Dr Scott Levick

Associate Professor, George and Mary Thompson Research Fellow

Telephone 99264911

Curriculum vitae Curriculum vitae

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Biographical details

Dr. Levick completed his PhD in Biomedical Sciences at the University of Queensland in 2005. From there he completed a postdoctoral fellowship at the University of South Carolina School of Medicine in the United States (2005-2011). He then moved to a faculty position at the Medical College of Wisconsin in 2011 as an Assistant Professor of Pharmacology and Toxicology, as well as being a member of the Cardiovascular Research Center (2011-2017). In 2017 he was promoted to Associate Professor at the Medical College of Wisconsin before moving to the Kolling Institute for Medical Research/University of Sydney as an Associate Professor and George and Mary Thomson Research Fellow.

Research interests

My laboratory is interested in the mechanisms that underlie adverse cardiac remodelling leading to heart failure. We are particularly focused on cardiac fibrosis, a condition of excess extracellular matrix production in the heart that has important consequences for heart function. Current projects involve investigations into the contribution of neuropeptides and inflammatory cell in this process.

Current projects

Pro-Fibrotic Effects of Substance P and the Neurokinin-1 Receptor:

We have established that the sensory nerve neuropeptide substance P (SP) is critical to the development of fibrosis in the heart under conditions of pressure overload (e.g. hypertension). This does not appear to be via direct effects on cardiac fibroblasts, the major extracellular matrix producing cells in the heart. Thus, additional intermediate steps must be involved. This project investigates the role of macrophages in mediating the pro-fibrotic actions of SP. This includes mice with macrophage-specific deletion of the neurokinin-1 receptor (NK-1R, receptor for SP), primary cell and cell line cultures, and investigation of macrophage phenotype using flow cytometry.

Protection From Diabetic Cardiomyopathy by Substance P:

Whilst increased substance P (SP) promotes fibrosis in the pressure overloaded heart, a loss of SP leads to fibrosis in the diabteic heart. We found that exogenous restoration of SP reverses this fibrosis. We have data indicating that this is through direct effects on cardiac fibroblasts. This project will investigate the neurokinin receptor mediating the protective actions of SP, and will identify the cellular and molecular mechanisms activated by SP within the cardiac fibroblast.

Mast Cells as Mediators of Cardiac Fibrosis:

Evidence from our laboratory as well as others has demonstrated the importance of mast cells in the development of cardiac fibrosis. These pro-fibrotic actions are mediated through the release of mast cell-specific proteases such as tryptase and chymase. However, the stimuli that activate cardiac mast cells in vivo are not known. This project makes use of mast cell-deficient mice reconstituted with mast cells with genes for specific receptors deleted in an attempt to identify activating stimuli. This project will also investigate the contribution to fibrosis by non-protease molecules released by mast cells.

Dual Roles for Neurokinin-1 Receptors in Ischaemia Reperfusion Injury:

We believe that the neurokinin-1 receptor (NK-1R) provides protection from cardiomyocyte death in the infarct region acutely following ischaemia, whilst chronic activation of the NK-1R promotes cardiomyocyte hypertrophy and cardiac fibrosis in the non-infarcted region of the heart. It is our hypothesis that these divergent temporal responses are mediated by two isoforms of the NK-1R, with the full length isoform providing protection and the truncated isoform driving hypertrophy and fibrosis. This project uses cell-specific deletion of the NK-1R to investigate the role of this receptor in cardiomyocyte survival, hypertrophy, and cardaic fibrosis. In vitro cardiomyocyte cultures will be used to identify the contribution of each NK-1R isoform to survival and hypertrophy.

