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Professor NICHOLLS John M | nicholls@pathology.hku.hk
Professor
MBBS Adel; FRCPA; FHKCPath; FHKAM (Pathology)

How do viruses interact with cells?
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Research Description

Viruses are involved in a number of infectious and neoplastic diseases of the respiratory tract in humans. I have been investigating what role the Epstein-Barr virus plays in nasopharyngeal carcinoma (NPC), and in particular two of the viruses proteins (LMP1 and BARF1) which have been implicated in the development of NPC. In particular I have been looking at whether there is “good” or “bad” LMP or BARF1 and how these proteins differ in NPCs from different geographical regions This work involves collaboration with EBV experts from Europe and North America.

In addition I have worked closely with colleagues from the Department of Microbiology in investigating why certain new and emerging viruses such as SARS and H5N1 appear to be so lethal in humans. Is it because they are attacking cells which are not normally attacked by viruses? Is it because they are triggering cells to release too many cytokines, or is it because they are interacting with cell receptors which are not normally expressed in normal conditions? Whatever the results, the main aim of my research is to put a clinical perspective on reducing the damage caused by viruses in the human.

Biography

Professor John Nicholls is a Clinical Professor in Pathology at the University of Hong Kong. He commenced medical studies at the University of Adelaide, South Australia in 1977 and graduated in 1983. He commenced postgraduate training in pathology at the Institute of Medical and Veterinary Sciences, the Queen Elizabeth Hospital and The Adelaide Children’s Hospital. In 1988 he moved to Hong Kong as a Lecturer in Pathology at the University of Hong Kong where in addition to clinical and teaching duties commenced research into the relationship of viruses with the respiratory tract. His publications were focused on the role of Epstein-Barr Virus in nasopharyngeal carcinoma, a common tumour in the Guangdong region.

In 1997, following the first outbreak of H5N1 influenza in humans, he commenced collaboration with the Department of Microbiology to study the pathological effects of avian influenza viruses in the respiratory tract. In 2003 he was a key member of the research team at the University of Hong Kong which isolated and characterized the novel SARS coronavirus which was associated with the global outbreak of 2003.

His work on SARS and avian influenza has been published in prestigious journals such as Lancet, PLOS Medicine and Nature Medicine as listed in part of his selected biography. His current investigative work is looking at the viral binding sites in the respiratory tract and determining susceptibility to avian influenza in humans and other animals. Together with staff from the School of Public Health he has established a lung and bronchial ex vivo culture system to investigate tropism and pathogenesis of emerging viral infections, as well as potential novel antiviral agents such as DAS181 in these systems. In 2009 he was awarded a Croucher Senior Medical Fellowship to work on novel therapeutic strategies for influenza.

Awards and Honours

University Teaching Fellowship (1997-98)

Medical Education

Selected Publications

Researcher Profile on HKU Scholars Hub

Walther T, Karamanska R, Chan RW, Chan MC, Jia N, Air G, Hopton C, Wong MP, Dell A, Malik Peiris JS, Haslam SM, Nicholls JM. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog. 2013 Mar;9(3):e1003223.

Chan MC, Chan RW, Yu WC, Ho CC, Yuen KM, Fong JH, Tang LL, Lai WW, Lo AC, Chui,WH, Sihoe AD, Kwong DL, Wong DS, Tsao GS, Poon LL, Guan Y, Nicholls JM, Peiris, JS. Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract. AM J PATHOL. 2010 Apr;176(4):1828-40.

Nicholls, JM; Bourne, AJ; Chen, H; Guan, Y; Peiris, JSM. 2007. Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses. RESPIRATORY RESEARCH 8: art. no.-73

Nicholls, JM; Chan, MCW; Chan, WY; Wong, HK; Cheung, CY; Kwong, DLW; Wong, MP; Chui, WH; Poon, LLM; Tsao, SW; Guan, Y; Peiris, JSM. 2007. Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. NATURE MEDICINE 13 (2): 147-149.

Nicholls, JM; Poon, LLM; Lee, KC; Ng, WF; Lai, ST; Leung, CY; Chu, CM; Hui, PK; Mak, KL; Lim, W; Yan, KW; Chan, KH; Tsang, NC; Guan, Y; Yuen, KY; Peiris, JSM. 2003. Lung pathology of fatal severe acute respiratory syndrome. LANCET 361 (9371): 1773-1778.

Chan RW, Chan MC, Agnihothram S, Chan LL, Kuok DI, Fong JH, Guan Y, Poon LL, Baric RS, Nicholls JM, Peiris JS. Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. J Virol. 2013 Jun;87(12):6604-14.

Chan MC, Chan RW, Chan LL, Mok CK, Hui KP, Fong JH, Tao KP, Poon LL, Nicholls JM, Guan Y, Peiris JM. Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract. Lancet Respir Med. 2013 Sep;1(7):534-42

Chan RW, Karamanska R, Van Poucke S, Van Reeth K, Chan IW, Chan MC, Dell A, Peiris JS, Haslam SM, Guan Y, Nicholls JM. Infection of swine ex vivo tissues with avian viruses including H7N9 and correlation with glycomic analysis. Influenza Other Respir Viruses. 2013 Nov;7(6):1269-82.

Triana-Baltzer GB, Babizki M, Chan MC, Wong AC, Aschenbrenner LM, Campbell ER, Li QX, Chan RW, Peiris JS, Nicholls JM, Fang F. DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis. J Antimicrob Chemother. 2010 Feb;65(2):275-84. doi: 10.1093/jac/dkp421. Epub 2009 Nov 26.

Haselhorst T, Garcia JM, Islam T, Lai JC, Rose FJ, Nicholls JM, Peiris JS, von Itzstein M. Avian influenza H5-containing virus-like particles (VLPs): host-cell receptor specificity by STD NMR spectroscopy. Angew Chem Int Ed Engl. 2008;47(10):1910-2. doi: 10.1002/anie.200704872.