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Michael A. Hill, PhD

Interim Director, Dalton Cardiovascular Research Center
Professor, Department of Medical Pharmacology and Physiology
Office Location: 138 DCRC
Office Phone: 573-884-4601
HillMi@missouri.edu

Research Interests

  • Local control of microvascular hemodynamics
  • Mechanisms underlying the arteriolar myogenic response
  • Mechanotransduction
  • Impact of 3D vascular wall structure on arteriolar function
  • Microvascular dysfunction in experimental diabetes

Research Description

Our laboratory has a principal interest in understanding the signaling mechanisms that underlie the vasoconstrictor response of an arteriole following an acute rise in intraluminal pressure (myogenic response). Broadly speaking this can be considered as a process of mechanotransduction. Our studies have examined the roles of a number of vascular smooth muscle signaling molecules including various kinases and intracellular Ca2+. More recently these studies have been extended to include approaches aimed at determining the relationships between pressure-induced changes in smooth muscle membrane potential, sub-cellular Ca2+ signaling, and the resulting signaling events that ultimately lead to the contractile response.

In addition to basic studies on myogenic signaling we are also studying how myogenic tone interacts with other vasoregulatory mechanisms (principally, endothelial-dependent dilation) and how the myogenic response is altered in diabetes mellitus.

Professional Background

  • Obtained PhD, University of Melbourne.
  • Completed postdoctoral training at Department of Medical Physiology, Texas A&M University.
  • Received Fulbright Fellowship in 1988.
  • Received National Institutes of Health (NIH) FIRST Award in 1992.
  • Obtained past funding from NIH, Juvenile Diabetes Foundation, American Heart Association, National Health and Medical Research Council (Australia); National Heart Foundation (Australia).
  • Acts as a current member of American Heart Foundation (National) grant review panel.
  • Acts as a member of editorial boards of Microcirculation (present), Journal of Vascular Research (present) and American Journal of Physiology (1996-98).
  • Professor of Physiology, School of Medical Sciences, Univeristy of New South Wales, Sydney, Australia, 2006-present
  • Associate Professor, Dep’t of Medicine, St Vincent’s Hospital, University of Melbourne, Melbourne, Australia, 2004-present

Associate Editor:

  • Frontiers in Vascular Physiology (2010 – present)

 

Editorial Boards:

  • American Journal of Physiology: Heart and Circulatory Physiology (1/96 - 12/98)
  • Microcirculation (1/2002 – present)
  • Journal of Vascular Research (2007 – present)
  • Frontiers in Vascular Pharmacology (2010 – present)
  • Frontiers in Vascular Physiology (2010 – present)

Guest Reviewer:

  • American Journal of Physiology -   Heart and Circulation -   Endocrinology -   Cell -  Gastrointestinal Physiology
  • Journal of Biological Chemistry
  • Hypertension
  • Microvascular Research
  • Journal of Applied Physiology
  • Diabetes
  • Journal of Vascular Research
  • Journal of Pharmacology and Experimental Therapeutics
  • Diabetologia
  • Journal of Laboratory and Clinical Medicine
  • Australian and New Zealand Journal of Medicine
  • Biochemica Biophysica Acta
  • British Journal of Pharmacology
  • Clinical and Experimental Physiology and Pharmacology
  • Diabetes Care
  • Journal of Physiology
  • Microcirculation
  • Pflugers Archives
  • Cardiovascular Research
  • FASEB Journal
  • Circulation
  • Expert Opinion on Therapeutic Targets
  • Journal of Vascular Pharmacology
  • Journal of Cellular Physiology
  • Lipids
  • Cell Calcium
  • Circulation Research
  • Canadian Journal of Physiology and Pharmacology
  • Arteriosclerosis, Thrombosis and Vascular Biology
  • Journal of Pharmacy and Pharmacology
  • Journal of Hypertension
  • Vascular Pharmacology
  • PLOS
  • Interface Focus
  • Experimental Biology and Medicine
  • Life Sciences
  • Frontiers in Vascular Pharmacology
  • Frontiers in Vascular Physiology

Grant Reviews:

Study Sections

  • American Heart Association (Virginia ) Peer Review Committee (1992 - 1995), (Chairman, 1995)
  • Member of the Medical Review Board for the Sir Edward Dunlop Medical Research fund (2002 – present).
  • American Heart Association (National; Vascular Wall 1, 2006 – 2009)
  • American Medical Association, 2007.
  • NIH Special Emphasis Panel on Lymphatic Biology, 2009.
  • NIH RFA, Vascular Stiffening and Hypertension, 2010.