Associations

Fellow of the American Heart Association

American Physiological Society

Awards and honours

2001 Bachelor of Applied Science, First Class Honors, University of Queensland

2001 Vacation Scholarship, Australian National Heart Association

2002 - 2005 Australian Postgraduate Scholarship

2004 Faculty of Biological and Chemical Sciences Travel Award, University of Queensland

2005 Dean's Commendation Awarded for PhD Dissertation, University of Queensland

2007 - 2008 Philip Morris External Research Program Postdoctoral Fellowship Award, Philip Morris International

2007 Postdoctoral Teacher Training Program Award, National Science Foundation-Experimental Program to Stimulate Competitive Research (EPSCoR)

2008 - 2010 American Heart Association Postdoctoral Fellowship

2009 The American Physiological Society (APS) Cardiovascular Section Research Award for Meritorious Research by a Young Investigator

2012 Competitively selected as Medical College of Wisconsin's Representative to Apply to the Searle Scholars Program

2014 Eric Olsen Oration Finalist at the 2nd Cardiovascular Forum for Promoting Centers of Excellence and Young Investigators, International Academy of Cardiovascular Sciences, Winnipeg, Canada

2014 Outstanding Medical Student Teacher Award - Physician Scientist Pathway

2015-2017 Medical College of Wisconsin Presidential Faculty Scholar Award

2016 Outstanding Medical Student Teacher – M2 Gastrointestinal Nutrition Unit

2016 Elected Fellow of the American Heart Association

2017 The American Physiological Society (APS) Cardiovascular Section New Investigator Award

Current Guest Research Topic in Frontiers in Physiology:

Neuropeptides as Central Mediators of Cardiovascular Disease

https://www.frontiersin.org/research-topics/6918/neuropeptides-as-central-mediators-of-cardiovascular-disease

Selected Publications:

1.Widiapradja A, Chunduri P, Levick SP. The role of neuropeptides in adverse myocardial remodeling andheart failure. Cell and Molecular Life Sciences, 2017;74:2019-2038.

2. Jubair S, Li J, Dehlin HM, Manteufel EJ, Levick SP, Janicki JS. Substance P induces cardioprotection from

ischemia via activation of AKT. Am J Physiol: Heart Circ Physiol , 2015;309:H676-H684.

3. Melendez GC, Manteufel EJ, Dehlin HM, Register TC, Levick SP. Non-human primate and rat cardiac

fibroblasts show similar extracellular matrix-related and cellular adhesion gene responses to substance P. Heart,

Lung, and Circulation , 2015;24:395-403.

4. Dehlin HM, Manteufel EJ, Monroe AL, Reimer MH, Levick SP. Substance P acting via the neurokinin-1

receptor regulates adverse myocardial remodeling in a rat model of hypertension. Int J Cardiol , 2013;168:4643-

4651.

5. Melendez GC, Li J, Law BA, Janicki JS, Supowit SC, Levick SP. Substance P Induces Adverse Myocardial

Remodeling via a Mechanism Involving Cardiac Mast Cells. Cardiovascular Research , 2011;92:420-9.

6. McLarty JL, Melendez GC, Brower GL, Janicki JS, Levick SP. Tryptase/Protease-activated receptor 2

interactions induce selective mitogen-activated protein kinase signaling and collagen synthesis by cardiac

fibroblasts. Hypertension . 2011;58:264-70.

7. Levick SP, McLarty JL, Murray DB, Freeman RM, Carver WE, Brower GL. Cardiac mast cells mediate left

ventricular fibrosis in the hypertensive rat heart. Hypertension . 2009;53:1041-7.

International links

China

(Second Affiliated Hospital of Nanjing Medical University) In this collaboration with Dr. Chen Qu we are investigating the role of substance P in myocardial infarction.

Czech Republic

(Czech Academy of Sciences) In this collaboration with Dr. Jan Neckar, PhD we are determining the role of the neuropeptide substance P as a molecular switch that determines whether physiological or pathological hypertrophy develops in response to heamodynamic load on the heart.

United States

(Wake Forest University School of Medicine) In this collaboration with Dr. Giselle Melendez, MD we are determining the role of the neurokinin-1 receptor in doxorubicin-induced cardiotoxicity.

Selected grants

2017

  • Cardiovascular Diseases Research; Levick S; National Institutes of Health (USA)/Research Grant.
  • George and Mary Thompson Fellowship; Levick S; Northern Sydney Local Health District/George and Mary Thompson Fellowship.

Selected publications

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Book Chapters

  • Janicki, J., Brower, G., Levick, S. (2014). The emerging prominence of the cardiac mast cell as a potent mediator of adverse myocardial remodeling. In M R Hughes, K M McNagny (Eds.), Mast Cells: Methods and Protocols, (pp. 121-139). New York: Springer. [More Information]

Journals

  • Levick, S., Widiapradja, A. (2018). Mast cells: Key contributors to cardiac fibrosis. International Journal of Molecular Sciences, 19(1). [More Information]
  • Levick, S. (2018). Substance P and the neurokinin-1 receptor in the ischaemic heart: Two sides to the coin. International Journal of Cardiology, 271, 258-259. [More Information]
  • Widiapradja, A., Chunduri, P., Levick, S. (2017). The role of neuropeptides in adverse myocardial remodeling and heart failure. Cellular and Molecular Life Sciences, 74(11), 2019-2038. [More Information]
  • Sharma, A., Khan, M., Levick, S., Lee, K., Hammock, B., Imig, J. (2016). Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis. International Journal of Molecular Sciences, 17(5), 1-11. [More Information]
  • Li, J., Jubair, S., Levick, S., Janicki, J. (2016). The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis. IJC Metabolic & Endocrine, 10, 16-23. [More Information]
  • Bower, G., Levick, S., Janicki, J. (2015). Differential Effects of Prevention and Reversal Treatment with Lisinopril on Left Ventricular Remodelling in a Rat Model of Heart Failure. Heart, Lung and Circulation, 24(9), 919-924. [More Information]
  • Melendez, G., Manteufel, E., Dehlin, H., Register, T., Levick, S. (2015). Non-human Primate and Rat Cardiac Fibroblasts Show Similar Extracellular Matrix-related and Cellular Adhesion Gene Responses to Substance P. Heart, Lung and Circulation, 24(4), 395-403. [More Information]
  • Jubair, S., Li, J., Dehlin, H., Manteufel, E., Goldspink, P., Levick, S., Janicki, J. (2015). Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT. American Journal of Physiology - Heart and Circulatory Physiology, 309(4), H676-H684. [More Information]
  • Janicki, J., Brower, G., Levick, S. (2015). The emerging prominence of the cardiac mast cell as a potent mediator of adverse myocardial remodeling. Methods in Molecular Biology, 1220, 121-139. [More Information]
  • Levick, S., Goldspink, P. (2014). Could interferon-gamma be a therapeutic Target for treating heart failure? Heart Failure Reviews, 19(2), 227-236. [More Information]
  • Dehlin, H., Levick, S. (2014). Substance P in heart failure: The good and the bad. International Journal of Cardiology, 170(3), 270-277. [More Information]
  • Li, J., Levick, S., DiPette, D., Janicki, J., Supowit, S. (2013). Alpha-calcitonin gene-related peptide is protective against pressure overload-induced heart failure. Regulatory Peptides, 185, 20-28. [More Information]
  • McLarty, J., Li, J., Levick, S., Janicki, J. (2013). Estrogen modulates the influence of cardiac inflammatory cells on function of cardiac fibroblasts. Journal of Inflammation Research, 6(1), 99-108. [More Information]
  • Janicki, J., Spinale, F., Levick, S. (2013). Gender differences in non-ischemic myocardial remodeling: Are they due to estrogen modulation of cardiac mast cells and/or membrane type 1 matrix metalloproteinase. Pfluegers Archiv: European journal of physiology, 465(5), 687-697. [More Information]
  • Dehlin, H., Manteufel, E., Monroe, A., Reimer Jr., M., Levick, S. (2013). Substance P acting via the neurokinin-1 receptor regulates adverse myocardial remodeling in a rat model of hypertension. International Journal of Cardiology, 168(5), 4643-4651. [More Information]
  • Law, B., Levick, S., Carver, W. (2012). Alterations in Cardiac Structure and Function in a Murine Model of Chronic Alcohol Consumption. Microscopy and Microanalysis, 18(3), 453-461. [More Information]
  • McLarty, J., Melendez, G., Levick, S., Bennett, S., Sabo-Attwood, T., Brower, G., Janicki, J. (2012). Estrogenic modulation of inflammation-related genes in male rats following volume overload. Physiological Genomics, 44(6), 362-373. [More Information]
  • Lu, H., Melendez, G., Levick, S., Janicki, J. (2012). Prevention of adverse cardiac remodeling to volume overload in female rats is the result of an estrogen-altered mast cell phenotype. American Journal of Physiology - Heart and Circulatory Physiology, 302(3), H811-H817. [More Information]
  • Li, J., Lu, H., Plante, E., Melendez, G., Levick, S., Janicki, J. (2012). Stem cell factor is responsible for the rapid response in mature mast cell density in the acutely stressed heart. Journal of Molecular and Cellular Cardiology, 53(4), 469-474. [More Information]
  • Levick, S., Melendez, G., Plante, E., McLarty, J., Brower, G., Janicki, J. (2011). Cardiac mast cells: The centrepiece in adverse myocardial remodelling. Cardiovascular Research, 89(1), 12-19. [More Information]
  • Chan, V., Fenning, A., Levick, S., Loch, D., Chunduri, P., Iyer, A., Teo, Y., Hoey, A., Wilson, K., et al (2011). Cardiovascular Changes During Maturation and Ageing in Male and Female Spontaneously Hypertensive Rats. Journal of Cardiovascular Pharmacology, 57(4), 469-478. [More Information]
  • McLarty, J., Melendez, G., Spencer, W., Levick, S., Brower, G., Janicki, J. (2011). Isolation of functional cardiac immune cells. Journal of Visualized Experiments, 58(58), 1-5. [More Information]
  • Melendez, G., Li, J., Law, B., Janicki, J., Supowit, S., Levick, S. (2011). Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells. Cardiovascular Research, 92(3), 420-429. [More Information]
  • McLarty, J., Melendez, G., Brower, G., Janicki, J., Levick, S. (2011). Tryptase/protease-activated receptor 2 interactions induce selective mitogen-activated protein kinase signaling and collagen synthesis by cardiac fibroblasts. Hypertension, 58(2), 264-270. [More Information]

