FF Principal Investigator/Program Director (Last, first, middle): Larsson, Lars, G.
Provide the following information for the key personnel in the order listed for Form Page 2.
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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
Karolinska Institute, Stockholm (accepted 1971)
Med. candidate 1973 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
1985-1998 Associate Professor (docent) in physiology, Karolinska Institute, Stockholm.
1986-1998 Assistant senior physician (biträdande överläkare), Department of Clinical Neurophysiology, Karolinska
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
1997-2002 (Sept 30) Adjunct Professor the Department of Cell and Molecular Physiology, Hershey Medical School, Penn State
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,
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.
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
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 fasttwitch 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.) 472:595614.
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.) 481:149161.
Larsson, L, Ansved, T. 1995. Effects of aging on the motor unit. Progress in Neurobiology 45: 397458.
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
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
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.
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
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
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