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Dr Chrishan Samuel
Current Position
Senior Research Fellow
Address
Department of Pharmacology Monash University Clayton, Victoria, 3800 Australia
Email: chrishan.samuel@monash.edu Phone: +61 3 9902 0152 Facsimile: +61 3 9902 9500
Chrishan Samuel received his PhD from the Howard Florey Institute, University of Melbourne in 1999, working with Professors John Coghlan and John Bateman to determine the extracellular matrix remodelling actions of the hormone, relaxin, specifically in relation to its ability to soften the pelvic ligaments of pregnant mammals, which is required for successful parturition. He then completed 2 years of postdoctoral training in the Department of Dermatology, Stanford University and Molecular Medicine Research Institute (California, USA), where he further studied matrix proteins (collagens, fibrillins) that served as targets of relaxin activity.
Chrishan returned to Australia in early 2001 and re-joined the Relaxin Team at the Howard Florey Institute, establishing the Relaxin-Fibrosis Laboratory in 2002, which focused on developing novel therapeutic strategies for cardiac and renal fibrosis (scar tissue accumulation), a hallmark of most forms of heart and kidney disease; with particular attention to defining the anti-fibrotic potential of relaxin and related peptides. During this time, he produced over 70 publications and his research was supported by an ARC Postdoctoral Fellowship (2002-2004); an NHFA/NHMRC RD Wright Career Development Fellowship (2007-2011); and various grants from the NHMRC, ARC, NHF, ASCC as well as various commercial sources. In September 2011, he was recruited to the Department of Pharmacology at Monash University, where he heads the Fibrosis Laboratory.
Chrishan's work has shown that relaxin protects the ageing and injured heart and kidney from fibrosis progression, and is a rapidly-acting but safe anti-fibrotic that prevents and/or reverses scar tissue build-up in various diseases (fibrotic cardiomyopathy, hypertension, myocardial infarction, diabetic cardiomyopathy, tubulointerstitial renal fibrosis), regardless of etiology. His current work involves identifying novel therapeutic targets for fibrosis regression/cardioprotection by relaxin; comparing its rapid-occurring efficacy to existing therapeutics for heart/kidney disease; and determining if relaxin can facilitate existing/other novel therapies/other hormones to maximise their therapeutic potential. He also continues to collaborate with others to further develop other novel treatment options as anti-fibrotics.
Collaborators
- A/Professor Ross Bathgate (Florey Neuroscience Institutes, Melbourne)
- A/Professor Xiao-Jun Du (Baker IDI Heart and Diabetes Institute, Melbourne)
- A/Professor Tim Hewitson (Dept. of Nephrology, Royal Melbourne Hospital, Melbourne)
- A/Professor Darren Kelly (Dept. of Medicine, St. Vincent's Hospital, Melbourne)
- Professor Karl Kunzelmann (University of Regensburg, Germany)
- Dr Michael Mathai (School of Biomedical and Health Sciences, Victoria University)
- A/Professor Yuben Moodley (Dept. of Respiratory Medicine, University of Western Australia, WA)
- Professor Nadia Rosenthal (Australian Regenerative Medicine Institute, Melbourne)
- A/Professor Sharon Ricardo (Monash Immunology and Stem Cell Laboratories, Melbourne)
- Professor Prashanthan Sanders (Cardiovascular Research Centre, University of Adelaide, SA)
- Dr Dennis Stewart and Dr Elaine Unemori (Corthera Inc., San Mateo, CA, USA)
- Professor Roger Summers (Dept. of Pharmacology, Monash University)
- A/Professor Mimi Tang (Dept. of Allergy and Immunology, Royal Children's Hospital)
- Professor John Wade (Florey Neuroscience Institutes, Melbourne)
- A/Professor Yong Zhou (University of Alabama, USA)
Publications (2005-present)
- Alikhan MA, Jones CV, Williams TM, Beckhouse AG, Kett MK, Fletcher AL, Sakkal S, Samuel CS, Ramsay RG, Deane JA, Wells CA, Little MH, Hume DA, Ricardo SD (2011) Colony-stimulating factor (CSF)-1 promotes kidney growth and repair via alteration of a macrophage response. Am J Path 179(3):1243-1256. PMID: 21762674
