Huiming Nie completed his MS work in 1992. Huiming is now at Bristol-Myers-Squibb Pharmaceutical Research Institute, Princeton, New Jersey. Maozhou Yang completed his PhD work in 1993. Mao is now at Henry Ford Hospital, Detroit, Michigan, USA.
1984-88 Geetha Muthukumaran, PhD
1987-93 Maozhou Yang, PhD
1993-95 Huiming Nie, MS
“Developmental Control of Type IV Collagen Synthesis”
National Institutes of Health GM 34090
7/1/84 – 5/30/93
Principal Investigator: Markku Kurkinen
50% Effort
“Control of Collagen Destruction in Arthritis”
National Institutes of Health HAR33714
9/1/80 – 8/31/90
Principal Investigator: Edward D. Harris Jr. 9/1/80 – 11/22/87
Principal Investigator: Markku Kurkinen 11/23/87 – 8/31/90
10% Effort
“Matrix Degrading Proteinases in Human Skin Disorders”
National Institutes of Health HD 24442
8/1/88 – 11/30/93
Principal Investigator: Markku Kurkinen
40% Effort
“Matrix Proteinases in Connective Tissue Diseases”
National Institutes of Health HD24442
12/1/93 – 11/30/97
Principal Investigator: Markku Kurkinen
30% Effort
“Role of Proteases in Breast Cancer Progression”
U.S. Army Medical Research Acquisition AIBS1207
7/1/94 – 6/30/98
Principal Investigator: Rafael Fridman
Co-Principal Investigator: Markku Kurkinen
10% Effort
“Role of TIMPs in P. aeruginosa Corneal Infections”
National Institutes of Health EY11757
7/1/98 – 6/30/01
Principal Investigator: Richard S. Berk
Co-Principal Investigator: Markku Kurkinen
10% Effort
97 papers, reviews and book chapters on biochemistry, cell biology, matrix biology, molecular cloning, gene regulation, Alzheimer dementia. Research interests: Alzheimer dementia, astrocyte glutamate transporter EAAT2, drug discovery, synaptic glutamate signaling in cognitive and psychiatric disorders.
Most recent papers (reviews)
Kurkinen M (2017) The amyloid hypothesis is too good to be true. Alzheimers Dement Cogn Neurol 1 DOI:10.15761/ADCN.1000106
Kurkinen M (2018) Alzheimer’s dementia drug discovery: targeting astrocyte glutamate uptake. Conn’s Handbook of Models for Human Aging, 2nd Ed (Ronald Conn and Jeffrey Ram, Eds.) Elsevier
Kurkinen M (2020) Astrocyte glutamate transporter EAAT2 in Alzheimer dementia. Glutamate and Neuropsychiatric Disorders: Current and Emerging Treatments (Zoran Pavlovic, Ed.) Springer Nature
See Appendix 2. Letter of Intent (LOI) for a research proposal
Alzheimer’s drug discovery: targeting astrocyte glutamate transporter EAAT2 in synaptic glutamate signaling
see Appendix 1. Research Activity for more details
1982-88 several lectures at Gordon Research Conferences, New Hampshire, USA
NIH, Bethesda, Maryland, USA
University of Texas at Tyler, Tyler, Texas, USA
University of Kansas, Kansas City, Kansas, USA
1986 New York Academy of Sciences, New York, USA
Shriner’s Hospital for Sick Children, Portland, Oregon, USA
University of Wisconsin, Madison, Wisconsin, USA
University of Umeo, Sweden
University of Oulu, Finland
2017 13th World Federation of Societies of Biological Psychiatry, Copenhagen,
Denmark
2017 Congress on Invertebrate Models of Human Aging, Naples-Florence, Italy
2018 Vascular Dementia, Paris, France
2018 The Meadows Hospital, Stockport, UK
2018 Dementia and Dementia Care, London, UK
2019 Vascular Dementia Conference, Stockport, UK
2019 Alzheimer Society International Congress, San Francisco, California,
USA
2019 7th World Congress of Asian Psychiatry (WCAP), Sydney, Australia
2019 13th International Conference of Psychogeriatry, Wroclaw, Poland
Top ten papers together cited 2665 times
1. Korpinen EL, Kurkinen M, Nummi M, Enari TM (1974) Studies on Stachybotrus alternans. III. Chromatographic separation and tissue culture toxicity tests of Stachybotrus toxins. Acts Path Microbiol Scand B 82, 7-11
2. Korpinen EL, Kurkinen M (1977) Tissue culture techniques in mycotoxin studies. Zeszyty problemowe nauk rolnicyzh 1977, z. 189. Second IUPAC international Meeting on Mycotoxin, 23-25 July, 1974, Pulway, Poland, pp 291-293
3. Kurkinen M, Vaheri A (1977) Fibronectin matrix: antibody-induced reorganization in human fibroblast cultures. Cell Biol Internat Reports 1, 469-475
4. Vaheri A. Mosher DF, Wartiovaara J, Keski-Oja J, Kurkinen M, Stenman S (1977) Interactions of fibronectin, a cell-type specific surface-associated glycoprotein. Cell Interactions in Differentiation (M. Karkinen-Jääskeläinen, L. Saxon and L. Weiss, Eds.), Academic Press, New York, pp 311-323
5. Kurkinen M, Wartiovaara J, Vaheri A (1978) Cytochalasin B releases a major surface-associated glycoprotein, fibronectin, from cultured fibroblasts. Exp Cell Res 111, 127-137
