Michelle Haber

Last updated

Michelle Haber
Born
NationalityAustralian
Alma mater University of New South Wales
Known forIdentifying molecular targets in neuroblastoma and developing novel therapeutic approaches against them
AwardsDoctor of Science honoris causa, UNSW (2008)
Scientific career
FieldsPaediatric cancer
Institutions

Michelle Haber AM FAA FAHMS is an Australian cancer researcher in the field of childhood cancer research.

Contents

Early life and education

Michelle Haber was born in Liverpool, England.[ citation needed ]

Haber attended Mount Scopus Memorial College in Melbourne and, when her family moved to Sydney, attended Moriah College, graduating in 1973.[ citation needed ]

She completed a clinical psychology degree at University of New South Wales and was awarded a University Medal. She obtained her PhD from the School of Pathology at the University of New South Wales in 1984 - her thesis was entitled "Structural analysis by BD-cellulose chromatography of mammalian DNA during repair, replication and degradation". [1]

Career

In 1982, during her PhD studies, Haber spent three months as Visiting Research Fellow at the Department of Molecular Virology in Hadassah Medical Centre, Hebrew University of Jerusalem. Her first postdoctoral position was as at Children’s Leukaemia and Cancer Research Unit, a precursor to Children's Cancer Institute then located at the Prince of Wales Children’s Hospital, Randwick. Having joined as a Staff Scientist in 1984, [2] she was promoted to Senior Research Fellow in 1992, Principal Research Fellow in 1996, Director in 2000 [2] and Executive Director in 2003. [2] Haber also holds a conjoint appointment as Professor in the Faculty of Medicine at the University of New South Wales. [3]

She serves as the executive director of Children's Cancer Institute [4] and is a professor at the School of Women’s and Children’s Health, University of New South Wales. [5] She is known for her discoveries in the area of chemotherapy resistance in neuroblastoma and for translating these discoveries into new therapeutics that are currently in clinical trials. [6]

Under her leadership Children's Cancer Institute, now located in the UNSW Lowy Cancer Research Centre, [7] has tripled in size and grown from a little known group to become the largest children’s cancer research facility in the region. [8]

Research

Haber’s early studies were amongst the first characterising the complex molecular mechanisms underlying therapy-related drug resistance. [9] [10] With her collaborators, she identified the relationship between high expression of multidrug transporter gene MRP1, and the malignant phenotype of neuroblastoma and poor clinical outcome. [11] [12] These studies provided the first definitive demonstration of clinical relevance of the MRP1 gene in solid tumours, resulting in a large international clinical study which confirmed the independent prognostic significance of MRP1 expression in neuroblastoma and established MRP1 inhibition as a potential new treatment for this disease. [13]

By high-throughput chemical screening of small molecule libraries, Haber and her colleagues have also developed novel MRP1 inhibitors and patented and licensed the compounds for the treatment of neuroblastoma and other MRP1-associated malignancies. This led to a $3.1M award from the Australian Cancer Research Foundation to establish a Drug Discovery Centre for Childhood Cancer in the UNSW Lowy Cancer Research Centre, which is currently developing a pipeline of potential new drugs for treating childhood and adult malignancies.

Haber and her collaborators have also identified the role of ATP-binding cassette transporter genes (ABC transporters) in neuroblastoma biology, demonstrating that their expression predicts for poor clinical outcome in neuroblastoma [14] but, unexpectedly, this phenomenon was not due to the ABC proteins’ role in drug transport, but through an independent pathway that influences fundamental aspects of tumour biology. A further study on ovarian cancer and ABCA1 [15] has extended the discovery to common adult cancers.

Service to the scientific community

Haber is[ when? ] a long-term member of the International Neuroblastoma Risk Group Committee, which makes recommendations regarding standardised protocols and best practice for identifying/utilising prognostic indicators for neuroblastoma treatment risk assessment. [16]

From 2006 to 2014, Haber has served on the steering committee of the Advances in Neuroblastoma Research Association (ANRA), the peak international body for neuroblastoma research [17] and was president of this organisation from 2010 to 2012.

In 2011, Haber also played a key role in establishment of the Kids Cancer Alliance and currently serves on this organization's executive management committee. [18]

Haber is convenor of the 2016 Advances in Neuroblastoma Research conference in Cairns, one of the largest specialist childhood cancer conferences internationally. [19]

Recognition and awards

Related Research Articles

<span class="mw-page-title-main">ABC transporter</span> Gene family

The ABC transporters, ATP synthase (ATP)-binding cassette transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC transporters belong to translocases.

<span class="mw-page-title-main">P-glycoprotein</span> Mammalian protein found in Homo sapiens

P-glycoprotein 1 also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.

<span class="mw-page-title-main">Neuroblastoma</span> Medical condition

Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin.

<span class="mw-page-title-main">Efflux pump</span> Protein complexes that move compounds, generally toxic, out of bacterial cells

An efflux pump is an active transporter in cells that moves out unwanted material. Efflux pumps are an important component in bacteria in their ability to remove antibiotics. The efflux could also be the movement of heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that encode efflux pumps. Efflux pumps actively move substances out of a microorganism, in a process known as active efflux, which is a vital part of xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.