2018

  • Levick, S., Widiapradja, A. (2018). Mast cells: Key contributors to cardiac fibrosis. International Journal of Molecular Sciences, 19(1). [More Information]
  • Levick, S. (2018). Substance P and the neurokinin-1 receptor in the ischaemic heart: Two sides to the coin. International Journal of Cardiology, 271, 258-259. [More Information]

2017

  • Widiapradja, A., Chunduri, P., Levick, S. (2017). The role of neuropeptides in adverse myocardial remodeling and heart failure. Cellular and Molecular Life Sciences, 74(11), 2019-2038. [More Information]

2016

  • Sharma, A., Khan, M., Levick, S., Lee, K., Hammock, B., Imig, J. (2016). Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis. International Journal of Molecular Sciences, 17(5), 1-11. [More Information]
  • Li, J., Jubair, S., Levick, S., Janicki, J. (2016). The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis. IJC Metabolic & Endocrine, 10, 16-23. [More Information]

2015

  • Bower, G., Levick, S., Janicki, J. (2015). Differential Effects of Prevention and Reversal Treatment with Lisinopril on Left Ventricular Remodelling in a Rat Model of Heart Failure. Heart, Lung and Circulation, 24(9), 919-924. [More Information]
  • Melendez, G., Manteufel, E., Dehlin, H., Register, T., Levick, S. (2015). Non-human Primate and Rat Cardiac Fibroblasts Show Similar Extracellular Matrix-related and Cellular Adhesion Gene Responses to Substance P. Heart, Lung and Circulation, 24(4), 395-403. [More Information]
  • Jubair, S., Li, J., Dehlin, H., Manteufel, E., Goldspink, P., Levick, S., Janicki, J. (2015). Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT. American Journal of Physiology - Heart and Circulatory Physiology, 309(4), H676-H684. [More Information]
  • Janicki, J., Brower, G., Levick, S. (2015). The emerging prominence of the cardiac mast cell as a potent mediator of adverse myocardial remodeling. Methods in Molecular Biology, 1220, 121-139. [More Information]