6. Vaher A, Mosher DF, Saksela O, Keski-Oja J, Kurkinen M (1978) Effects of thrombin, other proteases and malignant transformation on the major cell surface-associated glycoprotein, fibronectin. Proc 11th FEBS Meeting, Copenhagen, 1977 (P. Schambye, Ed.), vol. 47. Pergamon Press, Oxford, pp 137-145
7. Vaheri A, Kurkinen M, Lehto VP, Linder E, Timpl R (1978) Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: Fibronectin and procollagen. Proc Natl Acad Sci USA 75, 4944-4948
(cited 268 times)
8. Kurkinen M, Saraste J (1978) Täytyykö geenimanipulaatiotutkimus kieltää? (a review of recombinant DNA, in Finnish) Tiede ja Edistys 1, 71-74. Published also in Helsingin Lääkärilehti 6, 30-34
9. Keski-Oja J, Kurkinen M, Saksela O, Vaheri A (1978) Fibronektiini, sidekudoksen ja plasman glykoproteiini (Fibronectin, a glycoprotein of connective tissue and plasma, in Finnish). Duodecim 94, 304-312
10. Vaheri A, Alitalo, K, Hedman K, Keski-Aja J, Kurkinen M, Wartiovaara J (1978) Fibronectin and the pericellular matrix in normal and transformed adherent cells. Ann N.Y. Acad Sci 312, 343-353
11. Virtanen I, Kurkinen M, Lehto VP (1979) Nucleus-anchoring cytoskeleton on chicken red blood cells. Cell Biol Internat Reports 3, 157-162
12. Hedman K, Kurkinen M, Alitalo K, Vaheri A, Johansson S, Höök M (1979) Isolation of the pericellular matrix of human fibroblast cultures. J Cell Biol 81, 83-91
(cited 294 times)
13. Kurkinen M, Alitalo K, Vaheri A, Stenman S, Sazen L (1979) Fibronectin in the development of embryonic chick eye. Devel Biol 69, 589-600
14. Kurkinen M, Alitalo K (1979) Fibronectin and procollagen produced by a clonal line of Schwann cells. FEBS Lett 102, 64-68
15. Kurkinen M (1979) Pericellular Fibronectin. PhD thesis, University of Helsinki, Finland
16. Krieg T, Timpl R, Alitalo K, Kurkinen M, Vaheri A (1979) Type III procollagen is the major collagenous component produced by a continuous rhabdomyosarcoma cell line. FEBS Lett 104, 405-409
17. Vaheri A, Alitalo K, Hedman K, Kurkinen M, Saksela O, Vartio T (1979) Fibronectin and its loss in malignant transformation. Colloc. Intern du C.N.R.S. 289, 369-378
18. Alitaolo K, Kurkinen M, Vaheri A, Krieg T, Timpl R (1980) Extracellular matrix components synthesized by human amniotic epithelial cells in culture. Cell 19, 1053-1062
19. Kurkinen M, Vaheri A, Roberts PJ, Stenman S (1980) Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Invest 43, 47-51
(cited 405 times)
20. Kurkinen M, Alitalo K, Hedman K, Vaheri A (1980) Fibronectin, procollagen and the pericellular matrix in normal and transformed fibroblast cultures. Biology of Collagen (A. Viidik, Ed.), Academic Press, New York, pp 223-235
21. Vaheri A, Keski-Oja J, Vartio T, Alitaslo K, Kurkinen M (1980) Structure and functions of fibronectin. Gene Families of Collagen and Other Proteins (J. Rotholz, Ed.), Elsevier, North-Holland, New York, pp 161-178
22. Alitalo K, Kurkinen M, Vaheri A, Virtanen I, Rohde H, Timpl R (1980) Basal lamina glycoproteins are produced by neuroblastoma cells. Nature 287, 465-466
23. Kurkinen M, Vartio T, Vaheri A (1980) Polypeptides of human fibronectin are similar but not identical. Biochem Biophys Acta 624, 490-498
24. Hogan BLM, Cooper AR, Kurkinen M (1980) Incorporation into Reichert’s membrane of laminin-like extracellular proteins synthesized by parietal endoderm cells of the mouse embryo. Devel Biol 80, 289-300
25. Kurkinen M (1981) Fidelity of protein synthesis affects the read-through translation of tobacco mosaic virus RNA. FEBS Lett 124, 79-83
26. Cooper AR, Kurkinen M, Taylor A, Hogan BLM (1981) Studies of the biosynthesis of laminin of murine parietal endoderm cells. Eur J Biochem 119, 189-197
(cited 205 times)
27. Alitalo K, Kurkinen M, Virtanen I, Melström K, Vaheri A (1982) Deposition of basement membrane proteins in attachment and neurotic formation of cultured murine C-1300 neuroblastoma cells. J Cell Biochem 18, 25-35
28. Hogan BLM, Taylor A, Kurkinen M, Couchman JR (1982) Synthesis and localization of two sulfated glycoproteins associated with basement membranes and the extracellular matrix. J Cell Biol 95, 197-204
29. Kurkinen M, Foster L, Barlow DP, Hogan BLM (1982) In vitro synthesis of type IV procollagen. J Biol Chem 257, 15151-15155
30. Kurkinen M, Barlow DP, Jenkins JR, Hogan BLM (1983) In vitro synthesis of laminin and entactin polypeptides. J Biol Chem 258, 6543-6548
31. Kurkinen M, Barlow DP, Helfman DM, Williams JG, Hogan BLM (1983) Isolation of cDNA clones for basal lamina components: type IV procollagen. Nucl Acids Res 11, 6199-6209
32. Schneider C, Kurkinen M, Graeves M (1983) Isolation of cDNA clones for human transferrin receptor. EMBO J 2, 2259-2263.
