|
|
Mark K. Larson, Ph.D. |
Education and Training:
2004-2006
Postdoctoral fellow, Centre for Cardiovascular Sciences
University of Birmingham
Birmingham, United Kingdom
Dr. Steve Watson, mentor1998-2003
Ph.D. in Pharmacology
University of North Carolina at Chapel Hill
Dr. Leslie V. Parise, mentor1994-1998
B.A. in Biology and Chemistry
Concordia College
Moorhead , Minnesota
Teaching at Augustana College:
Cell Biology
Pharmacology
Biochemistry
Introductory Biology
Research Interests:
1) The population of our blood cells is largely derived from hemtopoietic stem cells found within the bone marrow. Since the blood cells turn over at a relatively rapid rate, these progenitor cells are in constant demand to repopulate the vasculature. As such, the stem cells are receptive to stimuli that promote a shift from a state of cellular proliferation to one of differentiation. Platelets are derived from cells called megakaryocytes, and in the process of producing platelets, megakaryocytes form long filamentous branches called proplatelets. The tips of these proplatelets are the site of platelet assembly and packaging.
Though the existence of proplatelets has been known for at least 100 years, it is only recently that the mechanisms that underlie proplatelet structure and function have been examined. The aim of my work is to elucidate some of the extracellular signals that influence proplatelet formation, and to also identify some of the intracellular changes that are part of platelet genesis within the megakaryocyte.
Mouse megakarocyte forming proplatelets
2) Platelets are a critical component in maintaining normal hemostasis for over 1,000 square meters of vascular area throughout the human body. Over one trillion platelets circulate in the blood with a singular purpose: to be the first line of defense in repairing vascular damage. Vascular damage results in the release of platelet agonists that rapidly convert the platelet from a resting state to an active conformation, made evident by numerous dramatic changes to the platelet itself. This activation ultimately leads to aggregation, a key component of wound healing.
I am currently involved in a collaborative project with Dr. Bill Harris at the Sanford School of Medicine in analyzing the effects of omega-3 fatty acid intake on platelet function. We are interested in how the fatty acids affect platelet aggregation, secretion, and spreading. We hope to determine if omega-3's can be a potential defense against cardiovascular disease.
Platelets defective in the small GTPases Rac1 and Rac2 show defects in their
ability to spreak upon the matrix protein fibrinogen.
(From McCarty, Larson, e tal., J. Biol. Chem. 280: 39474-39484, 2005)
Publications:
Dhanjal, T.S., Pendaries, C., Ross, E.A., Larson, M.K. , Protty, M.B., Buckley, C. D., and Watson, S.P. A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice. Blood. 109:4237-4244, 2007.
Larson, M. K. , and Watson, S. P. Regulation of proplatelet formation and platelet release by integrin αIIbβ3. Blood . 108:1509-1514, 2006.
Larson, M. K. , and Watson, S. P. A product of their environment: do megakaryocytes rely on extracellular cues for proplatelet formation? Platelets . 17:435-440, 2006.
Yuan, W., McFadden, A.W., Wang, Z., Larson, M. K. , Boudignon-Proudhon, C., and Parise. L.V. CIB is an endogenous inhibitor of inside-out integrin αIIbβ3 activation in primary murine megakaryocytes. J. Cell. Biol. 172:169-175, 2006.
McCarty, O.J.T., Larson, M.K. , Auger, J.M., Kalia, N., Atkinson, B.T., Pearce, A.C., Ruf, S., Henderson , R.B., Tybulewicz, V.L.J., Machesky, L.M., and Watson, S.P. Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow. J. Biol. Chem . 280: 39474-39484, 2005.
Holly, S.P., Larson, M.K. and Parise, L.V. The unique N-terminus of R-ras is required for Rac activation and precise regulation of cell migration. Mol. Biol. Cell 16:2458-2469, 2005.
Larson, M.K. , Chen, H., Kahn, M.L., Taylor , A.M., Fabre, J.-E., Mortensen, R.M., Conley, P.B., and Parise, L.V. Identification of P2Y 12 -dependent and independent mechanisms of glycoprotein VI-mediated Rap1 activation in platelets. Blood 101:1409-1415, 2003.
Holly, S.P., Larson, M.K. , and Parise, L.V. Multiple roles of integrins in cell motility. Exp. Cell Res. 261:69-74, 2000.
Aho, E.L., Botten, J.W., Hall, R.J., Larson, M.K. , and Ness , J.K. Characterization of a class II pilin expression locus from Neisseria meningitidis : evidence for increased diversity among pilin genes in pathogenic Neisseria species. Infect. Immun . 65:2613-2620, 1997.
Invited Talks :
Larson, M.K. Megakaryocytes to platelets: cutting big cells down to size. Biology Department seminar, April 2007, Sioux Falls , SD.
Larson, M.K. and Watson, S.P. Differential contribution of extracellular matrix proteins in proplatelet development. Oral presentation, Irish-UK Platelet Conference, September, 2005, Dublin , Ireland .
Larson, M. K. , Wang, Z., McFadden, A.W., Yuan, W., Chrzanowska-Wodnicka, M., White, II, G. C., and Parise, L.V. Evidence for Rap1-induced activation of the a 2 b 1 integrin in murine megakaryocytes. Oral presentation, The American Society of Hematology Annual Meeting, December 2003, San Diego , California .
Larson, M.K. Mapping platelet responses to collegen: The importance of a little rap. Invited seminars, Augustana College , Sioux Falls , SD , and Concordia College , Moorhead , MN , October 2002.
Larson, M. K. , Chen, H., Kahn, M.L., Fabre, J.-E., Koller, B. H., and Parise, L.V. Critical role for the ADP receptor, P2Y 12 , in GPVI-mediated activation of Rap1b in platelets. Oral presentation, The American Society of Hematology Annual Meeting, December 2001, Orlando , Florida .
Selected Poster Presentations:
Larson, M.K. and Watson, S.P. Differential effects of extracellular matrix proteins on proplatelet formation: A novel role for fibrinogen. Poster presentation, The American Society of Hematology Annual Meeting, December 2005, Atlanta , Georgia .
Larson, M.K. and Watson S.P. Evaluation of the mechanisms of proplatelet formation on fibrinogen. Poster presentation, Gordon Research Conference on the Cell Biology of Megakaryocytes and Platelets, March 2005, Santa Barbara , CA .
Larson, M. K. and Watson, S. P. Intracellular Ca ++ mobilization is necessary and sufficient for rapid talin translocation to the platelet periphery. Poster presentation, U.K.-Japan Platelet Conference, September 2004, Oxford , United Kingdom .
Trotter, K.W., Larson, M. K. , Kandasamy, R., Boucher, R.C., Stutts, M. J., and Milgram, S. L. The characterization of A-kinase anchoring proteins in airway epithelia: implications for the control of CFTR channel activity. Poster presentation, American Society for Cell Biology Annual Conference, December 1997, Washington , D.C.
Comments? Questions? Please contact steven.matzner@augie.edu
Last modified:
