Allergy Laboratory

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Professor Robyn O'Hehir


Professor Jennifer Rolland

Laboratory Heads

Professor Robyn O’Hehir
FRACP, PhD, FRCP, FRCPath
Email: robyn.ohehir@monash.edu
Email: r.ohehir@alfred.org.au
Phone: (03) 9076 2251

Professor Jennifer Rolland
Email: Jennifer.rolland@monash.edu
Phone: (03) 9903 0480

Department of Immunology
Monash University
AMREP
Melbourne 3004 Victoria
AUSTRALIA

Professor O’Hehir and Professor Rolland are the co-heads of the Allergy Research Laboratories in the Department of Immunology/ Department of Allergy, Immunology and Respiratory Medicine at Monash University. 

Allergy Research Group

Left to Right  - Back row: Jun Yao, Jeanne Lemasurier (PhD student), Astrid Voskamp, Neeru Varese, Dr Sara Prickett, Dr Angela Pizzolla, Dr Charles Hardy (Senior Research Fellow), Professor Robyn O'Hehir
Front row: Jess Anania (BMedSci Honours student), Tracy Phan, Jodie Abramovitch (PhD student), Rohimah Mohamud (PhD student), Professor Jennifer Rolland, Karen Symons (Research Nurse)

Biography - Professor Robyn O’Hehir

Professor Robyn O’Hehir has been a key international figure in allergy and asthma research and clinical care for over 25 years. She is an academic clinician scientist who successfully combines a strong track record in basic research with a clear commitment to clinical medicine, in this way demonstrating the value of translational medical research. The contribution of Professor O’Hehir to the allergy and respiratory field ranges from basic animal studies on the immunology of allergy and T cell epitope mapping, through translational research on novel immunogens designed to invoke protective immunity, to clinical research on the pathophysiology and management of asthma. She has more than 200 publications. The importance of her research is reflected by her success in competitive grant funding with an annual personal research budget in excess of $1.5 million. This includes continuous NHMRC funding (including 21 NHMRC or ARC grants over her career at Monash/Alfred since 1997) and a Co-operative Research Centre for Asthma and Airways. In 2007 she was honoured by the NHMRC in a publication as one of ten “Great Minds in Australian Research” and in 2010 was made a Life Governor of the Asthma Foundation of Victoria in recognition of 14 years service as a Director of Asthma Victoria. Professor O’Hehir also contributes to the community through membership of World Allergy Organisation committees, the Anaphylaxis and Asthma State Committees, the Food Standards Authority of Australia and New Zealand Scientific Committee and the Governing Board of Cabrini Health. Professor O’Hehir currently serves as Editor of the international journal Clinical and Experimental Allergy. She is regularly invited to give plenary and symposium keynote talks at national and international meetings. Professor O’Hehir is Director of the Department of Allergy, Immunology and Respiratory Medicine at The Alfred Hospital with 150 staff, studying and treating the full range of allergic and respiratory conditions. She is noted for offering the highest quality of leadership to a broadly based Department, with strong areas of basic research, clinical research, public health commitment and specialist clinical practice. She is actively engaged in national and international clinical trials, to ensure that her combined research and clinical duties focus on translation of research findings into improved Hospital and community clinical practice.