Ad Hoc Reviews

  • American Heart Association (Alaska)
  • American Heart Association (Texas)
  • Jeffress Foundation
  • Diabetes Australia Research Trust
  • National Health and Medical Research Council
  • Cardiovascular Lipid Grants (Pfizer)Clive and Vera Ramaciotti Foundation
  • Canadian Heart and Stroke Foundation
  • Australian Research Foundation
  • Wellcome Foundation
  • Louisiana Board of Regents
  • Qatar National Research Foundation
  • National Science Engineering Research Council, Canada

Consultancies/Membership of Boards

Medjaden Bioscience Limited (China), Senior Editor.

Internal Review Panel Member, NIH Program Project Grant, University of Missouri (P.I. Harold Laughlin, Ph.D.), 2007 – 2009.

External Review Panel Member, NIH Program Project Grant, Medical College of Georgia (P.I. R. Clinton Webb, Ph.D.), 2008.

Member of the Executive Board of RDDT (RMIT Drug Design Technologies) (2002 – 2004).

Edward Dunlop Foundation Medical Research Review Board (2002 - present)

Biocomm International (alternate member for Professor David Story; 2001 – 2004)

Rothschilds Bioscience (Review of research submissions, 2000)

National Institutes of Health grant awarded to Luis Martinez-Lemus, PhD Dalton Cardiovascular Research Center, University of Missouri (2009 - 2014).

National Institutes of Health grant awarded to Michael Davis, PhD Department of Medical Physiology, Texas A&M University (1999 - 2004).

National Institutes of Health grant awarded to Gerald Meininger, PhD, Department of Medical Physiology, Texas A&M University (1999 - 2004).

National Institutes of Health grant awarded to Paul Ratz, PhD, Department of Pharmacology, Eastern Virginia Medical School (2001 -2004).

Conference/Symposia Organization

  • Chair of session on Australian and New Zealand Microcirculatory Meeting, Melbourne, 1997.
  • Chair of session on "Arterioles", Australian Physiological and Pharmacological meeting, Brisbane, 1997.
  • Organized symposium on "Microvascular Control Mechanisms" for the Australian and New Zealand Microcirculatory Society Meeting, January 1999, Adelaide.
  • Member of the basic science program committee for the Western Region of the International Diabetes Federation meeting, Sydney 1999.
  • Chair of the Organizing Committee for Australian Physiological and Pharmacological Annual Meeting, Melbourne 2000.
  • Member of the organizing committee for  “Vascular and Neural Complications of Diabetes” – satellite meeting to the International Union of Physiological Societies Meeting, Melbourne, Australia,  2001.Chairperson and organizer of APS symposium for the 2002 Experimental Biology meeting (New Orleans) – “Mechanisms of Vascular Remodeling: Temporal Events From Stimulus to Structural and Functional Changes”.
  • Member of the organizing committee for the 8th International Symposium on Resistance Arteries, France, 2004.
  • Organizer of Symposium on “Role of K+ Channels in Vascular Tone”, Australian Physiological Society, Canberra, August 2005.
  • Chair of the organizing committee for the biannual meeting of the Australian and New Zealand Microcirculatory Society. 2005.
  • Program Committee Member, IEEE Nanomedicine Conference, Macau, August 2007.
  • Chair of the organizing committee for the 9th International Symposium on Resistance Arteries, Hamilton Island, Australia, 2008.
  • Member of the organizing committee for the Microcirculatory Society, 2009 Fall Meeting, University Of Missouri, Columbia, Missouri, September 2009.
  • Organizer/Chair of symposia ‘Interactions Between Smooth Muscle Myosin Light Chain Kinase and Phosphatase in the Regulation of Arteriolar Tone’, Experimental Biology, Anaheim, April, 2010
  • Member of the organizing committee for the 10th International Symposium on Resistance Arteries, Denmark, 2011.

Professional Societies

Microcirculatory Society

American Physiological Society

Australian and New Zealand Microcirculatory Society

Australian Physiological Society

Australian-American Fulbright Alumni

American Association for the Advancement of Science

Committee Memberships:

i.  Intramural

2007 – present             Seminar Committee, Dep’t of Medical Pharmacol. and Physiol.

                                    University of Missouri

2007, 2010                  Local Organizer, University of Missouri Cardiovascular Day

2004 – 2006                School of Medical Science Research Committee (UNSW)

                                    School of Medical Science Space Committee (UNSW)

                                    School of Medical Sciences Executive Committee (UNSW)

2000 – 2003                Chair, Faculty Higher Degrees Committee (RMIT)

                                    Chair, Faculty Research Committee (RMIT)

                                    Faculty International Advisory Sub-committee (RMIT)

1997 – 2003                Faculty Executive (RMIT)

                                    Deans Advisory Committee (RMIT)

                                    Research and Higher Degrees Committee (RMIT)

                                    Faculty Board (RMIT)

ii.  Extramural

2012                            International Committee, American Physiological Society.

2011 – present             President-elect, Microcirculatory Society, USA.