- Hossain MA, Chow BSM, Zhao C, Xu Q, Du XJ, Wade JD, Samuel CS (2011) H3 relaxin demonstrates anti-fibrotic properties via the RXFP1 receptor. Biochemistry 50(8):1368-1375. PMID: 21229994
- Samuel CS, Cendrawan S, Gao XM, Ming Z, Zhao C, Kiriazis H, Xu Q, Tregear GW, Bathgate RAD, Du XJ (2011) Relaxin remodels fibrotic healing following myocardial infarction. Lab Invest 91(5):675-690 PMID: 21221074
- Chan LJ, Hossain MA, Samuel CS, Separovic F, Wade JD (2011) The Relaxin Peptide Family – Structure, Function and Clinical Applications. Prot Pept Lett 18(3):220-229. PMID: 20858209
- Pini A, Shemesh R, Samuel CS, Bathgate RAD, Zauberman A, Hermesh C, Wool A, Bani D, Rotman G (2010) Prevention of bleomycin induced pulmonary fibrosis by a novel anti-fibrotic peptide with relaxin like activity. J Pharm Exp Therap 335(3):589-599. PMID: 20826567
- Hewitson TD, Ho WY, Samuel CS (2010) Anti-fibrotic properties of relaxin - in vivo mechanism of action in experimental renal tubulointerstitial fibrosis. Endocrinology 151(10):4938-4948. PMID: 20826562
- Moodley Y, Ilancheran S, Samuel C, Vaghjiani V, Atienza D, Williams ED, Jenkin G, Wallace E, Trounson A, Manuelpillai U (2010) Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair. Am J Respir Crit Care Med 182(5):643-651. PMID: 20522792
- Manuelpillai U, Tchongue T, Lourensz D, Vaghijani V, Samuel CS, Liu A, Williams ED, Sievert W (2010) Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4 treated mice. Cell Transplant 19(9):1157-1168. PMID: 20447339
- Hossain MA, Samuel CS, Binder C, Hewitson TD, Tregear GW, Wade JD, Bathgate RAD (2010) The chemically synthesized human relaxin-2 analog, B-R13/17K H2, is an RXFP1 antagonist. Amino Acids 39(2):409-416. PMID: 20043231
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Wong SE, Winbanks CE, Samuel CS, Hewitson TD (2010) Lectin histochemistry for light and electron microscopy. Methods Mol Biol 611:103-114. PMID: 19960325
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Du XJ, Bathgate RA, Samuel CS, Dart AM, Summers RJ (2010) Cardiovascular effects of relaxin: from basic science to clinical therapy. Nat Rev Cardiol 7(1):48-58. PMID: 19935741
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Giannakis E, Samuel CS, Hewitson TD, Boon WM, Macris M, Reeve S, Lawrence J, Smith AI, Tregear GW, Wade JD (2009) Aberrant protein expression in plasma and kidney tissue during experimental obstructive nephropathy. Proteomics Clin Applic 3(10):1211-1224. PMID: 21136945
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Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounsan A (2009) Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Path 175 (1):303-313. PMID: 19497992
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Tang ML, Samuel CS, Royce SG (2009) Role of relaxin in regulation of fibrosis in the lung. Ann N Y Acad Sci 1160:342-347. PMID: 19416216
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Samuel CS, Mookerjee I, Halls ML, Summers RJ, Chew E, Bathgate RA, Tregear GW, Hewitson TD (2009) Investigations into the inhibitory effects of relaxin on renal myofibroblast differentiation. Ann N Y Acad Sci 1160:294-299. PMID: 19416207
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Hewitson TD, Samuel CS (2009) Relaxin: an endogenous renoprotective factor? Ann N Y Acad Sci 1160:289-293. PMID: 19416206
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Du XJ, Xu Q, Lekgabe E, Gao XM, Kiriazis H, Moore XL, Dart AM, Tregear GW, Bathgate RA, Samuel CS (2009) Reversal of cardiac fibrosis and related dysfunction by relaxin. Ann N Y Acad Sci 1160:278-284. PMID: 19416203
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Tregear GW, Bathgate RA, Hossain MA, Lin F, Zhang S, Shabanpoor F, Scott DJ, Ma S, Gundlach AL, Samuel CS, Wade JD (2009) Structure and activity in the relaxin family of peptides. Ann N Y Acad Sci 1160:5-10. PMID: 19416150
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Royce SG, Miao YR, Lee M, Samuel CS, Tregear GW, Tang MLK (2009) Relaxin reverses airway remodeling and airway dysfunction in allergic airways disease. Endocrinology 150(6):2692-2699. PMID: 19213838