33. Lane EB, Hogan BLM, Kurkinen M, Garrels JI (1983) Co-expression of vimentin and cytokeratins in parietal endoderm of the mouse embryo. Nature 303, 701-703
(cited 266 times)
34. Kurkinen M, Cooper AR, Barlow DP, Jenkins JI, Hogan BLM (1983) Gene expression during parietal endoderm differentiation in mouse embryos and teratocarcinoma cells. Teratocarcinoma Stem Cells (L.M. Silver, G.R. Martin and S. Strickland, Eds.) Cold Spring Harbor Conferences on Cell Proliferation, Vol. 10, Cold Spring Harbor Laboratory, New York, pp 389-401
35. Kurkinen M, Barlow DP, Hogan BLM (1984) Reichert’s membrane as a model for studying the biosynthesis and assembly of basement membrane components. CIBA Found 108, 60-69
36. Barlow DP, Green MN, Kurkinen M, Hogan BLM (1984) Sequencing of laminin B chain cDNA reveals C-terminal regions of coiled-coil alpha helix. EMBO J 3, 2355-2362
(cited 188 times)
37. Kurkinen M, Taylor A, Garrels JI, Hogan BLM (1984) Cell surface-associated proteins which bind native type IV collagen and gelatin. J Biol Chem 259, 5915-5922
(cited 167 times)
38. Pihlajaniemi T, Tryggvason K, Myers JC, Kurkinen M, Leo R, Cheung MC, Prockop,DJ, Boyd CD (1985) cDNA clones coding for the proα1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain. J Biol Chem 260, 7681-7687
(cited 204 times)
39. Solomon E, Hiorns LR, Spurr N, Kurkinen M, Barlow DP, Hogan BLM, Dalgleish R (1985) Chromosomal assignments of the genes coding for human types II, III and IV collagen. A dispersed gene family. Proc Natl Acad Sci USA 82, 3330-3334
40. Kurkinen M, Bernard MP, Barlow DP, Chow LT (1985) Characterization of 64, 123 and 182 base pair exons in the mouse α2(IV) collagen gene. Nature 317, 177-179
41. Soininen R, Tikka L, Chow LT, Pihlajaniemi T, Kurkinen M, Precook DJ, Boyd CD, Tryggvason K (1985) Large introns in the 3’-end of the gene for the proα1(IV) chain of human basement membrane collagen. Proc Natl Acad Sci USA 83, 1568-1572
42. Kurkinen M, Barlow DP, Hogan BLM (1985) Tissue-specific gene expression in mouse F9 embryonal carcinoma cells: Type IV collagen. Ann N.Y. Acad Sci 460, 267-273
43. Fessler JH, Duncan KG, Blumberg B, Kurkinen M, Sharp J, and Fessler LI (1985) Assembly of the collagen IV scaffold of basement membrane, and tyrosine sulfation of matrix components. Basement Membranes (S. Shibata, Ed.), Elsevier, pp 89-93
44. Hogan BLM, Barlow DP, Green MN, Elliot RW, McVey J, Patel G, Kurkinen M, Cooper AT (1985) Laminin: towards the structure of the protein and its genes. Basement Membranes (S. Shibata, ed.), Elsevier, North-Holland, pp 147-154
45. Soininen R, Chow LT, Kurkinen M, Tryggvason K, Prockop DJ (1986) The gene for the α1(IV) chain of human type IV procollagen: The exon structures do not coincide with the two structural subdomains of the globular carboxy-terminus of the protein. EMBO J 5, 2821-2823
46. Blumberg B, Fessler LI, Kurkinen M, Fessler JH (1986) Biosynthesis and supramolecular assembly of procollagen IV in neonatal lung. J Cell Biol 103, 1711-1719
47. Pihlajaniemi T, Myllylä R, Seyer J, Kurkinen M, Prockop DJ (1987) Partial characterization of a low molecular weight human collagen that undergoes alternative splicing. Proc Natl Acad Sci USA 84, 940-944
48. Solomon E, Hall V, Kurkinen M (1987) The human α2(IV) collagen gene, COL4A2, is sentence with the α1(IV) gene, COL4A1, on chromosome 13. Am J Hum Genet 51, 125-127
49. Hostikka SL, Kurkinen M, Tryggvason K (1987) Nucleotide sequence coding for the human type IV collagen α2 chain cDNA reveals extensive homology with the NC-1 domain of α1(IV) but not with the collagenous domain or 3’ untranslated region. FEBS Lett 216, 281-286
50. Kurkinen M, Condon MR, Blumberg B, Barlow DP, Quinones S, Saus J, Pihlajaniemi T (1987) Extensive homology between the carboxyl-terminal peptides of mouse α1(IV) and α2(IV) collagen. J Biol Chem 262, 8496-8499
51. Blumberg B, Mac Krell AJ, Olson PF, Kurkinen M, Monson JM, Natzle JE, Fessler JH (1987) Basement membrane procollagen IV and its specialized carboxyl domain are conserved in Drosophila, mouse and human. J Biol Chem 262, 5947-5950
52. Boot-Handford RP, Kurkinen M, Prockop DJ (1987) Steady state levels of mRNAs coding for the type IV collagen and laminin polypeptide chains of basement membranes exhibit marked tissue-specific stoichiometric variations in the rat. J Biol Chem 262, 12475-12478
53. Kurkinen M (1988) Gene expression in the early mouse embryo and cultured cells. Human Achondroplasia (B. Nicoletti, S.E. Kopits, B. Ascani and V.A. McKusick, Eds.) Plenum Publishing Co, New York, pp 73-80
54. Boyd CD, Toth-Fejel S, Gadi IK, Litt M, Condon MR, Kolbe M, Hagen IK, Kurkinen M, MacKenzie IW, Magnesia E (1988) The genes coding for human proa1(IV) collagen and proa2(IV) collagen are both located at the end of the long arm of chromosome 13. Am J Hum Genet 42, 309-314
