The Walter and Eliza Hall Institute of Medical Research

Professor Ken Shortman

Details

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Division: Immunology

Research Overview

Our general interest is in the development and function of cells of the immune defense system. Our specific focus is on dendritic cells (DC), whose central function is the collection, processing and presentation of antigenic material to T lymphocytes. Depending on the information the DC have received from the normal environment, or from microbial infections or tissue damage, the DC determine whether the resultant T cell response leads to immune tolerance, or to an appropriate type of immune response. Thus, although they are a numerically minor cellular component of the immune system, DC have a key regulatory role. Our previous studies had shown that the DC network consists of a series of discrete DC subtypes, sharing these common features but specialised for functioning in different locations and for inducing different types of immune responses.

Our current research has three objectives. The first is to understand how these specialised types of DC develop from bone marrow stem cells, since they represent the last pathway of haematopoiesis to be mapped. The second is to identify DC surface molecules involved in DC signaling functions, then to use these molecules as targets to manipulate immune responses and improve the effectiveness of vaccines. Since most of our information is obtained from research on mice, the final objective is to compare the mouse and human DC systems and find common links, so detailed information from the mouse studies can be translated to clinical application.

Research Interests

• Mapping the pathways of development of the specialised DC subtypes
• Identification of novel DC surface molecules and using them to modulate immune responses
• Identification of subtypes of human DC and comparing them to mouse DC

Selected Publications

1. Naik, S.H., Metcalf, D., van Nieuwenhuijze, A., Wicks, I., Wu, L., O'Keeffe, M., and Shortman, K. 2006. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 7:663-671.
2. Naik S.H., Sathe P., Park H.Y., Metcalf D., Proietto A., Dakic A., Carotta S., O'Keeffe M., Bahlo M., Papenfuss A., Kwak J.Y., Wu L., and Shortman K. 2007. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 8:1217-1226.
3. Caminschi,I., Proietto,A.I., Ahmet,F.,Kitsoulis,S., Shin, T.J., Lo,J,C., Rizzitelli,A., Wu,L., Vremec,D., van Dommelen, S.L., Campbell,I.K., Maraskovsky,E., Braley,H., Davey,G.M., Mottram,P., van de Velde,N., Jensen,K., Lew,A.M., Wright,M.D., Heath,W.R., Shortman,K., and Lahoud,M.H. 2008. The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood 112:3264-3273.
4. Shortman K, Liu YJ. Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002 Mar;2(3):151-61 PMID: 11913066 [PubMed - indexed for MEDLINE]
5. Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, Dakic A, Carotta S, O'Keeffe M, Bahlo M, Papenfuss A, Kwak JY, Wu L, Shortman K. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol. 2007 Nov;8(11):1217-26 PMID: 17922015 [PubMed - indexed for MEDLINE]
6. Shortman K, Naik SH. Steady-state and inflammatory dendritic-cell development. Nat Rev Immunol. 2007 Jan;7(1):19-30 PMID: 17170756 [PubMed - indexed for MEDLINE]
7. Caminschi I, Ahmet F, Heger K, Brady J, Nutt SL, Vremec D, Pietersz S, Lahoud MH, Schofield L, Hansen DS, O'Keeffe M, Smyth MJ, Bedoui S, Davey GM, Villadangos JA, Heath WR, Shortman K. Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells. J Exp Med. 2007 Oct 29;204(11):2579-90 PMID: 17923506 [PubMed - indexed for MEDLINE]
8. Caminschi I, Proietto AI, Ahmet F, Kitsoulis S, Shin Teh J, Lo JC, Rizzitelli A, Wu L, Vremec D, van Dommelen SL, Campbell IK, Maraskovsky E, Braley H, Davey GM, Mottram P, van de Velde N, Jensen K, Lew AM, Wright MD, Heath WR, Shortman K, Lahoud MH. The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood. 2008 Oct 15;112(8):3264-73 PMID: 18669894 [PubMed - indexed for MEDLINE]

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Current Laboratory Members

Faculty Member: Ken Shortman, BSc(Hons) Syd PhD Melb FAA

Senior Postdoctoral Fellow: Irene Caminschi, BSc(Hons) Murdoch, PhD UWA

Senior Postdoctoral Fellow: Mireille Lahoud, BSc Mon BSc(Hons) Melb PhD Mon

Research Assistant: Fatma Ahmet, BSc(Hons) Melb

Research Assistant: Jacinta Grayden, BSc(Hons) Mon

Research Assistant: Susie Kitsoulis, BSc Mon

Research Assistant: Soo San Wan, BAgSc(Hons) MAgSc LaT

Research Assistant: David Vremec, BAppSc RMIT

PhD Student: Priyanka Sathe, BSc Syd BSc(Hons) Melb

Honours Student: Antonia Policheni, BSc Monash