2011 – present             International Liaison Committee, Microcirculatory Society, USA.

2011 – present             Long Range Planning Committee, Chair, Microcirculatory Society, USA.

2010 – present             Steering Committee, CV Section, American Physiological Society

2010 – present             Development Committee, Microcirculatory Society, USA.

2009 – 2012                Nominating Committee, American Physiological Society (CV Section), USA.  Chairperson, 2007 – 2010             

2010 - present             Council Member, Microcirculatory Society, USA.

Selected Publications

Davis, M.J. and Hill, M.A. Signaling mechanisms underlying the vascular myogenic response. Physiological Reviews 79:387-423, 1999.

Zou, H., Ratz, P.H. and Hill, M.A. Temporal aspects of [Ca2+]i and myosin phosphorylation during myogenic and agonist-induced arteriolar constriction. J. Vasc. Res. 37:556-567, 2000.

Murphy, T.V., Spurrell, B.E. and Hill, M.A. Tyrosine kinase activity following alterations in intraluminal pressure and wall tension in rat cremaster arterioles. Am. J. Physiol. 281:H1047-H1056, 2001.

Hill, M.A.,Zou, H., Potocnik, S.J., Meininger, G.A. and Davis, M.J. Arteriolar smooth muscle mechanotransduction: Ca2+ signaling underlying myogenic reactivity.J. App. Physiol.91:973-983, 2001.

Bishara, N., Dunlop, M.E., Murphy, T.V., Darby, I.A., Rajanayagam, M.A.S.and Hill, M.A. Matrix protein glycation impairs agonist-induced intracellular Ca2+ signaling in endothelial cells. J. Cell Physiol. 193:80-92, 2002. January 28, 2008

Hill, M.A.Increased intraluminal pressure stimulates MAP kinase phosphorylation in arterioles: dissociation from the acute myogenic contractile response.Am. J. Physiol.285:H1764-73, 2003.

Martinez-Lemus, L.A., Hill, M.A., Bolz, S.S., Pohl, U. and Meininger, G.A. Vascular Smooth Muscle Cell Slipping and Creeping: An acute form of vascular remodeling. FASEB J. 18:708-10, 2004.

Kotecha, N. and Hill, M.A. Arteriolar smooth muscle membrane potential and Ca2+i supply during myogenic contraction of skeletal muscle arterioles. Am. J. Physiol. 289:H1326-1334, 2005.

Bishara, N.V., Triggle, C.R. and Hill, M.A. Relationship between store-operated and arachidonic acid sensitive Ca2+ entry in endothelial cells. Endothelium 12:153-161, 2005.

Hill, M.A.,Davis, M.J., Meininger, G.A., Potocnik, S.J. and Murphy, T.V. Arteriolar myogenic signalling mechanisms: Implications for local vascular function.Clin. Haemorrheol. Microcirc.34:67-79, 2006.

McSherry, I. N., Sandow, S. L., Campbell, W. B., Falck, J. R., Hill, M. A. and Dora, K. A. A role for heterocellular coupling and EETs in dilation of rat cremaster arteries. Microcirculation 13:119-130, 2006.

Potocnik, S.J., Jenkins, N., Murphy, T.V. and Hill, M.A. Membrane cholesterol depletion with b-cyclodextrin impairs calcium signalling and pressure-induced contraction in isolated skeletal muscle arterioles. J. Vasc. Res.44:292-302, 2007.

Murphy, T.V., Kotecha, N. Hill, M.A. Endothelium-independent constriction of isolated, pressurized arterioles by Nw-nitro-L-arginine methyl ester (L-NAME). Br. J. Pharmacol. 151:602-609, 2007.

Hill, M.A., Sun, Z., Martinez-Lemus, L. and Meininger, G.A. Novel imaging approaches provide a driving force to advance the field of arteriolar and vascular cell mechanotransduction.Trends in Pharmacol. Sci.28:308-315, 2007.

Hill, M.A. and Davis, M.J. Coupling a Change in Intraluminal Pressure to Vascular Smooth Muscle Depolarization: Still Stretching for an Explanation. (Editorial Focus) Am. J. Physiol. 292:H2570-H2572, 2007.

Kockx, M., Guo, D.L., Kay, J., Saba, M., Jary, E., Hill, M.A., Gaus, K., Stow, J., Jessup, W. and Kritharides, L. Secretion of apolipopotein E from human macrophages occurs via a protein kinase A- and calcium-dependent pathway along the microtubule network. Circ. Res. 101:607-616, 2007.