55. Poulson R, Kurkinen M, Prockop DJ, Boot-Handford RP (1988) Increased steady-state levels of laminin B1 mRNA in kidneys of long-term Streptozotocin-diapetic rats. No effect of an aldose reductase inhibitor. J Biol Chem 263, 6742-6745
56. Saus J, Quinones S, Otani Y, Nagase H, Harris ED Jr, Kurkinen M (1988) The complete primary structure of human matrix metalloproteinase-3 (MMP-3): Identity with stromelysin. J Biol Chem 263, 6742-6745
(cited 239 times)
57. Kaytes P, Wood L, Theriault N, Kurkinen M, Vogeli G (1988) Head-to-head arrangement of type IV collagen genes. J Biol Chem 263, 19274-19277
58. Muthukumaran G, Blumberg G, Kurkinen M (1989) The complete primary structure for the α1-chain of mouse collagen IV. Differential evolution of collagen IV domains. J Biol Chem 263, 6310-6317
59. Saus J, Quinones S, Mac Krell A, Blumberg B, Muthukumaran G, Pihlajaniemi T, Kurkinen M (1989) The complete primary structure of mouse α2(IV) collagen: Alignment with mouse α1(IV) collagen. J Biol Chem 264, 6318-6324
60. Quinones S, Saus J, Otani Y, Harris ED Jr, Kurkinen M (1989) Transcriptional regulation of human stromelysin. J Biol Chem 264, 8339-8344
61. Buttice G, Kaytes P, D’Armiento J, Vogeli G, Kurkinen M (1990) Evolution of collagen IV genes from a 54-base pair exon; A role for introns in gene evolution. J Mol Evol 30, 479-488
62. Blumberg B, Kurkinen M (1990) Structure and evolution of collagen IV genes. Extracellular Matrix Genes (L. Sandell and C. Boyd, Eds.), Academic Press, New York, pp. 115-135
63. Fecker L, Ekblom P, Kurkinen M, Ekblom M (1990) A genomic clone encoding a novel proliferation dependent histoneH2A.1 mRNA enriched in the poly(A)+ fraction. Mol Cell Biol 10, 2848-2854.
64. Sawai T, Murakami K, Otani Y, Kurkinen M, Kyogoku M, Hayashi M (1990) Stromelysin synthesizing cells in the synovial tissue of rheumatoid arthritis demonstrated by in situ hybridization and immunohistochemical methods. Tohoku J Exp Med 160, 285-286
65. Otani Y, Quinones S, Saus J, Kurkinen M, Harris ED Jr (1990) Cycloheximide induce stromelysin mRNA in cultured human fibroblasts. Eur J Biochem 192, 75-79
66. Buttice G, Kurkinen M (1990) Mini-transfections on 96-well microtiter plates. Nucl Acids Res 18, 3079
67. Buttice G, Quinones S, Kurkinen M (1991) The AP-1 site is required for basal expression but is not necessary for TPA-response of the human stromelysin gene. Nucl Acids Res 19, 3723-3731
68. Mauviel A, Kähäri VM, Kurkinen M, Evans CH, Uitto J (1992) Leukoregulin, a T-cell derived cytokine, upregulates stromelysin-1 gene expression in human dermal fibroblasts. Evidence for the role of an AP-site in transcriptional activation. J Cell Biochem 50, 53-61
69. Mauviel A, Kähäri VM, Chen YQ, Kurkinen M, Evans CH, Uitto J (1992) Transcriptional activation of fibroblast stromelysin-1 and collagenase gene expression by a novel lymphokine, leukoregulin. Trans Assoc Am Phys 105, 100-109
70. Buttice G. Kurkinen M (1993) A polyomavirus enhancer A-binding protein-3 site and Ets-2 protein have a major role in the 12-O-tetradecanoylphorbol-13-acetate response of the human stromelysin gene. J Biol Chem 268, 7186-7204
71. Tanaka S, Kaytes P, Kurkinen M (1993) An enhancer for transcription of collagen IV genes is activated by F9 cell differentiation. J Biol Chem 268, 8862-8870
72. Quintavalla JC, Berg RA, Beavis AJ, Piccoli SP, Rediske JJ, Kurkinen M, Patrick RA, Roberts FM (1993) Differential induction of stromelysin mRNA by bovine articular chondrocytes treated with interferon-gamma and interleukin-1β. J Cell Physiol 154, 113-121
73. Patel MN, Kurkinen M (1993) Double-reporter vectors for studying bidirectional gene transcription. Biotechniques 15, 615-620
74. Mauviel A, Halcin C, Vasiloudes P, Parks WC, Kurkinen M, Uitto J (1994) Uncoordinated regulation of collagenase, stromelysin and tissue inhibitor of metalloproteinase genes by prostaglandin E2. Selective enhancement of collagenase gene expression in human dermal fibroblasts in culture. J Cell. Biochem 54, 465-472
75. Buttice G, Kurkinen M (1994) Oncogenes control collagenase and stromelysin gene expression. Extracellular Matrix in the Kidney. Contrib Nephrol, Vol. 197 (H. Koide and T. Hayashi, Eds.), Karger, pp 101-107
76. Yang M, Kurkinen M (1994) Different mechanisms of regulation of the human stromelysin and collagenase genes. Analysis by reverse-transcription-coupled-PCR assay. Eur J Biochem 222, 651-658
77. Quinones S, Buttice G, Kurkinen M (1994) Promoter elements in the transcriptional activation of the human stromelysin gene by the inflammatory cytokine, Interleukin-1. Biochem J 302, 471-477
78. Sawai T, Uzuki M, Harris ED Jr, Kurkinen M, Trelstad RI, Hayashi M (1996) In situ hybridization of stromelysin mRNA in the synovial biopsies from rheumatoid arthritis. Tohoku J Exp Med 178, 315-330
