Professor Shane T. Grey | UNSW Research

Keywords

Biography

Dr Shane T. Grey received his PhD training in immunology at Monash University (1996) and his post-doctoral training (1996-1998) at Harvard Medical School, USA, where he moved through the ranks first as an Instructor in Surgery (1998) then Assistant Professor (2001). He was then recruited to the Garvan Institute where he has led a biomedical research team since 2004. Shane’s key research interests lie in the genetic control of inflammation, particularly how the TNFAIP3 gene and NF-kB-system interact to impact tissue and immune cell inflammation, immunological tolerance and human disease. Shane’s fundamental research is highly influential, with over 100 career publications garnering ~3,200 new cites since 2017 (~9,700 total), giving him a FWCI of 2.38 and an h-index of 53 (Google Scholar). In the last few years, he has been particularly productive, publishing papers in leading journals (e.g. Nature Immunol; Nature Comms; J Exp Med; Cell Reports; Diabetes; J. Immunol.). Shane is very keen to translate fundamental findings to clinical impact including as a lead investigator on Australia's first clinical islet transplant program; and leadership of a first in human safety study testing a novel anti-inflammatory gene therapy in transplantation developed in his lab. Shane has been recognised for his diabetes and transplantation contributions with an NSW BioFirst Award (2003); an ARC Future Fellowship (2009); Key Opinion Leader (KOL) in transplantation by The Transplantation Society International (2007); a JDRF-Macquarie Group Foundation Innovation Award (2010); and a TSANZ “Ian McKenzie Prize” – for outstanding contributions in Transplantation (2012) and NHMRC Fellowships (2013; 2018). Shane is sought after as a reviewer for manuscripts and grants as well as a commercial consultant nationally and internationally. Through the development of his research program Shane has led and worked within multi-disciplinary teams that include clinical and basic researchers, across diverse ARC- and NHMRC-funded programs, and with interactions with multiple international and national institutions including MRIs, Universities, Hospitals and Biotech. Shane is committed to the development of inclusive and safe working environments as evidenced by past involvement in the Franklin Women Mentoring program, as well as Shane’s role spearheading institutional policy and practice as Chair of the Good Working Behaviours as well as Engagement Committees at the Garvan Institute. This demonstrated commitment to the principles of diversity, equity and inclusion would contribute to the advancement of BABS as a dynamic, equitable and safe working environment.

My Qualifications

B.Sc. (Physiology/Genetics) La Trobe University, Melbourne 1984
B.Sc. Honours (Immunology) Monash University, Melbourne 1988
Ph.D (Immunology) Monash University, Melbourne 1991-1996
Postdoctoral Studies (Transplant Immunology) Harvard Medical School, Boston 1996-1998
Instructor in Surgery, Harvard Medical School, Boston 1998-2000
Assistant Professor in Surgery, Harvard Medical School, Boston 2001-2004

My Awards

2000 JDRF International Career Development Award

2001 Assistant Professor in Surgery, Harvard Medical School.

2004 NSW-BioFirst Award

2004 Senior Research Fellow, Garvan Medical Research Institute, Sydney, Australia.

2005 Mary Jane Kugel Award, JDRF New York

2007 “Key Opinion Leader (KOL)” award in transplantation – TTS

2008 Mary Jane Kugel Award, JDRF New York

2009 Australian Research Council (ARC) Future Fellow Award

2009 NHMRC Senior Research Fellowship SRF A

2010 JDRF and Macquarie Group Foundation Diabetes Research Innovation Award

2011 Associate Professor, Faculty of Medicine, UNSW, Sydney, Australia

2012 TSANZ “Ian McKenzie Prize” – for outstanding contributions in Transplantation

2018 NHMRC Senior Research Fellowship SRF B

My Research Activities

1 - Grey has made important contributions to our understanding of TNFAIP3’s function in inflammation (~22 publications & x3 PhD thesis focused on A20 biology), having being the first to identify A20/TNFAIP3 as an tissue [islet] expressed gene (Grey, JEM 1999) and more recently showing how A20 variants tune inflammation (Grey last author Nat. Immunol 2019). The latter study was highlighted in commentaries in both Nature Immunology and Nature Reviews Immunology. Further studies highlight how A20 contributes to Mendelian disease in patients treated at UNSW has been reviewed with positive comments and invited resubmission (J. Clinical Investigation Citescore: 17).

a. Nathan W. Zammit, Owen M. Siggs, Paul Gray, Keisuke Horikawa et., al Shane T. Grey. Denisovan, modern human, and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity. Nature Immunology Sept 2019.