Biography - Emeritus Professor Jennifer Rolland

Professor Jennifer Rolland has a longstanding passion for research and education in basic and clinical immunology, with a special research focus on allergic diseases. She completed her BSc in Microbiology and Biochemistry at the University of Melbourne and her PhD in Immunology at Monash University. Together with Professor Robyn O’Hehir, she heads the Allergy Research Laboratories in the Department of Immunology, where the research scientists and students are well supported by strong clinical links ensuring clinically relevant and targeted research. Current projects focus on characterising the immune response to allergens, in particular the T cell response, with a view to developing safe and effective strategies for down-regulating allergic airway inflammation as well as reliable and non-invasive assays for monitoring allergic airways disease activity and response to treatment. The development of novel treatments for inflammatory lung disease is another major focus of the research group. The research is funded by the Cooperative Research Centre for Asthma and Allergy, the NH&MRC, the Ilhan Food Allergy Foundation, the CASS Foundation and the Alfred Research Trusts. Professor Rolland is an author on over 135 book chapters and journal articles and is Associate Editor for the international journal ‘Clinical and Experimental Allergy’.  She played a pivotal role in the development and delivery of the Department’s strong undergraduate and postgraduate programs in Immunology at Monash University and for several years she managed the diagnostic immunology service in the Department before this was incorporated into the adjoining Alfred Hospital pathology service for which she now acts as a consultant.  She is a member of the Immunology Fellowship Examinations panel for the Australian Institute of Medical Scientists, and is an active member of the Australian Society for Clinical Immunology and Allergy, and the Australian Society of Immunology. 

Research Interests and Projects

Elucidation of mechanisms for allergen-induced modulation of allergen-specific T cell responses
Sara Prickett, Tamara Etto, Astrid Voskamp, Neeru Varese in collaboration with Janet Davies, University of Queensland
Allergic diseases, including asthma, rhinitis and eczema, represent a major health burden worldwide.  Mainstay treatments are allergen avoidance where feasible and pharmacotherapy for symptom relief. For selected patients, allergen-specific immunotherapy (SIT) offers the prospect of long lasting clinical efficacy.  SIT involves the administration of allergen extract using a standardized regimen, usually subcutaneously or, increasingly, sublingually. However, application of this potentially curative treatment is restricted, largely due to the risk of serious adverse events, especially in asthmatics and for potent allergens such as peanut, seafood and latex. New insights into immunological mechanisms underlying effective SIT and molecular characterization of allergens and their recognition by the immune system suggest strategies for refinement of SIT. Selective targeting of allergen-specific T cells, especially regulatory T cells, is likely to be pivotal for efficacy.  We are investigating SIT induced changes in T cell response to allergen and in particular assays developed to identify the phenotype and function of different regulatory T cell subsets are being used to assess their induction during clinically successful immunotherapy.

Induction of regulatory T cell responses to inhibit ‘anaphylactic’-type immune responses to nut allergens (supported by Ilhan Food Allergy Foundation)
Sara Prickett, Astrid Voskamp, Neeru Varese, Tracy Phan

Peanut allergy is a life-threatening condition for many affected individuals world-wide.  There is currently no cure.  While whole allergen extracts are routinely used in specific immunotherapy for many respiratory and insect venom allergies, they can cause severe side effects and even fatalities in the case of peanut allergy.  Proof-of-concept studies demonstrate that short, T cell epitope-based peptides that target allergen-specific CD4+ T cells without triggering adverse IgE-mediated reactions are effective for allergen-specific immunotherapy for cat and bee venom allergy.  We aim to investigate options for developing a T cell-targeted peptide immunotherapy as a safe treatment for peanut allergy.  For this, multiple T cell lines recognizing the major peanut allergens Ara h 1 or Ara h 2 have been generated from a cohort of peanut-allergic individuals and sites of dominant T cell reactivity are being identified.  Suitable peptides for therapy will be those that can target pathogenic T cells in peanut-allergic subjects with a range of immunological genotypes, but do not contain IgE epitopes or activate basophils.  Clinical studies confirm that adults with peanut allergy often have coexistent allergy to tree nuts and sesame seeds. We will therefore test for T cell cross-reactivity between the selected peanut T cell epitope peptides and homologous peptides from tree nuts and sesame seeds.