79. Benbow U, Buttice G, Nagase H, Kurkinen M (1996) Characterization of the 46-kDa intermediates of matrix metalloproteinase-3 (stromelysin-1) obtained by site-directed mutation of phenylalanine-83. J Biol Chem 271, 10715-10722
80. Ye S, Eriksson P, Hamsten A, Kurkinen M, Humpries SE, Henry AM (1996) Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem 271, 13055-13061
(cited 419 times)
81. Yang M, Hayashi K, Hayashi M, Fuji JT, Kurkinen M (1996) Cloning and developmental expression of a membrane type-matrix metalloproteinase from chicken. J Biol Chem 271, 25548-25554
82. Buttice G, Duterque-Coquillaud M, Basuyaux JP, Carrere S, Kurkinen M, Stehelin D (1996) Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/jun complex. Oncogene 13,, 2297- 2306
83. Gervasi DC, Raz A, Dehem M, Yang M, Kurkinen M, Fridman R (1996) Carbohydrate-mediated regulation of matrix metalloproteinase-2 activation in normal human fibroblasts and fibrosarcoma cells. Biochem Biophys Res Commun 228, 530-538
84. Yang M, Murray MT, Kurkinen M (1997) A novel matrix metalloproteinase gene (XMMP) encoding vitronectin-like motifs is transiently expressed in Xenopus laevis early embryo development. J Biol Chem 272, 13527-13533
85. Yang M, Kurkinen M (1998) Cloning and developmental regulation of tissue inhibitor of metalloproteinase-3 (TIMP3) in Xenopus laevis early embryos. Gene 211, 95-100
86. Yang M, Kurkinen M (1998) Cloning and characterization of a novel matrix metalloproteinase (MMP), CMMP, from chicken embryo fibroblasts. CMMP, Xenopus XMMP and human MMP19 have a conserved unique cysteine in the catalytic domain. J Biol Chem 273, 17893-17900
87. Jayaraman G, Srinivas R, Duggan C, Ferreira E, Swaminathan S, Somasundaram K, Williams J, Hauser C, Kurkinen M, Dhar R, Wetzman S, Buttice G, Thimmapaya B (1999) p300/CBP interactions with Ets-1 and Ets-2 in the transcriptional activation of the human stromelysin promoter. J Biol Chem 274, 17342-17352
88. Olson M, Emblem M, Fecker L, Kurkinen M, Ekblom P (1999) cDNA cloning and embryonic expression of mouse nuclear pore membrane glycoprotein 210 mRNA. Kidney Int 56, 827-838
of note, our paper made the cover as the featured article in Kidney International February 1999 issue
89. Yang M, Kurkinen M (2002) Xenopus XMMP, matrix metalloproteinase-21. Handbook of Proteolytic Enzymes, 2nd Ed (A. Barrett, N. Rawlings and F. Woessner, Eds.) Academic Press, p 132
90. Yang M, Kurkinen M (2002) Chicken CMMP, matrix metalloproteinase-22. Handbook of Proteolytic Enzymes, 2nd Ed (A. Barrett, N. Rawlings and F. Woessner, Eds.) Academic Press, p 133
91. Ye CJ, Stevens JB, Liu G, Bremer SW, Jaiswal AS, Ye KJ, Lin MF, Lawrenson L, Lancaster WD, Kurkinen M, Liao JD, Gairola CG, Shekhar MPV, Narayan S, Miller FR, Heng HHQ (2009) Genome based cell population heterogeneity promotes tumorigenicity: The evolutionary mechanism of cancer. J Cell Physiol 219, 288-300
92. Stevens JB, Abdallah BY, Liu G, Horne SD, Bremer SW, Ye KJ, Huang JY, Kurkinen M, Ye CJ, Hong HHQ (2013) Heterogeneity of cell death. Cytogenet Genome Res 139, 164–173
93. Abdullah BY, Horne SD, Kurkinen M, Stevens JB, Liu G, Ye CJ, Justin Barbat J, Bremer SW, Heng HHQ (2014) Ovarian cancer evolution through stochastic genome alterations: defining the genomic role in ovarian cancer. Syst Biol Reprod Med 60, 2-13
94. Kurkinen M (2015) Kuka Lypsää Lehmät? Fram, Finland. A collection of 47 autobiographical sketches, in Finnish. Original title Who’s Gonna Milk the Cows?
95. Kurkinen M (2017) The amyloid hypothesis is too good to be true. Alzheimers Dement Cogn Neurol 1, 1- 9
96. Kurkinen M (2018) Alzheimer’s dementia drug discovery: targeting astrocyte glutamate uptake. Conn’s Handbook of Models for Human Aging, 2nd Ed (Ronald Conn and Jeffrey Ram, Eds.) Elsevier, pp. 587-591
97. Kurkinen M (2021) Alzheimer’s trials: A cul-de-sac with no end in sight. Adv Clin Exp Med 30, 653-654
98. Kurkinen M, Tran L (2021) Aduhelm: The best hope for Alzheimer’s patients or the worst decision the FDA ever made? J Alzheimers Dis 84, 969-971
99. Kurkinen M (2022) Astrocyte glutamate transporter EAAT2 in Alzheimer dementia. Glutamate and Neuropsychiatric Disorders: Current and Emerging Treatments (Zoran Pavlovic, Ed.) Springer Nature, Berlin, Germany, pp. 229–260
100. Kurkinen M, Fułek M, Fułek K, Beszłej JA, Kurpas D, Leszek J (2023) The amyloid cascade hypothesis in Alzheimer’s disease: should we change our thinking?
Biomolecules 13, 453
101. Kurkinen M (2023) Lecanemab (Leqembi) is not the right drug for patients with Alzheimer’s disease. Adv Clin Exp Med 32, 943–947
102. Kurkinen M (2023) Donanemab: Not two without a third. Adv Clin Exp Med 32, 1085–1087
103. Kurkinen M (2024) Anti-amyloid therapies do not slow Alzheimer’s disease progression. Dementia Neuropsychol 17:e20230099.