**Cover article and released with a commentary & Altmetric score 200+.

b. Zammit NW, Walters SN, Seeberger KL, O'Connell PJ, Korbutt GS, Grey ST. A20 as an immune tolerance factor can determine islet transplant outcomes.

JCI Insight. 2019 Nov 1;4(21):e131028.

c. D Liuwantara, M Elliot, MW Smith, AO Yam, ... Grey, ST. Nuclear Factor κB Regulates β Cell Death A Critical Role for A20 in β Cell Protection. Diabetes 2006, 55 (9), 249173;2501. PMID: 16936197

d. Daniel S, Arvelo MB, Patel VI, Longo CR, Shrikhande G, Shukri T, Mahiou J, Sun DW, Mottley C, Grey ST, Ferran C. A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation. Blood. 2004 Oct 15;104(8):2376-84. PMID:15251990

e. Grey ST*, Longo C, Shukri T, Patel VI, Csizmadia E, Daniel S, Arvelo MB, Tchipashvili V, Ferran C*.

Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. J Immunol. 2003 Jun 15;170(12):6250-6. PMID:12794157. *Grey is equal senior & co-corresponding author.

f. Shane T. Grey*, Maria B. Arvelo, Wendy Hasenkamp, Fritz H. Bach, Christiane Ferran*. A20 Inhibits Cytokine-Induced Apoptosis and NF-kB Dependent Gene Activation in Islets. J. Exp. Med., 1999, 190 (8), 1135-1145. PMID:10523611. *Grey is equal senior & co-corresponding author.

2 - Further, A20 regulates the NF-kB system and Grey has identified key functional components of the NF-kB system in pancreatic islets including BIRC 2&3, TRAF2&3, NIK; as well as A20.

a. Zammit NW, Grey ST. Equipping the islet graft for self defence: targeting nuclear factor κB and implications for tolerance. Curr Opin Organ Transplant. 2018 Feb;23(1):97-105. PMID:29120883

b. Malle EK, Zammit NW, Walters SN, Koay YC, Wu J, Tan BM, Villanueva JE, Brink R, Loudovaris T, Cantley J, McAlpine SR, Hesselson D, Grey ST. Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity. J Exp Med. 2015 Jun 29. PMID:26122662.

*Released with commentary.

c. B. M. Tan, N. W. Zammit, A. O. Yam, R. Slattery, S. N. Walters, E. Malle and S. T. Grey. BIRC proteins fine-tune TNF-induced NF-kB and JNK signalling in pancreatic beta cells. Diabetologia. 2013 Mar;56(3):520-32. PMID: 23250032

d. Zammit NW, Tan BM, Walters SN, Liuwantara D, Villanueva JE, Malle EK, Grey ST. Low-dose rapamycin unmasks the protective potential of targeting intragraft NF-κB for islet transplants. Cell Transplant. 2013;22(12):2355-66. PMID:23127588

e. Zammit NW, Wong YY, Walters SN, Warren J, Barry SC, Grey ST. RELA governs a network of islet-specific metabolic genes necessary for beta cell function. Diabetologia. 2023 Aug;66(8):1516-1531. PMID: 37311878

3 - Grey has made important contributions to clinical translation of islet transplantation, through the development of novel islet trophic factors with translational potential, and significantly, as a lead co-PI on Australia’s first clinical islet transplant trial. This trial changed Australian medical practice with the Federal adoption (reimbursed through NFC scheme) of islet transplantation as a treatment for some T1D patients and resulted in a number of clinical/translational research papers highlighted below. In further translation, this application seeks support to develop A20 as an anti-inflammatory agent for use in islet transplantation. Excitingly, this work is advancing with the RAH being the intended performance site for this first in human study – in collaboration with Professor Toby Coates. Grey’s experience in clinical translation and understanding in speaking the languages of basic and clinical science strongly supports his translational capabilities.

a. Loh K,Shi YC, Walters S, Bensellam M, Lee K, Dezaki K, Nakata M, Ip CK, Chan JY, Gurzov EN, Thomas HE, Waibel M, Cantley J, Kay TW, Yada T, Laybutt DR, Grey ST*, Herzog H*. Inhibition of Y1 receptor signaling improves islet transplant outcome. Nat Commun. 2017 Sep 8;8(1):490. PMID:2888756. *Grey is equal senior & co-corresponding author.

