Dr Sebastian Carotta

Details

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Division: Molecular Immunology

Research Overview

Common cancer therapies are often non-specific and ineffective in eradicating the cancer. To understand the mechanisms of how cancers arise and design more effective targeted therapies, a better understanding of how normal cell development is regulated is required.

The haematopoietic (blood) system due to its hierarchical organisation is an ideal system to study tissue development from normal stem cells and the formation of neoplasms such as leukaemias and lymphomas.

Differentiation of haematopoietic stem cells (HSC) and progenitors is under the strict control of a regulatory network orchestrated by the activity of key transcription factors. Detailed knowledge of these transcriptional networks is essential for a better understanding how blood homeostasis is regulated and how alterations in these networks lead to diseases such as cancer.

The main focus of our group is to understand how haematopoietic stem cell self-renewal versus lineage commitment is regulated on the molecular level and which pathways are critically dysregulated in the formation of leukaemias. To address these questions we are employing a range of different model systems such as mouse models, mouse and human embryonic stem cells.

Research Interests

Selected Publications

Carotta S, Pang S H, Nutt S L and Belz G T. Identification of the earliest NK-cell precursor in the mouse BM. Blood. 2011;117:5449-5452. PMID: 21422472
Vikstrom I, Carotta S, Luthje K, et al. Mcl-1 is essential for germinal center formation and B cell memory. Science. 2010;330:1095-1099. PMID: 20929728
Carotta S, Dakic A, D'Amico A, et al. The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. Immunity. 2010;32:628-641. PMID: 20510871
Naik SH, Sathe P, Park HY, Metcalf D, Proietto A, Dakic A, Carotta S, O’Keefe 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;8:1217-1226. PMID: 17922015
Holmes ML, Carotta S, Corcoran LM, Nutt SL. Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment. Genes Dev. 2006;20:933-938. PMID: 16618805
Pilat S, Carotta S, Schiedlmeier B, et al. HOXB4 enforces equivalent fates of ES-cell-derived and adult hematopoietic cells. Proc Natl Acad Sci U S A. 2005;102:12101-12106. PMID: 16093308
Carotta S, Pilat S, Mairhofer A, et al. Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells. Blood. 2004;104:1873-1880. PMID: 15166028

Reviews

Carotta S, Wu L, Nutt SL. Surprising new roles for PU.1 in the adaptive immune response. Immunol Rev. 2010;238:63-75. PMID: 20969585
Adams JM, Kelly PN, Dakic A, Carotta S, Nutt SL, Strasser A. Role of "cancer stem cells" and cell survival in tumor development and maintenance. Cold Spring Harb Symp Quant Biol. 2008;73:451-459. PMID: 19022754
Greig KT, Carotta S, Nutt SL. Critical roles for c-Myb in hematopoietic progenitor cells. Semin Immunol. 2008;20:247-256. PMID: 18585056
Carotta S, Nutt SL. Losing B cell identity. Bioessays. 2008;30:203-207. PMID: 18293359
Carotta S, Holmes ML, Pridans C, Nutt SL. Pax5 maintains cellular identity by repressing gene expression throughout B cell differentiation. Cell Cycle. 2006;5:2452-2456. PMID: 17102626

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Current Laboratory Members

Faculty Member: Sebastian Carotta PhD Vienna

Postdoctoral Fellow: Nicholas Huntington PhD Melb

Postdoctoral Fellow: Felix Zheng PhD Singapore

PhD Student: Milon Pang BSc(Hons) Melb BSc Murdoch (joint with Dr Stephen Nutt and Dr Li Wu)

PhD Student: Siavash Foroughi (joint with Professor Martin Pera, The University of Melbourne)

Research Assistant: Pradnya Gangatirkar MSc Nagpur India

The Walter and Eliza Hall Institute of Medical Research