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Samuel CS (2009) Determination of collagen content, concentration, and sub-types in kidney tissue. Methods Mol Biol 2009;466:223-235. PMID: 19148607
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Giannakis E, Samuel CS, Boon WM, Macris M, Hewitson TD, Wade JD (2009 SELDI-TOF mass spectrometry-based protein profiling of kidney tissue. Methods Mol Biol 466:237-249. PMID: 19148606
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Samuel CS, Hewitson TD (2009) Relaxin and the progression of kidney disease. Curr Opin Nephrol Hypertens 18(1):9-14. PMID: 19077683
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Mookerjee I, Hewitson TD, Halls ML, Summers RJ, Mathai ML, Bathgate RA, Tregear GW, Samuel CS (2009) Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and Smad2. FASEB J 23(4):1219-1229. PMID: 19073841
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Samuel CS, Royce SG, Chen B, Cao H, Gossen JA, Tregear GW, Tang ML (2009) Relaxin family peptide receptor-1 protects against airway fibrosis during homeostasis but not against fibrosis associated with chronic allergic airways disease. Endocrinology 150(3):1495-1502. PMID: 18974264
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van der Westhuizen ET, Halls ML, Samuel CS, Bathgate RA, Unemori EN, Sutton SW, Summers RJ (2008) Relaxin family peptide receptors--from orphans to therapeutic targets. Drug Discov Today 13(15-16):640-651. PMID: 18675759
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Samuel CS, Hewitson TD, Zhang Y, Kelly DJ (2008) Relaxin ameliorates fibrosis in experimental diabetic cardiomyopathy. Endocrinology 149(7):3286-3293. PMID: 18388190
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Fang L, Gao XM, Samuel CS, Su Y, Lim YL, Dart AM, Du XJ (2008) Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction. Clin Sci (Lond) 115(3):99-106. PMID: 18248324
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Xu Q, Lekgabe ED, Gao XM, Ming Z, Tregear GW, Dart AM, Bathgate RA, Samuel CS, Du XJ (2008) Endogenous relaxin does not affect chronic pressure overload-induced cardiac hypertrophy and fibrosis. Endocrinology 149(2):476-482. PMID: 17991721
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Bathgate RA, Lekgabe ED, McGuane JT, Su Y, Pham T, Ferraro T, Layfield S, Hannan RD, Thomas WG, Samuel CS, Du XJ (2008) Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis. Mol Cell Endocrinol 280(1-2):30-38. PMID: 17961912
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Samuel CS, Lekgabe ED, Mookerjee I (2007) The effects of relaxin on extracellular matrix remodeling in health and fibrotic disease. Adv Exp Med Biol 2007;612:88-103. PMID: 18161483
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Samuel CS, Royce SG, Burton MD, Zhao C, Tregear GW, Tang ML (2007) Relaxin plays an important role in the regulation of airway structure and function. Endocrinology 148(9):4259-4266. PMID: 17584966
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Samuel CS, Hewitson TD, Unemori EN, Tang ML (2007) Drugs of the future: the hormone relaxin. Cell Mol Life Sci 64(12):1539-1557. PMID: 17458501
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Samuel CS, Lin F, Hossain MA, Zhao C, Ferraro T, Bathgate RA, Tregear GW, Wade JD (2007) Improved chemical synthesis and demonstration of the relaxin receptor binding affinity and biological activity of mouse relaxin. Biochemistry 46(18):5374-5381. PMID: 17425335
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Locke NR, Royce SG, Wainewright JS, Samuel CS, Tang ML (2007) Comparison of airway remodeling in acute, subacute, and chronic models of allergic airways disease. Am J Respir Cell Mol Biol 36(5):625-632. PMID: 17237192
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Hewitson TD, Mookerjee I, Masterson R, Zhao C, Tregear GW, Becker GJ, Samuel CS (2007) Endogenous relaxin is a naturally occurring modulator of experimental renal tubulointerstitial fibrosis. Endocrinology 148(2):660-669. PMID: 17095590
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Kistler PM, Sanders P, Dodic M, Spence SJ, Samuel CS, Zhao C, Charles JA, Edwards GA, Kalman JM (2006) Atrial electrical and structural abnormalities in an ovine model of chronic blood pressure elevation after prenatal corticosteroid exposure: implications for development of atrial fibrillation. Eur Heart J 27(24):3045-3056. PMID: 17098760