104. Daly T, Kurkinen M (2024) Measuring our language about amyloid antibodies in Alzheimer’s disease: technical, theoretical, and lay language considerations.Clin Neurol Neurosurg 241:108314
105. Kurkinen M, Daly T (2024) Survival time in Alzheimer’s disease: an overlooked measure of safety and efficacy of disease-modifying therapies. [published online as ahead of print on October 16, 2024]. Adv Clin Exp Med 2024. doi:10.17219/acem/194003
106. Daly, T, Olluri, A, Kurkinen, M (2025) Anti-amyloid treatments in Alzheimer’s disease: elegance, evidence, and ethics. Adv Clin Exp Med, in press
Appendix 1. Research Activity Including conferences attended, co-organized, invited talks and posters presented, papers, book and grant proposals reviewed
March 11-12, Los Angeles, USA
UCLA workshop: Tools to integrate and plan experiments in neuroscience
one of the 23 attendees, by invitation only by Alcino J. Silva
May 15-16, Lisbon, Portugal
The 11th International Workshop on Computational Systems
Biology (WCSB)
attendee
June 18-21, Vancouver, Canada
International Society for Stem Cell Research (ISSCR)
(not attending) to meet Brigid Hogan, a Presidential Symposium Speaker
July 12-17, Copenhagen, Denmark
Alzheimer’s Association International Conference (AAIC)
poster
Why “amyloid cascade” is a misguided hypothesis of Alzheimer’s dementia etiology?
Markku Kurkinen, Anton Scott Goustin, Jerzy Leszek
poster
Insulin receptors In intact hippocampus and hippocampal cultured cells function downstream of Src-family kinases to protect neurons against excitotoxic glutamate-induced cell death
Anton Scott Goustin, Markku Kurkinen, Thomas Sanderson, ‘Maik Hüttemann
September 15-January 17, 2015, Sabbatical Leave of Absence
Concept development: Astrocyte regulation of synaptic glutamate signaling
c/o Alexej Verkhratsky
University of Manchester, UK
September 29-October 3, Asilomar, USA
27th Annual Mouse Molecular Genetics Conference
attendee
November 15-19, Washington DC, USA
Society for Neuroscience (SfN)
attendee
Kurkinen M (2015) Kuka Lypsää Lehmät? Fram, Vaasa, Finland. 47 short autobiographical stories in Finnish, pp.105. Original title Who’s Gonna Milk the Cows?
February 8-10, Bethesda, USA
NIH Alzheimer’s Disease Research Summit
attendee
March 17-22, Nice, France
Alzheimer’s disease/Parkinson’s disease (AD/PD)
attendee
April 4-6, Washington DC, USA
Alzheimer’s Association Advocacy Forum
attendee
July 18-23, Washington DC, USA
Alzheimer’s Association International Conference (AAIC)
poster
What if Alzheimer dementia is a systemic disease?
Markku Kurkinen, Anton Scott Goustin, Jerzy Leszek, David Woolls
poster
Nanotechnology-based drug delivery systems in Alzheimer’s disease: efficacy of dendrimers
Markku Kurkinen, Barbara Klajnert, Elzbieta Trypka, Jerzy Leszek
September 28-29, Chicheley, Buckinghamshire, UK
Kavli Royal Society meeting on non-coding RNA
attendee
October 13-15, Washington DC, USA
UsAgainstAlzheimer’s National Summit
attendee
October 16-20, Toronto, Canada
World Congress of Psychiatric Genetics (WCPG)
attendee
October 22, Detroit, USA
Graduate Students Research Day
Wayne State University
Member, Judges Committee
November 5-8, Barcelona, Spain
Clinical Trials in Alzheimer’s Disease (CTAD)
attendee
November 22, reviewed and accepted Joe Tsien (2016) Principles of intelligence: On evolutionary logic of the brain. Frontiers in Systems Neuroscience 9:186. doi: 10.3389/fnsys.2015.00186
March 10, reviewed and accepted a book proposal by Jack de la Torre (2016) Alzheimer’s Turning Point. A Vascular Approach to Clinical Prevention. Springer ISBN 768-3-319-34056-2
March 16-21, Lisbon, Portugal
10th World Congress on Controversies in Neurology (CONy)
attendee
April 4-6, Washington DC, USA
Alzheimer’s Association Advocacy Forum
attendee
April 20-25, Budapest, Hungary
Alzheimer’s Disease International (ADI)
attendee
April 31, evaluated and recommended Joe Tsien: A NOVEL APPROACH TO PREDICTING RESILIENCE TO POST-TRAUMATIC STRESS DISORDER.
Proposal:66193LS, U.S. Defense Army Research Project Agency (DARPA)
May 1-4, Auckland, New Zealand
Australia New Zealand Anesthesiology (ANZA)
Perioperative Cognition
attendee
July1-6, Copenhagen, Denmark
10th Federation of European Neuroscience Societies (FENS) Forum
attendee
July 24-28, Toronto, Canada
Alzheimer’s Association International Conference (AAIC)
poster
Is this the Manhattan plot for Alzheimer?
