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  • 1. FF Principal Investigator/Program Director (Last, first, middle):      Larsson, Lars, G. BIOGRAPHICAL SKETCH Provide the following information for the key personnel in the order listed for Form Page 2. Photocopy this page or follow this format for each person. NAME POSITION TITLE Larsson, Lars Marie Underhill Noll Preofessor in Physiology and Clinical Neurophysiology EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY (if applicable) Karolinska Institute, Stockholm (accepted 1971) Medical 1973 Medicine Med. candidate 1973 Candidate Medicine Department of Physiology, Karolinska Institute Ph.D. 1978 Physiology Ph.D. 1978 Physiology Karolinska Institute, Stockholm M.D. 1982 Medicine Karolinska Institute, Stockholm Specialist 1985 Clin. Neurophysiology                         RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding with present position, list, in chronological order, previous employment, experience, and honors. Include present membership on any Federal Government public advisory committee. List, in chronological order, the titles, all authors, and complete references to all publications during the past three years and to representative earlier publications pertinent to this application. If the list of publications in the last three years exceeds two pages, select the most pertinent publications. DO NOT EXCEED 3 PAGES. 1975-1976 Temporary M.D. appointment as orthopedic surgeon, Linköing hospital, Södersjukhuset 1973-1977 Research assistant, Department of Physiology III , Karolinska Institute, Stockholm. 1977-1978 Research assistant, Laboratory of Human Performance, National Defense Research Institute, Stockholm. 1978 (Oct. Dec.) Post-Doctoral Student Biomechanical Laboratory, Penn State University, Pennsylvania, USA. 1979-1982 Research assistant, Department of Physiology III (neurophysiology), Karolinska Institute, Stockholm. 1982-1985 Specialist education (FV block) at the Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm. 1985 Granted the qualification as a specialist in clinical neurophysiology by the National Swedish Board of Health and Welfare. 1985-1998 Associate Professor (docent) in physiology, Karolinska Institute, Stockholm. 1986-1998 Assistant senior physician (biträdande överläkare), Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm. 1988 (Nov. -Dec.) Visiting scientist, Padova University, Italy. 1991(Aug.) -1992(Sept.) VisitingProfessor, Dept. of Physiology, School of Medicine, University of Wisconsin-Madison, WI, USA. 1997-2002 (Sept 30) Marie Underhill Noll Professor the Noll Physiological Research Center, The Pennsylvania State University, USA 1997-2002 (Sept 30) Adjunct Professor the Department of Cell and Molecular Physiology, Hershey Medical School, Penn State University, USA 1997-2000 Director, General Clinical Research Center, University Park, The Pennsylvania State University 1998-2002 (Sept 30) Endowed Professor, The Pennsylvania State University 1999-present Adjunct Professor, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden 2001-2002 (Sept) Interim Director, Noll Physiological Research Center, The Pennsylvania State University.. 2002 (Sept)-present Professor & Chair, Department of Clinical Neurophysiology, Academic Hospital, Uppsala University, Uppsala, Sweden 2002 (Oct 1)-present Research Professor, Center for Developmental & Health Genetics, The Pennsylvania State University Selected publications prior to 2000: Larsson L. 1978. Morphological and functional characteristics of the aging skeletal muscle in man. A cross-sectional study. Acta Physiol Scand Suppl 457 Larsson, L. Grimby, G., Karlsson, J. 1979. Muscle strength and speed of movement in relation to age and muscle morphology.