Davis, M.J., Hill, M.A. and Kuo, L. Regulation of Microvascular Blood Flow, in Microcirculation, Handbook of Physiology (2nd Edition), Eds Tuma, Duran and Ley, Academic Press, 2008, Ch 6, pp161 – 285.

Raina, H., Ella, S.R. and Hill, M.A. Decreased expression of the smooth muscle Na+/Ca2+ exchanger impairs arteriolar myogenic reactivity. J. Physiol. 586:1669-1681, 2008.

Young, E.J., Hill, M.A., Wiehler, W.B., Triggle, C.R., and Reid, J.J. Reduced EDHF responses and connexin activity in mesenteric arteries from the insulin-resistant obese Zucker rat. Diabetologia 51:872-881, 2008.

Sun, Z., Martinez-Lemus, L.A., Hill, M.A. and Meininger, G.A. Extracellular matrix specific focal adhesions in vascular smooth muscle produce mechanically active adhesion sites. Am. J. Physiol. Cell Physiol. 295:C268-C278, 2008.

Sheng, J-Z, Ella, S.R., Davis, M.J., Hill, M.A. and Andrew P. Braun Openers of small and intermediate-conductance, Ca2+-activated K+ channels enhance agonist-evoked endothelial nitric oxide synthesis and vasodilation of rat cremaster arterioles. FASEB J. In Press (Nov), 2008.

Martinez-Lemus, L., Hill, M.A. and Meininger, G.A., The plastic nature of the vascular wall: a continuum of remodeling events contributing to control of arteriolar diameter and structure. Physiology 24:45-57, 2009.

Hill, M.A., Meininger, G.A., Davis, M.J. and Laher, I. Trends Pharmacol. Sci. Therapeutic potential of targeting arteriolar myogenic tone. 30:363-374, 2009.

Hill, M.A., Yang, Y., Ella, S.R. and Davis, M.J. Large conductance, Ca2+-activated K+ channels (BKCa) and arteriolar myogenic signaling. FEBS Lett (Invited review). 584:2033-2042, 2010.

Potocnik, S.J., McSherry, I., Ding, H., Murphy, T.V., Kotecha, N., Dora, K.A., Triggle, C.R. and Hill, M.A. Endothelium-dependent vasodilatation in myogenically-active mouse skeletal muscle arterioles: role of EDHF and K+ channels. Microcirculation. 8:1-14, 2009.

Yang, Y., Murphy, T.V., Ella, S.R., Haddock, R., Hwang, Y.T., Grayson, T.H., Braun, A.P., Gui, P., Davis, M.J. and Hill. M.A. Heterogeneity in function of small artery smooth muscle BKCa: Involvement of the b-subunit. J. Physiol., 587:3025-3044, 2009. PMID: 19359368.

Zuidema MY, Yang Y, Wang M, Kalogeris T, Liu Y, Meininger CJ, Hill MA, Davis MJ, Korthuis RJ. Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BKCa channels. American Journal of Physiology (Heart and Circulation) 299:H1554-67, 2010.

Ella, S.R., Clifford, P., Yang, Y., Dora, K.A., Meininger, G.A., Davis, M.J. and Hill, M.A. Use of FRET for measurement of changes in membrane potential in arteriolar vascular cells. Microcirculation. 17:629-640, 2010.

Jackson T.Y., Sun, Z., Martinez-Lemus, L.A., Hill, M.A. and Meininger, G.A. Cadherins play a role in arteriolar myogenic responsiveness. Frontiers in Vascular Physiol 1:165-172, 2010.

Yu, X., Stavrakis, S., Huang, S., Patterson, E., Hill, M.A., Hamlett, S., Lazarra, R., Cunningham, M.W. and Kem, D.C. Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" postural hypotension. Hypertension (Under Revision)

Liu, Y., Kalogeris, T., Wang, M., Zuidema, M., Wang, Q., Dai, H., Davis, M.J., Hill, M.A. and Korthuis, R.J. Hydrogen sulfide preconditioning or neutrophil depletion attenuates ischemia/reperfusion-induced mitochondrial dysfunction in rat small intestine. (Under revision, Am. J. Physiol.).

Clifford. P.S., Ella, S.R., Yang, Y., Davis, M.J., Meininger, G.A. and Hill, M.A. Spatial distribution and mechanical function of elastin in resistance arteries - a role in bearing longitudinal stress. (ATVB, submitted).

Martinez-Lemus, L.A., Meininger, G.A., Hill, M.A. and Pohl, U. The structural characteristics of small resistance arteries. Basic& Clin Pharmacol & Toxicol.


Published by Dalton Cardiovascular Research Center, 134 Research Park Dr., Columbia, MO 65211
Phone: 573-882-7588 | Fax: 573-884-4232 | Email: dalton@missouri.edu