Markku Kurkinen and David Woolls
August 6-7, Oxford, UK
Metalloproteinases and their inhibitors: beginning, past, and future
a meeting to honor G. Murphy and H. Nagase
attendee
September 27-29, Washington DC, USA
UsAgainstAlzheimer’s National Summit
attendee
October 18, Detroit, USA
Graduate Students Research Day
Wayne State University
Member, Judges Committee
November 10-12, San Diego, USA
Molecular and Cellular Cognition Society (MCCS)
attendee
November 12-16, San Diego, USA
Society for Neuroscience (SfN)
attendee
November 13-16, St. Petersburg, USA
American Society for Matrix Biology (ASMB)
attendee
December 8-10, San Diego, USA
Clinical Trials in Alzheimer’s Disease (CTAD)
attendee
2017
Kurkinen M (2017) The amyloid hypothesis is too good to be true. Alzheimer’s, Dementia & Cognitive Neurology 1, online January 31, 2017 DOI:10.15761/ADCN.1000106
February 21-22, San Diego, USA
Alzheimer’s Drug Discovery Foundation (ADDF)
attendee
March 9, Detroit, USA
Wayne State University School of Medicine, Department of Physiology
talk
Alzheimer’s drug discovery: Wo Sind die Magischen Kugeln?
March 27-29, Washington DC, USA
Alzheimer’s Association Advocacy Forum
attendee
April 15, commented on Jack de la Torre: What is wrong with Alzheimer’s research? Journal of Alzheimer’s Disease (Editor’s Blog)
April 26-29, Kyoto, Japan
Alzheimer’s Disease International (ADI)
attendee
May 21-23, Atlanta. USA
Patent Information Users Group (PIUG)
attendee
June 22-24, Copenhagen, Denmark
13th World Federation of Societies of Biological Psychiatry
talk
Alzheimer’s drug discovery: targeting synaptic glutamate uptake
August 27-September 2, Naples-Florence, Italy
Congress on Invertebrate Models of Human Aging
talk
Alzheimer’s drug discovery: targeting synaptic glutamate uptake
September 21-23, Dublin, Ireland
Dementia and Dementia Care
talk (had to cancel)
Alzheimer’s drug discovery: targeting synaptic glutamate uptake
October 13-15, Washington DC, USA
UsAgainstAlzheimer’s National Summit
attendee
October 18, Detroit, USA
Graduate Students Research Day
Wayne State University
Member, Judges Committee
November 2-4, Boston, USA
Clinical trials in Alzheimer’s disease (CTAD)
attendee
Kurkinen M (2018) Alzheimer’s dementia drug discovery: targeting synaptic glutamate uptake. Chapter 44 in Conn’s Handbook of Invertebrate Models of Aging 2nd Ed. (F. Conn and J. Ram, Eds.) Elsevier
February 3-4, Arlington, USA
Alzheimer’s Drug Discovery Foundation (ADDF)
attendee
February 21-23, Paris, France
Vascular Dementia
keynote
Alzheimer’s drug discovery: targeting synaptic glutamate signaling
April 20, reviewed and accepted Aguayo S, Schuh CMAP, Vicente B, Aguayo LG (2018) Association between Alzheimer’s disease and oral and gut microbiota: Are pore forming proteins the missing link? Journal of Alzheimer’s Disease 65, 29-46
June 17-19, Washington DC, USA
Alzheimer’s Association Advocacy Forum
attendee
June 29, accepted invitation to the Scientific Advisory Board of NeuroActiva
July 25-27, Chicago, USA
Alzheimer’s Disease International (ADI)
attendee
September 20, Stockport, UK
The Meadows Hospital
visitor and guest speaker
Alzheimer’s drug discovery and clinical development
September 21-23, Paris, France
Molecular and Cell Science
Organizing member
keynote
Alzheimer’s drug discovery: targeting synaptic glutamate uptake
OF NOTE: the meeting was canceled
September 24-25, London, UK
Dementia and Dementia Care
Organizing member
talk
Alzheimer’s drug discovery: targeting synaptic glutamate uptake
October 4, reviewed and rejected Liu Y, Ward J, Perdomo SJ, Vidoni ED, Sisante JF, Kirkendoll K, Burns JM, Sandra A. Billinger SA. Vascular health predicts amyloid-β in cognitively normal older adults (submitted to Journal of Alzheimer’s Disease)
October 18, Detroit, USA
Graduate Students Research Day
Wayne State University
Member, Judges Committee
November 12, accepted invitation to the Editorial Board of Advances in Geriatric Medicine and Research (AGMR)
December 11, New York, USA
The New York Academy of Sciences
Alzheimer’s Disease Therapeutics: Alternatives to Amyloid
attendee
January 17, invited as Guest Editor to develop a Theme Issue for Frontiers in Molecular Neuroscience: Astrocyte regulation of synaptic glutamate signaling.
(I canceled the project January 28)
January 30, Stockport, UK
Vascular Dementia Conference
talk
Microvascular events in development of dementia
February 18-21, San Francisco, USA
Alzheimer Society International Congress (ASIC)
Co-organizer (with Lloyd Tran) and Co-chair of Program Committee
After 40 years of research failure in Alzheimer’s- Where are we headed?
