Dr Hongjun SHI received his Bachelor of Biomedical Sciences degree in Human  Genetics (1st class honors) from Victoria University of Wellington in 2006, and  PhD in Pathology from University of Otago in 2012. After his PhD, he joined  Victor Chang Cardiac Research Institute at Sydney as a post-doctoral scientist   and conjoint lecturer at University of New South Wales. In 2017, he accepted  the Assistant Professor position at Westlake University. His research interest  is to understand the molecular mechanisms of cardiac development and congenital  heart disease.

Congenital  heart disease (CHD) is the most common form of birth defects accounting for ~1%  of all new born.  Currently only about 20-30% of CHD cases have identifiable  genetic or environmental explanations. The majority of CHD arise from unknown  causes, reflecting our poor understanding of the pathophysiology of this  disease. At Victor Chang Cardiac Research Institute, Dr Shi analyzed the whole  genome sequences of a number of CHD families, and identified several  mutations  in the NAD biosynthesis pathway that disrupt niacin metabolism and cause energy  crisis in the developing embryos, resulting multiple congenital malformations  including Hypoplastic Left Heart Syndrome-the most severe form of CHD. Dr Shi  also found certain environmental insults, such as gestational hypoxia, anemia,  and certain prescription drug uses, induce hypoxia and ER stress in the  developing heart, resulting CHD. Importantly, these environmental factors may  interact with mutations in the key cardiac regulatory genes such as those in FGF  and NOTCH signaling pathways, significantly increasing both the severity and  penetrance of the heart defects. At Westlake University, Dr Shi continues to  investigate the molecular mechanism regulating the heart development and strive  to uncover the novel etiology of CHD.  His ultimate goal is to establish a more  effective tool for the diagnosis and prevention of this disease.

Team

Dr  Xiangyang Liu (Research Scientist)

Mr  Yunfei Mu (PhD student)

Ms  Xiaoxi Luo (PhD student)

Ms  Yaqi Lu (Research Assistant)

Mr  Jianfeng Wang (Research Assistant)

Ms  Qian Chen (Research Assistant)

Ms  Youshi Chen (Animal technician)

1. Hartmut Cuny, Melissa Rapadas, Jessica Gereis, Ella M. M. A. Martin, Rosemary B. Kirk, Hongjun Shi, Sally L. Dunwoodie. NAD deficiency due to environmental factors or gene–environment interactions causes congenital malformations and miscarriage in mice. Proceedings of the National Academy of Sciences Feb 2020, 117 (7) 3738-3747

2. Gavin Chapman, Julie L M Moreau, Eddie Ip, Justin O Szot, Kavitha R Iyer, Hongjun Shi, Michelle X Yam, Victoria C O’Reilly, Annabelle Enriquez, Joelene A Greasby, Dimuthu Alankarage, Ella M M A Martin, Bernadette C Hanna, Matthew Edwards, Steven Monger, Gillian M Blue, David Winlaw, Helen E Ritchie, Stuart M Grieve, Eleni Giannoulatou, Duncan B Sparrow, Sally L Dunwoodie. (2019) Functional genomics and gene-environment interaction highlight the complexity of Congenital Heart Disease caused by Notch pathway variants. Human Molecular Genetics. 13;29(4):566-579

3. Liu Y, Wang L, Shi H. The biological function of ELABELA and APJ signaling in the cardiovascular system and pre-eclampsia. (2019) Hypertension research. Jul;42(7):928-934.

4. Shi, H., Enriquez, A., Rapadas, M., Martin, E.M.M.A., Wang, R., Moreau, J., Lim, C.K., Szot, J.O., Ip, E., Hughes, J.N., Sugimoto, K., Humphreys, D.T., McInerney-Leo, A.M., Leo, P.J., Maghzal, G.J., Halliday, J., Smith, J., Colley, A., Mark, P.R., Collins, F., Sillence, D.O., Winlaw, D.S., Ho, J.W.K., Guillemin, G.J., Brown, M.A., Kikuchi, K., Thomas, P.Q., Stocker, R., Giannoulatou, E., Chapman, G., Duncan, E.L., Sparrow, D.B., Dunwoodie, S.L., 2017. NAD Deficiency, Congenital Malformations, and Niacin Supplementation. New England Journal of Medicine 377, 544-552.

5. Shi, H., O'Reilly, V.C., Moreau, J.L., Bewes, T.R., Yam, M.X., Chapman, B.E., Grieve, S.M., Stocker, R., Graham, R.M., Chapman, G., Sparrow, D.B., Dunwoodie, S.L., 2016. Gestational stress induces the unfolded protein response, resulting in heart defects. Development 143, 2561-2572.

6. McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., and Duncan, E. L. (2015) Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects, Human molecular genetics 24, 1234-1242.

7. Besic, V., Shi, H., Stubbs, R. S., and Hayes, M. T. (2015) Aberrant liver insulin receptor isoform a expression normalises with remission of type 2 diabetes after gastric bypass surgery, PloS one 10, e0119270.

8. O'Reilly, V. C., Lopes Floro, K., Shi, H., Chapman, B. E., Preis, J. I., James, A. C., Chapman, G., Harvey, R. P., Johnson, R. S., Grieve, S. M., Sparrow, D. B., and Dunwoodie, S. L. (2014) Gene-environment interaction demonstrates the vulnerability of the embryonic heart, Developmental biology 391, 99-110.

9. Moreau, J. L., Artap, S. T., Shi, H., Chapman, G., Leone, G., Sparrow, D. B., and Dunwoodie, S. L. (2014) Cited2 is required in trophoblasts for correct placental capillary patterning, Developmental biology 392, 62-79.

10.Shi, H., Hayes, M. T., Kirana, C., Miller, R. J., Keating, J. P., and Stubbs, R. S. (2013) Overexpression of aminoacylase 1 is associated with colorectal cancer progression, Human pathology 44, 1089-1097.

11. Shi, H., Hayes, M., Kirana, C., Miller, R., Keating, J., Macartney-Coxson, D., and Stubbs, R. (2012) TUFM is a potential new prognostic indicator for colorectal carcinoma, Pathology 44, 506-512.

12. Kirana, C., Shi, H., Laing, E., Hood, K., Miller, R., Bethwaite, P., Keating, J., Jordan, T. W., Hayes, M., and Stubbs, R. (2012) Cathepsin D Expression in Colorectal Cancer: From Proteomic Discovery through Validation Using Western Blotting, Immunohistochemistry, and Tissue Microarrays, International journal of proteomics  245819.

13. Shi, H., Hood, K. A., Hayes, M. T., and Stubbs, R. S. (2011) Proteomic analysis of advanced colorectal cancer by laser capture microdissection and two-dimensional difference gel electrophoresis, Journal of proteomics 75, 339-351.

14. Shi, H. J., Stubbs, R., and Hood, K. (2009) Characterization of de novo synthesized proteins released from human colorectal tumour explants, Electrophoresis 30, 2442-2453.

15. Kirana, C., Ward, T., Jordan, T. W., Rawson, P., Royds, J., Shi, H. J., Stubbs, R., and Hood, K. (2009) Compatibility of toluidine blue with laser microdissection and saturation labeling DIGE, Proteomics 9, 485-490.

16. Macartney-Coxson, D. P., Hood, K. A., Shi, H. J., Ward, T., Wiles, A., O'Connor, R., Hall, D. A., Lea, R. A., Royds, J. A., Stubbs, R. S., and Rooker, S. (2008) Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level, BMC cancer 8, 187.