Identification of suitable immunoregulatory preparations of clinically important Bahia grass pollen allergens for immunotherapy
Tamara Etto, Neeru Varese in collaboration with Janet Davies, University of Queensland

Bahia grass, Paspalum notatum, is a subtropical grass but now grown widely for domestic use and reported to trigger allergic rhinitis late in the pollen season in temperate regions.  We identified, cloned and sequenced the major group 1 and group 13 allergens of this pollen, Pas n 1 and Pas n 13. With the Pas n 1 sequence information, we have designed a nested set of 20-mer peptides spanning the entire sequence to identify sites of dominant T cell reactivity. Bahia grass pollen-reactive T cell lines are prepared from a panel of Bahia grass pollen-allergic subjects and tested for proliferative and cytokine responses to the 20-mer peptides. Core epitopes and MHC restriction of presentation of dominant sites are determined. Since Pas n 1 shows some IgE cross-reactivity with other grass pollen allergens, T cell cross-reactivity between the grass pollen allergens is also being investigated. Together these studies will inform selection of the appropriate mix of peptides for a safe and effective treatment of seasonal allergic rhinitis and asthma in a population.

The identification and characterisation of the major allergens in Australian crustacean species
Neeru Varese, Astrid Voskamp, Jodie Abramovitch in collaboration with Andreas Lopata and Sandip Kamath, John Curtin University, Queensland 

The increase in prevalence and potential fatality of food allergy has led to increased efforts to find more specific diagnostic assays as well as effective therapies and prophylactic measures. More than 90 percent of allergic reactions can be attributed to exposure to foods, including fish and shellfish. The shellfish group includes crustaceans (prawns, lobsters, crabs) and molluscs (oysters, mussels, abalone). Very few shellfish allergens have been characterised on a molecular level. In this project, we are performing a detailed characterisation of the shared and unique allergens of different shellfish to accurately predict clinically significant cross-allergy among the different groups. The effects of food processing (eg heating) and digestion on allergenicity of shellfish proteins is also being determined.  This research will inform the development of a microarray diagnostic for shellfish allergy leading to improved diagnosis and management of these patients.

Activin A and Follistatin in airway inflammation
Charles Hardy, John Yao, Hong-An Nguyen

Activin A and Follistatin are naturally occurring substances with roles in normal tissue function, maturation and repair. Follistatin is an endogenous negative regulator of Activin A.  Recent evidence suggests that activin A regulates proinflammatory cytokine production and is itself regulated by inflammatory mediators. Our studies using murine models of allergic airway inflammation and cystic fibrosis suggest that Activin A plays an important role in inflammatory lung pathogenesis.  We are further investigating the proinflammatory effects of Activin A and evaluating potential inhibitors including follistatin using murine and clinical samples.  These studies have important implications for monitoring disease activity and developing new therapeutic approaches. 

Nanoparticles to induce lung resistance to airway inflammation
Charles Hardy, John Yao, Jeanne LeMasurier, Rohimah Mohamud, in collaboration with Prof Magdalena Plebanski

Using a murine allergy model, we made the unexpected finding that inert ultrafine nanoparticles when instilled into the airways prevented allergic airway inflammation.  Importantly, the nanoparticles did not have a broad immunosuppressive effect as there was no effect on induction of serum allergen-specific IgE or Th2 cytokine producing cells in the spleen at the time of allergen sensitisation.  Rather the effect was on local (lung) response to allergen rechallenge. Current research is defining the particle characteristics and the immune basis for this novel anti-inflammatory effect.

Staff List:

Senior Research Fellow

• Dr Charles Hardy

Research Fellows

• Dr Sara Prickett
• Thomas Oh

Research Assistants

• Jodie Abramovich
• Neeru Varese
• Astrid Voskamp
• John Yao
• Tracy Phan

PhD Students

• Hong-An Nguyen
• Rohimah Mohamud
• Jeanne LeMasurier (joint with Prof Magdalena Plebanski)

Hons Student

• Jodie Abramovitch

Research Nurses

• Karen Symons
• Kirsten Deckert
• Lorraine Baxter

Clinical Research Fellows/Specialists

• Dr Andrew Gillman
• Alessandra Sandrini
• Dr Celia Zubrinich

Selected Publications:

1. Glaspole IN, de Leon MP, Prickett SR, O’Hehir RE, Rolland JM. (2011) Clinical allergy to hazelnut and peanut: identification of T cell cross-reactive allergens”. Int Arch Allergy Immunol 155:345-54
   
2. Davies JM, Voskamp A, Thanh DD, Petit B, Loo D, Petersen A, Hill MM, Upham JW, Rolland JM, O’Hehir RE. (2011) The dominant 55 kDa allergen of the subtropical Bahia grass (Paspalum notatum) pollen is a group 13 pollen allergen, Pas n 13.  Mol Immunol 48:931-40
3. Davies JM, Thanh DD, Voskamp A, Drew AC, Biondo M, Phung M, Upham JW, Rolland JM, O’Hehir RE. (2011) Functional immunoglobulin E cross-reactivity between Pas n 1 of Bahia grass pollen and other group I grass pollen allergens. Clin Exp Allergy 41:281-91
4. Prickett SR, Voskamp AL, Dacumos-Hill A, Symons K, Rolland JM, O’Hehir RE. (2011)  Ara h 2 peptides comprising dominant CD4+ T-cell epitopes: candidates for a peanut allergy therapeutic. J Allergy Clin Immunol 127:608-15
5. Drew A, Davies JM, Dang TD, Rolland JM, O’Hehir RE. (2011) Purification of the major group 1 allergen from Bahia grass pollen, Pas n 1. Int Archiv Allergy Immunol. 154: 295-8
6. Rolland JM, Gardner LM, O’Hehir RE. (2010)  Functional regulatory T cells and allergen immunotherapy. Curr Opin Allergy Clin Immunol 10: 559-66.
7. Walton SF, Pizzutto S, Slender A, Viberg L, Holt D, Belinda J Hales BJ, Kemp DJ, Currie BJ, Rolland JM, O’Hehir RE. (2010) Increased allergic immune response to Sarcoptes scabiei antigens in crusted versus ordinary scabies.  Clin Vac Imm 17: 1428-38
8. Mittag D, Scholzen A, Varese N, Baxter L, Paukovics G, Harrison L, Rolland JM & O'Hehir RE. (2010) The effector T cell response to ryegrass pollen is counter-regulated by simultaneous induction of regulatory T cells. J Immunol 184: 4708-16
9. O'Hehir RE, Gardner LM, de Leon MP, Hales BJ, Biondo M, Douglass JA, Rolland JM, Sandrini A. (2009) House Dust Mite Sublingual Immunotherapy - The Role for TGF-beta and Functional Regulatory T Cells. Am J Respir Crit Care Med 180:936-47
10. Hardy CL, LeMasurier JS, Olsson F, Dang T, Yao J, Yang M, Plebanski M, Phillips DJ, Mollard RA, Rolland JM, O’Hehir RE. (2010) IL-13 regulates secretion of the TGF-beta superfamily cytokine Activin-A in allergic airway inflammation. Am J Resp Cell Mol 42:667-75
11. Rolland JM, Gardner LM, O’Hehir RE. (2009) Allergen-related approaches to immunotherapy.  Pharmacol Ther 121:273-84
12. Davies JM, Mittag D, Dang TD, Symons K, Voskamp A, Rolland JM, O’Hehir RE. (2008) Molecular cloning, expression and immunological characterisation of Pas n 1, the major allergen of Bahia grass Paspalum notatum pollen.  Mol Immunol 46: 286-93
    
13. Rolland JM, O’Hehir RE. (2008) Latex allergy: a model for therapy.  State of the Art Review.  Clin Exp Allergy 38:898-912
14. de Leon MP, Rolland JM, O’Hehir RE. (2007) The peanut allergy epidemic: allergen molecular characterization and prospects for specific therapy. Expert Rev Mol Med 9:1-18