talk
Alzheimer drugs: targeting synaptic glutamate uptake
February 21-24, Sydney, Australia
7th World Congress of Asian Psychiatry (WCAP)
talk
Alzheimer drugs: targeting synaptic glutamate uptake
August 26, reviewed and accepted Palmer JC, Tayler HM, Dyer L, Kehoe PG, Paton JFR, Love S: Zipotentan: An endothelin A receptor antagonist, prevents Aβ-induced hypertension and maintains cerebral perfusion (submitted to Journal of Alzheimer’s Disease)
October 4, Detroit, USA
Graduate Students Research Day
Wayne State University
Member, Judges Committee
November 29-30, Wroclaw, Poland
13th International Conference of Psychogeriatry 2019: State of Art
talk
Alzheimer’s drugs: targeting synaptic glutamate uptake
April 8, rewieved and accepted Jack de la Torre: Hemodynamic Instability in Heart Failure Intensifies Age-Dependent Cognitive Decline (submitted to Journal of Alzheimer’s Disease)
April 19, rewieved and accepted Gary Riccio*; Rhoda Au; Richard van Emmerik; Mohammed Eslami Situated Precision Health in the Smart Medical Home: II. Bringing NASA’s Metascience Down to Earth (submitted to Advances in Geriatric Medicine and Research)
November 16-18, San Francisco, USA
Alzheimer Society International Congress (ASIC)
Program Co-Chair
talk
Astrocyte glutamate transporter EAAT2 in Alzheimer dementia
December 14-17. Singapore
Alzheimer’s Disease International (ADI)
talk
Alzheimer’s drugs: targeting astrocyte glutamate transporter in synaptic glutamate signaling
Alzheimer’s drug discovery: targeting astrocyte glutamate transporter EAAT2 in synaptic glutamate signaling
© Markku Kurkinen, Wayne State School of Medicine, Center for Molecular Medicine and Genetics, Detroit, Michigan, USA
Abstract
Glutamate is an amino acid and also the major synaptic signaling molecule of neurons, essential in cognition, learning and memory formation. Glutamate is neurotoxic. As soon as the glutamate signaling starts it is stopped in one millisecond by astrocytes, which take up and clear glutamate from synapses. This prevents extended glutamate signaling, loss of synapses and neuron cell death. Astrocytes express EAAT2 (excitatory amino acid transporter-2), the major glutamate transporter and 1% of brain protein. In Alzheimer dementia, astrocytes express less EAAT2. In experimental mouse models of Alzheimer, decreasing EAAT2 expression enhances dementia progression, whereas increasing EAAT2 expression slows dementia progression. To discover drugs, chemical compounds and natural products that can increase astrocyte glutamate uptake, we describe a simple drug screening assay, which targets EAAT2 reconstituted in liposomes, and measures glutamate uptake with red fluorescent Oxonol VI molecule. Most important, by directly targeting the EAAT2 protein in liposomes, our assay should limit off-targeting and adverse events of drugs, which are the main problems in Alzheimer’s drug discovery and clinical development.
Liposome glutamate assay
Glutamate transport by EAAT2 is powered by a transmembrane Na[+] concentration gradient. With every glutamate molecule, three Na[+] ions are co-transported, which make the EAAT2 liposomes more positive-inside. Oxonol VI is a negatively charged lipid soluble red fluorescent molecule, which diffuses in and out of liposomes. When Oxonol VI binds to liposome membrane lipids, its excitation and emission wavelengths increase 10-15 nm. This ‘red shift’ makes it possible to measure Oxonol VI in liposomes by the intensity of red light emitted at 660 nm. Drugs that activate EAAT2 increase glutamate and Na[+] uptake, and in effect, cause more Oxonol VI to stay in liposomes. In other words, the more glutamate in, the more red light out. Liposome glutamate assay is a blind, non-mechanism based assay, easy to do, and cost-effective. Formatted in a high-throughput screening (HTS) platform, drugs, chemical compounds and natural products can be screened in a rather short time.
Principal Investigator is Markku Kurkinen, Professor, Wayne State University School of Medicine, Detroit, USA. Co-Principal Investigators are Hans-Jürgen Apell, Professor Emeritus, University of Konstanz, Germany, and Andrew Fribley, Associate Professor, Wayne State University School of Medicine, Detroit, USA. Collaborators are Olga Boudker, Associate Professor, Cornell University, New York, USA, Niels-Christian Danbolt, Professor, University of Oslo, Norway, Alemu Fite, Research Scientist, Wayne State University School of Medicine, Detroit, USA, Anton Scott Goustin, Research Scientist, Wayne State University School of Medicine, Detroit, USA, Baruch Kanner, Professor, Hebrew University Hadassah Medical School, Jerusalem, Israel, Anna Seelig, Professor Emerita, University of Basel, Switzerland, David Woolls, Research Analyst, Computational Forensic Linguistics (CFL Ltd), Birmingham, UK, and Maozhou Yang, Research Scientist, Henry Ford Hospital, Detroit, USA.
Of note: in my opinion we have onboard some of the best minds on glutamate and EAAT2 (emails of understanding of collaboration on file)
Risto Kurkinen, 65, MA, Co-founder, Project Manager, Graphic designer, Kurkinen Group
Risto Kurkinen, 65, Graphic designer, MA, Kurkinen Group
June 30,1959, Jyväskylä, Finland. Qualified graphic designer in variety fields in graphic design. Courses and studies in 3d, animation, layout and social marketing, photographing. Experience in programs like: Blender, AfterEffects, Adobe CC, Elementor and WordPress. 1982 – 2005 MA-studies in University of Art and Design Helsinki, Finland. From 1986 working in different magazines as art editor and art director. From 1998 experience as art director for companies and organizations.
Risto Kurkinen, MA
Born: June 30, 1959, Jyväskylä, Finland
Citizenship: Finland
Competence
Animation
Brand Strategy
Illustration
Printing technology
Typography
Education
2005 MA, Master of Arts, University of Art and Design Helsinki, Finland
Training
2012 Photographing, Institute of Design and Fine Arts, Lahti, Finland.
2021 Brand Design Masters Academy.
2023 Animation for social media, Keuda, provider of vocational education and training in Järvnepää, Finland.
2024 Social Marketing, Keuda, provider of vocational education and training in Järvenpää, Finland.
Magazine layout
1986 Tekniikan Maailma-magazine
1992 Microbyte-magazine
1996 Reader`s digest-magazine
2008 Kampanja-magazine
2008 Toimisto-magazine
2012 Suomen opettajat-magazine
Book layout
2008 Otava
2010 Reader`s digest
Applied graphic arts
1998 Bus Association
2000 Reader`s Digest
2000 Trade Union of Education, OAJ
2002 Reserve Officer Organization
2003 University of Helsinki Recruiting Center
2008 Zenitel Finland
2010 Marinetek
2012 Päijät-Häme Training Center
Product Manager
2020 Aste Helsinki, Art work preparation and graphics for magazines