2014

  • Levick, S., Goldspink, P. (2014). Could interferon-gamma be a therapeutic Target for treating heart failure? Heart Failure Reviews, 19(2), 227-236. [More Information]
  • Dehlin, H., Levick, S. (2014). Substance P in heart failure: The good and the bad. International Journal of Cardiology, 170(3), 270-277. [More Information]
  • Janicki, J., Brower, G., Levick, S. (2014). The emerging prominence of the cardiac mast cell as a potent mediator of adverse myocardial remodeling. In M R Hughes, K M McNagny (Eds.), Mast Cells: Methods and Protocols, (pp. 121-139). New York: Springer. [More Information]

2013

  • Li, J., Levick, S., DiPette, D., Janicki, J., Supowit, S. (2013). Alpha-calcitonin gene-related peptide is protective against pressure overload-induced heart failure. Regulatory Peptides, 185, 20-28. [More Information]
  • McLarty, J., Li, J., Levick, S., Janicki, J. (2013). Estrogen modulates the influence of cardiac inflammatory cells on function of cardiac fibroblasts. Journal of Inflammation Research, 6(1), 99-108. [More Information]
  • Janicki, J., Spinale, F., Levick, S. (2013). Gender differences in non-ischemic myocardial remodeling: Are they due to estrogen modulation of cardiac mast cells and/or membrane type 1 matrix metalloproteinase. Pfluegers Archiv: European journal of physiology, 465(5), 687-697. [More Information]
  • Dehlin, H., Manteufel, E., Monroe, A., Reimer Jr., M., Levick, S. (2013). Substance P acting via the neurokinin-1 receptor regulates adverse myocardial remodeling in a rat model of hypertension. International Journal of Cardiology, 168(5), 4643-4651. [More Information]

2012

  • Law, B., Levick, S., Carver, W. (2012). Alterations in Cardiac Structure and Function in a Murine Model of Chronic Alcohol Consumption. Microscopy and Microanalysis, 18(3), 453-461. [More Information]
  • McLarty, J., Melendez, G., Levick, S., Bennett, S., Sabo-Attwood, T., Brower, G., Janicki, J. (2012). Estrogenic modulation of inflammation-related genes in male rats following volume overload. Physiological Genomics, 44(6), 362-373. [More Information]
  • Lu, H., Melendez, G., Levick, S., Janicki, J. (2012). Prevention of adverse cardiac remodeling to volume overload in female rats is the result of an estrogen-altered mast cell phenotype. American Journal of Physiology - Heart and Circulatory Physiology, 302(3), H811-H817. [More Information]
  • Li, J., Lu, H., Plante, E., Melendez, G., Levick, S., Janicki, J. (2012). Stem cell factor is responsible for the rapid response in mature mast cell density in the acutely stressed heart. Journal of Molecular and Cellular Cardiology, 53(4), 469-474. [More Information]

2011

  • Levick, S., Melendez, G., Plante, E., McLarty, J., Brower, G., Janicki, J. (2011). Cardiac mast cells: The centrepiece in adverse myocardial remodelling. Cardiovascular Research, 89(1), 12-19. [More Information]
  • Chan, V., Fenning, A., Levick, S., Loch, D., Chunduri, P., Iyer, A., Teo, Y., Hoey, A., Wilson, K., et al (2011). Cardiovascular Changes During Maturation and Ageing in Male and Female Spontaneously Hypertensive Rats. Journal of Cardiovascular Pharmacology, 57(4), 469-478. [More Information]
  • McLarty, J., Melendez, G., Spencer, W., Levick, S., Brower, G., Janicki, J. (2011). Isolation of functional cardiac immune cells. Journal of Visualized Experiments, 58(58), 1-5. [More Information]
  • Melendez, G., Li, J., Law, B., Janicki, J., Supowit, S., Levick, S. (2011). Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells. Cardiovascular Research, 92(3), 420-429. [More Information]
  • McLarty, J., Melendez, G., Brower, G., Janicki, J., Levick, S. (2011). Tryptase/protease-activated receptor 2 interactions induce selective mitogen-activated protein kinase signaling and collagen synthesis by cardiac fibroblasts. Hypertension, 58(2), 264-270. [More Information]

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