b. O'Connell PJ, Holmes-Walker DJ, Goodman D, Hawthorne WJ, Loudovaris T, Gunton JE, Thomas HE, Grey ST, Drogemuller CJ, Ward GM, Torpy DJ, Coates PT, Kay TW; Australian Islet Transplant Consortium. Multicenter Australian trial of islet transplantation: improving accessibility and outcomes. Am J Transplant. 2013 Jul;13(7):1850-8. PMID:23668890

c. Cowley MJ, Weinberg A, Zammit N, Walters SN, Hawthorne WJ, Loudovaris T, Thomas H, Kay T, Gunton JE, Alexander SI, Kaplan W, Chapman J, O'Connell PJ, Grey ST. Human islets express a marked pro-inflammatory molecular signature prior to transplantation. Cell Transplant. 2012 Mar 8. PMID:22404979

d. James Cantley, Stacey N Walters, Min-Ho Jung, Anita Weinberg, Mark J Cowley, Warren Kaplan, Wayne J Hawthorne, Philip J O’Connell, Gordon Weir, Shane T Grey. A pre-existent hypoxic gene signature predicts impaired islet graft function and glucose homeostasis. Cell Transplant. 2012 Oct 31. PMID:23127310.

4 – Grey has a developing expertise in cancer research and is building skills, knowhow and collaborative networks within this space. This capacity will support the feasibility and success of his new oncology program; supported by his newly minted NHMRC (~$1 million) Ideas grant. Preliminary data for the oncology program was generated by 2 sequential PanKind peer reviewed research grants.

a. Vennin C, Mélénec P, Rouet R, Nobis M, Cazet AS, Murphy KJ, Herrmann D, Reed DA, Lucas MC, Warren SC, Elgundi Z, Pinese M, Kalna G, Roden D, Samuel M, Zaratzian A, Grey ST, et al., Timpson P. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nat Commun. 2019 Aug 12;10(1):3637.

b. Chou A, Froio D, Nagrial AM, Parkin A, Murphy KJ, Chin VT, Wohl D, Steinmann A, Stark R, Drury A, Walters SN, Vennin C, Burgess A, Pinese M, Chantrill LA, Cowley MJ, Molloy TJ; Australian Pancreatic Cancer Genome Initiative (APGI), Waddell N, Johns A, Grimmond SM, Chang DK, Biankin AV, Sansom OJ, Morton JP, Grey ST, et al., Pajic M. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut. 2018 Dec;67(12):2142-215

c. Nobis M, Herrmann D, Warren SC, Kadir S, Leung W, Killen M, Magenau A, Stevenson D, Lucas MC, Reischmann N, Vennin C, Conway JRW, Boulghourjian A, Zaratzian A, Law AM, Gallego-Ortega D, Ormandy CJ, Walters SN, Grey ST, et al., Timpson, P. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts. Cell Rep. 2017 Oct 3;21(1):274-288.

d. Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, Del Monte-Nieto G, Conway JR, Nobis M, Allam AH, McCloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AA, Heu C, Nagrial AM, Chou A, Steinmann A, Drury A, Froio D, Giry-Laterriere M, Harris NL, Phan T, Jain R, Weninger W, McGhee EJ, Whan R, Johns AL, Samra JS, Chantrill L, Gill AJ, Kohonen-Corish M, Harvey RP, Biankin AV; Australian Pancreatic Cancer Genome Initiative (APGI), Evans TR, Anderson KI, Grey ST, et al., Timpson P. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med. 2017 Apr 5;9(384):

e. Erami Z, Herrmann D, Warren SC, Nobis M, McGhee EJ, Lucas MC, Leung W, Reischmann N, Mrowinska A, Schwarz JP, Kadir S, Conway JRW, Vennin C, Karim SA, Campbell AD, Gallego-Ortega D, Magenau A, Murphy KJ, Ridgway RA, Law AM, Walters SN, Grey ST, et al., Timpson P. Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue. Cell Rep. 2016 Jan 5;14(1):152-167.

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Location

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Biological Sciences North (D26) and South (E26) buildings

Contact

9295 8404

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ORCID as entered in ROS

https://orcid.org/0000-0003-2160-1625