  • 2. J Appl Physiol 46:451-456 Larsson, L. 1982. Aging in mammalian skeletal muscles. In: The aging Motor System. Advances in Neurogerontology. Vol 3. 45, 397-458 eds Mortimer, J.A., Pirozzolo, F.J., Maletta, G.J. Praeger, New York. 60-90. Larsson, L. 1983. Histochemical characteristics of human skeletal muscle during aging. Acta Physiol Scand 117:469-471. Larsson, L, Edström, L. 1986 Effects of age on enzyme-histochemical fibre spectra and contractile properties of fast- and slow- twitch skeletal muscles in the rat. J Neurol Sci 76:69-89 Edström, L, Larsson, L. 1987. Effects of age on muscle fibre characteristics of fast- and slow-twitch single motor units in the rat. J Physiol (Lond.) 392:129-145 Larsson, L, Ansved, T. 1988. Effects of age on the motor unit. A study on single motor units in the rat. Ann New York Acad Sci 515:303-313. Larsson, L, Salviati, G. 1989. Effects of age on calcium transport activity of sarcoplasmic reticulum in fast- and slow-twitch rat muscle fibres. J Physiol (Lond.) 419:253-264. Lännergren, J., Larsson, L., Westerblad, H. 1989. A novel type of delayed tension reduction found in rat motor units after intense activity. J Physiol (Lond.) 412:267-276. Ansved, T., Larsson, L. 1989. The effects of age on contractile, morphometrical and enzyme-histochemical properties of the rat soleus muscle. J Neurol Sci 93:105-124. Ansved, T., Larsson, L. 1990. Quantitative and qualitative morphological properties of the soleus motor nerve and the L5 ventral root in young and old rats. Relation to number of soleus muscle fibres. J Neurol Sci 96:269-282. Ansved, T., Wallner, P., Larsson, L. 1991. Spatial distribution of motor unit fibres in fast- and slow-twitch rat muscles with special reference to age. Acta Physiol Scand 143:345-354. Larsson, L, Ansved, T., Edström, L., Gorza, L. Schiaffino, S. 1991. Effects of age on physiological, immunocytochemical and biochemical properties of fastbtwitch single motor units in the rat. J Physiol (Lond) 443:257-275. Larsson, L., Edström, L., Lindegren, B., Gorza, L, Schiaffino, S. 1991. MHC composition and enzyme-histochemical and physiological properties of a novel fast-twitch motor unit type. Am J Physiol (Cell Physiol) 261:C93-C101. Larsson, L. 1992. Is the motor unit uniform? Acta Physiol Scand 144:143-154 Larsson, L, Moss R.L. 1993. Maximal velocity of shortening in relation to myosin isoform composition in single fibres from human skeletal muscles. J Physiol (Lond.) 472:5954614. Larsson, L, Li, X., Teresi, A., Salviati, G. 1994. Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats. J Physiol (Lond.) 481:1494161. Larsson, L, Ansved, T. 1995. Effects of aging on the motor unit. Progress in Neurobiology 45: 397 458. Larsson, L, Li, X., Tollback, A., Grimby, L. 1995. Contractile properties in single muscle fibres from chronically overused motor units in relation to motoneuron firing properties in prior polio patients. J Neurol Sci 132:182-192 Larsson, L, Li, X., Berg, H., Frontera, W. 1996. Effects of removal of weight-bearing function on contractility and myosin isoform composition in single human skeletal muscle cells. Pflügers Archives, Europ J Physiol 432:320-328. Li, X, Larsson, L. 1996. Maximum shortening velocity and myosin isoforms in single fibers from young and old rats. Am J Physiol (Cell Physiol) 270: C352-C360. Li, X., Huges, S.M., Salviati, G., Teresi, A., Larsson, L. 1996. Effects of thyroid hormone treatment on contractile properties and myosin isoform composition in single soleus fibres from young and old rats. J Physiology (Lond.) 494:555-567. Larsson, L, Li, X., Frontera, W.R. 1997. Effects of aging on shortening velocity and myosin isoform composition in single fibres from man. Am J Physiol (Cell Physiology) 272 41:C638-C649 Li, X., Larsson, L. 1997. Contractility and myosin isoform compositions of skeletal muscles and muscle cells from rats treated with thyroid hormone for 0, 4 and 8 weeks. J Muscle Res Cell Mot 18:1-10 Yu, F., Degens, H., Li, X., Larsson, L. 1998 Effects of thyroid hormone, gender and age on contractility and myosin composition in single rat soleus fibres. Pflugers Archives. 437:21-30. Höök, P., Li, X., Sleep, J., Hughes, S.M., Larsson, L. 1999. Motility of slow myosin extracted from single muscle cells in young and old rat soleus muscle. J Physiol (Lond.) 520:463-471. Larsson, L., Höök, P., Pircher, P. 1999. Regulation of human muscle contraction at the cellular and molecular levels. Ital J Neurol 20:413-422. All publications 2000-2003: Larsson, L, Li, X., Edström, L., Eriksson, L.I., Zackrisson, H., Argentini, C., Schiaffino, S. 2000. Loss of muscle myosin and acute quadriplegia in patients treated with non-depolarizing neuromuscular blocking agents and corticosteroids. Underlying cellular and molecular mechanisms. Critical Care Medicine 28:34-45 Chomez, P., Neveu, I., Mansén, A., Larsson, L, Arenas, E, Vennström, B. 2000. Delayed cerebellum development in mice lacking the rev-erb Alpha orphan receptor. Development 127:1489-1498 Yu, F., Goethe, S., Vennström, B., Larsson, L. 2000. Effects of thyroid hormone gene disruption by homologous recombination on myosin expression in mouse skeletal muscle. Am J Physiol 278: R1545-R1554. Höök, P., Larsson, L. 2000. A novel in vitro motility assay to study different myosin isoforms extracted from single muscle fiber