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Lekgabe ED, Royce SG, Hewitson TD, Tang ML, Zhao C, Moore XL, Tregear GW, Bathgate RA, Du XJ, Samuel CS (2006) The effects of relaxin and estrogen deficiency on collagen deposition and hypertrophy of nonreproductive organs. Endocrinology 147(12):5575-5583. PMID: 16935837
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Samuel CS, Du XJ, Bathgate RA, Summers RJ (2006) 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin in the treatment of cardiovascular disease. Pharmacol Therap 112(2):529-552. PMID: 16814863
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Samuel CS, Hewitson TD (2006) Relaxin in cardiovascular and renal disease. Kidney Int 69(9):1498-1502. PMID: 16672919
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Fu P, Shen PJ, Zhao CX, Scott DJ, Samuel CS, Wade JD, Tregear GW, Bathgate RA, Gundlach AL (2006) Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by insulin-like peptide-3 of glomerular cell proliferation. J Endocrinol 189(2):397-408. PMID: 16648305
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Bathgate RA, Lin F, Hanson NF, Otvos L Jr, Guidolin A, Giannakis C, Bastiras S, Layfield SL, Ferraro T, Ma S, Zhao C, Gundlach AL, Samuel CS, Tregear GW, Wade JD (2006) Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo. Biochemistry 45(3):1043-1053. PMID: 16411781
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Mookerjee I, Solly NR, Royce SG, Tregear GW, Samuel CS, Tang ML (2006) Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease. Endocrinology 147(2):754-761. PMID: 16254028
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Samuel CS (2005) Relaxin: antifibrotic properties and effects in models of disease. Clin Med Res. 3(4):241-249. PMID: 16303890
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Cochrane AL, Kett MM, Samuel CS, Campanale NV, Anderson WP, Hume DA, Little MH, Bertram JF, Ricardo SD (2005) Renal structural and functional repair in a mouse model of reversal of ureteral obstruction. J Am Soc Nephrol 16(12):3623-3630. PMID: 16221872
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Samuel CS, Zhao C, Yang Q, Wang H, Tian H, Tregear GW, Amento EP (2005) The relaxin gene knockout mouse: a model of progressive scleroderma. J Invest Dermatol 125(4):692-699. PMID: 16185267
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Lekgabe ED, Kiriazis H, Zhao C, Xu Q, Moore XL, Su Y, Bathgate RA, Du XJ, Samuel CS (2005) Relaxin reverses cardiac and renal fibrosis in spontaneously hypertensive rats. Hypertension 46(2):412-418. PMID: 15967869
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Mookerjee I, Tang ML, Solly N, Tregear GW, Samuel CS (2005) Investigating the role of relaxin in the regulation of airway fibrosis in animal models of acute and chronic allergic airway disease. Ann N Y Acad Sci 1041:194-196. PMID: 15956707
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Mookerjee I, Unemori EN, DU XJ, Tregear GW, Samuel CS (2005) Relaxin modulates fibroblast function, collagen production, and matrix metalloproteinase-2 expression by cardiac fibroblasts. Ann N Y Acad Sci 1041:190-193. PMID: 15956706
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Samuel CS, Mookerjee I, Masterson R, Tregear GW, Hewitson TD (2005) Relaxin regulates collagen overproduction associated with experimental progressive renal fibrosis. Ann N Y Acad Sci 1041:182-184. PMID: 15956704
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Samuel CS, Zhao C, Bathgate RA, DU XJ, Summers RJ, Amento EP, Walker LL, McBurnie M, Zhao L, Tregear GW (2005) The relaxin gene-knockout mouse: a model of progressive fibrosis. Ann N Y Acad Sci 1041:173-181. PMID: 15956703
- Tozzi CA, Poiani GJ, McHugh NA, Shakarjian MP, Grove BH, Samuel CS, Unemori EN, Riley DJ (2005) Recombinant human relaxin reduces hypoxic pulmonary hypertension in the rat. Pulm Pharmacol Therap 18(5):346-353. PMID: 15939313
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