Dr Tihana Bicanic is a Reader and honorary Consultant in infectious diseases. Her research interests are in the fungus Cryptococcus neoformans which causes cryptococcal meningitis.
She has performed clinical trials of combination antifungal therapy in HIV-associated cryptococcal meningitis at the University of Cape Town, South Africa, and now focuses on the contribution of cryptococcal variation to clinical disease and outcome in humans.
Dr Bicanic’s research training and interest is in Cryptococcus and cryptococcal meningitis, as part of the Cryptococcal Meningitis Group at St George’s. For her MD(Res) degree at St George’s, she performed clinical trials of combination antifungal therapy in HIV-associated cryptococcal meningitis at the University of Cape Town, South Africa, with Professor Tom Harrison. These generated a large number of cryptococcal isolates linked to clinical data, which form the focus of her current research on the contribution of variation in the properties of the infecting cryptococcal strain to clinical presentation and outcome in human cryptococcosis.
Dr Bicanic’s Wellcome Intermediate Fellowship focussed on the relationship of the C neoformans capsule, arguably the organism’s most important virulence factor, with development of raised intracranial pressure and host immune response. Studies on the ex vivo cryptococcal capsule were undertaken within the NIH-funded Cryptococcal Optimal ART Timing Trial (COAT).
Her group have described the association of other notable cryptococcal virulence factors - melanisation, macrophage parasitism and survival in human cerebrospinal fluid, with presentation and outcome in human infection. Her group has also examined the relationship of cryptococcal genotype (by multilocus sequence typing) and outcome. In collaboration with Professor Matthew Fisher at Imperial, they have completed whole genome sequencing of >300 clinical and environmental isolates to explore the genetic basis of virulence in Cryptococcus.
Recently, Dr Bicanic has also been awarded a postdoctoral fellowship project award through a Wellcome Trust Stretegic Award in Medical Mycology and Fungal Immunology (WTSA MMFI), to look at the human immunogenetics of susceptibility to, and severity of, cryptococcal meningitis in patients with advanced HIV (2013), as well as a WTSA MMFI clinical fellowship award to look at the relationship between antifungal PK/PD and resistance and microbiologic outcome in patients treated with fluconazole-based regimens for cryptococcal meningitis (2014).
She is a co-investigator on the phase III Advancing Cryptococcal meningitis treatment trial. Together with other members of the group and partners from the World Health Organisation, Centers for Disease Control, Medecins Sans Frontieres, and others, she is involved in advocacy to improve access to antifungals in developing countries.
Dr Bicanic joined St George’s as a Senior Lecturer and Honorary Consultant in Infectious Diseases in April 2013. Prior to this she undertook her pre-clinical medical training at Cambridge and clinical training at Oxford. Dr Bicanic’s specialist postgraduate clinical training in microbiology and infectious diseases was based at St George’s Hospital NHS Trust (2002-2009).
Dr Bicanic’s interest in infectious diseases research emanated from a three-month research visit to the Mahidol-Oxford University Tropical Medicine Research Unit in Thailand in 2001, where she assisted with studies in meliodosis and malaria. She subsequently spent time at the Albert Schweitzer Hospital in Lambaréné, Gabon, investigating the pathophysiology of malaria (with Professor Sanjeev Krishna).
Since 2004, together with Professor Tom Harrison, she has been involved in clinical and translational research in the field of cryptococcal meningitis in HIV, and since 2010 has had her own cryptococcal laboratory and research group at St George’s. She was promoted to Reader in Infectious Diseases in October 2015.
Selected recent publications
Beale MA, Sabiiti W, Robertson EJ, Fuentes-Cabrejo KM, O’Hanlon SJ, Jarvis JN, Loyse A, Meintjes G, Harrison TS, May RC, Fisher MC, Bicanic T. Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa. PLoS Negl Trop Dis 2015 9(6): e0003847.
Jarvis JN, Meintjes G, Bicanic T, Buffa V, Hogan L, et al. (2015) Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis. PLoS Pathog 11(4): e1004754
Sabiiti W, Robertson E, Beale MA, Johnston SA, Brouwer AE, Loyse A, Jarvis JN, Gilbert AS, Fisher MC, Harrison TS, May RC, Bicanic T. Efficient phagocytosis and laccase activity affect outcome of HIV-associated cryptococcosis. J Clin Inv 2014 May 1;124(5):2000-8.
Chen Y, Toffaletti DL, Tenor JL, Litvintseva AP, Fang C, Mitchell TG, McDonald TR, Nielsen K, Boulware DR, Bicanic T, Perfect JR. The Cryptococcus neoformans transcriptome at the site of human meningitis. MBio 2014 Feb 4;5(1):e01087-13
Jarvis JN*, Bicanic T* (*joint first authors), Loyse A, Namarika D, Jackson A, Nussbaum JC, Longley N, Muzoora C, Phulusa J, Taseera K, Kanyembe C, Wilson D, Hosseinipour MC, Brouwer AE, Limmathurotsakul D, White N, van der Horst C, Wood R, Meintjes G, Bradley J, Jaffar S, Harrison T. Determinants of Mortality in a Combined Cohort of 501 Patients with HIV-associated Cryptococcal Meningitis: Implications for Improving Outcomes. Clin Infect Dis 2014 Mar;58(5):736-45.
Robertson EJ, Najjuka G, Rolfes MA,Akampurira A, Jain N, Anantharanjit J, von Hohenburg M, Tassieri M, Carlsson A, Meya DB, Harrison TS, Fries B, Boulware DR, Bicanic T. Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. J Infect Dis 2014 Jan 1;209(1):74-82.
Patel S, Shin GY, Wijewardana I, Vitharana SR, Cormack I, Pakianathan M, Harrison TS, Bicanic T. The prevalence of cryptococcal antigenemia in newly diagnosed HIV patients in a Southwest London cohort, J Infect 2013 Jan;66(1):75-9
Loyse A, Thangaraj H, Easterbrook P, Ford N, Roy M, Chlller T, Govender N, Harrison TS, Bicanic T. Cryptococcal meningitis: improving access to essential antifungal medicines in developing countries. Lancet Infect Dis. 2013 Jul;13(7):629-37
Selected prior publications
Bicanic T; Wood R; Meintjes G; Rebe K; Brouwer A; Loyse A; Bekker LG; Jaffar S; Harrison T. High dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV: a randomised trial. Clin Infect Dis 2008 Jul 1; 47(1): 123-130
Bicanic T; Brouwer AE; Meintjes, G; Rebe K, Limmathurotsakul D, Chierakul W, Teparrakkul P, Loyse A, White NJ, Wood R, Jaffar S and Harrison TS. Relationship of CSF pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS 2009 23 (6): 701-706
Bicanic T, Muzoora C, Brouwer A, Meintjes G, Longley N, Taseera K, Rebe K, Loyse A, Jarvis JN, Bekker LG, Wood R, Limmathurotsakul D, Chierakul W, Stepniewska K, White NJ, Jaffar S, Harrison TS. Rate of clearance of infection is independently associated with clinical outcome in HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clin Infect Dis 2009 49(5): 702-709
Dr Mathew Beale, postdoctoral research assistant
Dr Shichina Kannambath, postdoctoral research assistant
Dr Neil Stone, PhD student
Dr David Boulware, University of Minnesota, USA
C. neoformans phenotype and gene expression: effects on raised CSF pressure and clinical outcomes.
Professor Robin May, University of Birmingham
Correlation of C neofomans virulence in macrophage models and clinical parameters and outcomes.
Professor Matthew Fisher, Imperial College, London
Role of cryptococcal pathogen diversity (by MLST sequence typing) in cryptococcal pathogenesis.
Professor Peter Williamson, National Institutes of Health, USA
In vitro gene expression in C neoformans.
Professor Mihai Netea, UMC St Radboud, Nijemegen, Netherlands
Host genetic susceptibility to cryptococcosis.
Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology, Clinical Fellowship to Dr Neil Stone: The relationship of antifungal resistance and pharmacokinetics with therapeutic response to a fluconazole/flucytosine induction regimen for HIV-associated Cryptococcal meningitis.
Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology: Postdoctoral award: Host genetic susceptibility to cryptococcosis.
Gilead UK and Ireland Fellowship: Antifungal stewardship and novel Aspergillus diagnostics.
Co-Applicant, MRC research grant: An evolutionary population genomics approach to determine the genetic basis of virulence in the pathogenic fungus Cryptococcus neoformans (PI Matthew Fisher, Imperial College).
Wellcome Trust Intermediate Fellowship: The impact of C neoformans phenotype and genotype on the clinical course and outcome of human cryptococcal meningitis.