  • 3. segments. Effects of temperature, direction of motility and myosin concentration. J Muscle Res Cell Mot. 21:357-365. Larsson, L., Ramamurty, B. 2000. Aging-related changes in skeletal muscle function. Drugs & Aging 17:303-316. Höök, P., Sriramoju, V., Larsson, L. 2001. Effects of aging on actin sliding speed on myosin from single mouse, rat and human skeletal muscle cells. Am J Physiol:Cell. 280: C782-C788. Larsson, L., Höök, P., Yu, F., Marx, J., Pircher,. P. 2001. Effects of aging on regulation of muscle contraction at the motor unit, muscle cell, and molecular level. Invited review. Int. J of Sport Nut Exerc Metab 11:S28-S43 Ramamurthy, B., Höök, P., Jones, D.A., Larsson, L. 2001.Changes in myosin structure and function in response to glycation. FASEB J. 15: 2415-2422 Mansén, A., Yu, F. Larsson, L., Vennström, B. 2001. Differential roles of thyroid hormone receptors α 1, α1/β and β in hormone dependent repression of the β/slow MyHC isoform in the myocardium. Molecular Endocrinology. 15:2106-2114. Marx,J.O., Kraemer, W.J., Nindl, B.C., Larsson, L. 2002. The effect of aging on skeletal muscle myosin heavy chain mRNA. J Gerontology: Biol Sci 1. 57A:B1-B7. Vallaincourt, D.E., Larsson, L., Newell, K.M. 2002. 1Time dependent structure in the discharge rate of human motor units. Clinical Neurophysiology 113:1325-1338. Yu, F., Ståhl, P., Thornell, L.-E., Larsson, L. 2002. Unique expression of myosin heavy chain and myosin binding protein C isoforms isoforms in single muscle cells from human masticatory muscles. Journal of Muscle research and Cell Motility. 123:317-326 Gur, H., Gransberg, L., VanDyke, D., Larsson, L. 2003. Relationship between in vivo muscle force at different speeds of movement and myosin isoform expression in men and women. European Journal of Applied Physiology 88:487-496. Vaillancourt, D.E., Larsson, L., Newell, K.M. 2003 Force variability, single motor unit discharge patterns, and structure of 10, 20, and 40 Hz EMG activity in older adults. 1Neurobiology of Aging 24:25-35 Ramamurthy, B., Jones, A.D., Larsson, L. 2003. Glutathione reverses early effects of glycation on myosin function. American Journal of Physiology:Cell 285:C419-424. Larsson, L. 2003. Effects of Aging on Motor Unit Structure and Function. In: Handbook of Clinical Neurophysiology. Ed: E. Stålberg. Contraction in Human Muscle Cells. In press. Lionikas, A., Blizzard, D., Vogler, G., McClearn, G.E., Larsson, L. 2003. Genetic Architecture of Fast- and Slow-Twitch Muscle Weight in 200-day Old Mice of the C56BL/6J and DBA/2J Lineage. Physiological Genomics In press. Research projects ongoing or completed during the past 3 years (annual direct costs): AR47318 07/01/01-06/30/03 ($250,000) NIAMS R01 (PI: Larsson) Shortening velocity and scaling: Underlying mechanisms Mechanisms underlying the altered contractile speed in muscle cells expressing different myosin isoforms in mammalian species with a large variation in body size. AR45627 08/01/00-07/31/03 ($250,000) NIAMS R01 (PI: Larsson) Sarcopenia: Underlying Mechanisms Cellular and molecular mechanisms underlying the aging-related decrease in force and contractile speed in humans. No number 1/1/2000-12/31/2002 ($52,000) Muscular Dystrophy Association (PI: Larsson) Thyroid Hormone Regulation of Myosin Synthesis Effects of altered thyroid hormone levels and thyroid hormone nuclear receptor deficiency on the expression of myofibrillar protein synthesis. QOL-2000-6.2 01/01/01-12/31/03 ($72,000) European Commisssion Program project (PI: Hughes $620,000;, Co-I: Larsson) Age-related muscle wasting: causes, prevention and reversal Mechanisms underlying the aging-related muscle wasting in experimental animal studies at the gene, molecular and cellular levels. AG014731 10/1/02-9/30/04 ($200,000) NIA (competitive supplement to P01, G. McClearn PI: $1,060,469) (Supplement PI: Larsson) QTL Analysis of Age-Related Phenotypes QTL analysis of sarcopenia
  • 4. K99-12X-08651 7/1/85-12/31/05 ($42,500) The Swedish Research Council (PI: Larsson) Regulatory and Modulatory Influence of Myosin and Myosin Associated Protein Isoforms on Muscle Contraction Regulation and modulation of myosin heavy and light chain, myosin binding protein C, and regulatory protein isoforms on contractile speed at the cellular and molecular levels. BMH4-CT96-0174 6/1/1996-5/31/1999 (completed) European Commission Program Project( PI: Larsson) The Age-related Motor handicap: Basic and Clinical Studies of Skeletal muscle