Geoffrey Chang is a professor at the University of California, San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences and Department of Pharmacology, School of Medicine. His laboratory focuses on the structural biology of integral membrane proteins, particularly exploring X-ray crystallography techniques for solving the tertiary structures of membrane proteins that are notoriously resistant to crystallization. The laboratory has specialized in structures of multidrug resistance transporter proteins in bacteria. In 2001, while a faculty member of The Scripps Research Institute, Chang was awarded a Beckman Young Investigators Award, designed to support researchers early in their academic careers, for his work on the structural biology of multidrug resistance. Chang announced a move from Scripps to neighboring UC San Diego in 2012.

<span class="mw-page-title-main">ABCC4</span> Protein-coding gene in the species Homo sapiens

ATP-binding cassette sub-family C member 4 (ABCC4), also known as the multidrug resistance-associated protein 4 (MRP4) or multi-specific organic anion transporter B (MOAT-B), is a protein that in humans is encoded by the ABCC4 gene.

<span class="mw-page-title-main">ABCG2</span> Protein-coding gene in the species Homo sapiens

ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ABCG2 gene. ABCG2 has also been designated as CDw338. ABCG2 is a translocation protein used to actively pump drugs and other compounds against their concentration gradient using the bonding and hydrolysis of ATP as the energy source.

<span class="mw-page-title-main">ABCC1</span> Protein-coding gene in the species Homo sapiens

Multidrug resistance-associated protein 1 (MRP1) is a protein that in humans is encoded by the ABCC1 gene.

<span class="mw-page-title-main">Multidrug resistance-associated protein 2</span> Protein-coding gene in the species Homo sapiens

Multidrug resistance-associated protein 2 (MRP2) also called canalicular multispecific organic anion transporter 1 (cMOAT) or ATP-binding cassette sub-family C member 2 (ABCC2) is a protein that in humans is encoded by the ABCC2 gene.

<span class="mw-page-title-main">ABCC3</span> Protein-coding gene in the species Homo sapiens

Canalicular multispecific organic anion transporter 2 is a protein that in humans is encoded by the ABCC3 gene.

<span class="mw-page-title-main">ABCC5</span> Protein-coding gene in the species Homo sapiens

Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ABCC5 gene.

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<span class="mw-page-title-main">Apatinib</span> Chemical compound

Apatinib, also known as rivoceranib, is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis in cancer cells; specifically, apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. This agent also mildly inhibits c-Kit and c-SRC tyrosine kinases.

The Lowy Cancer Research Centre is a facility at The University of New South Wales. It is Australia's first facility bringing together researchers in childhood and adult cancers, and one of the country's largest cancer research facilities, housing up to 400 researchers. The centre, named for businessman Frank Lowy, who donated $10 million towards the project, was officially opened on 28 May 2010. It is home to researchers from the UNSW Faculty of Medicine and Children's Cancer Institute Australia. The inaugural director is Professor Philip Hogg, winner of the Cancer Institute NSW Premier's Award for Outstanding Cancer Research in 2009.

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<span class="mw-page-title-main">Children's Cancer Institute</span>

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<span class="mw-page-title-main">June Biedler</span> American scientist

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References

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  10. Stewart, Bernard W.; White, Les; Davey, Ross A.; Bell, David R.; Kavallaris, Maria; Norris, Murray D.; Haber, Michelle (October 1989). "Atypical Multidrug Resistance in a Therapy-induced Drug-resistant Human Leukemia Cell Line (LALW-2): Resistance to Vinca Alkaloids Independent of P-Glycoprotein". Cancer Research. 49 (19): 5281–5287. PMID   2569932.
  11. Bordow, S. B.; Haber, M.; Madafiglio, J.; Cheung, B.; Marshall, G. M.; Norris, M. D. (1994). "Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma". Cancer Research. 54 (19): 5036–40. PMID   7923112.
  12. Norris, Murray D.; Bordow, Sharon B.; Marshall, Glenn M.; Haber, Paul S.; Cohn, Susan L.; Haber, Michelle (1996). "Expression of the Gene for Multidrug-Resistance–Associated Protein and Outcome in Patients with Neuroblastoma". New England Journal of Medicine. 334 (4): 231–238. doi: 10.1056/nejm199601253340405 . PMID   8532000.
  13. Haber, Michelle; Smith, Janice; Bordow, Sharon B.; Flemming, Claudia; Cohn, Susan L.; London, Wendy B.; Marshall, Glenn M.; Norris, Murray D. (2006). "Association of High-LevelMRP1Expression with Poor Clinical Outcome in a Large Prospective Study of Primary Neuroblastoma". Journal of Clinical Oncology. 24 (10): 1546–1553. doi:10.1200/JCO.2005.01.6196. PMID   16575006.
  14. Henderson, M. J.; Haber, M.; Porro, A.; et al. (2011). "ABCC multi drug transporters in childhood neuroblastoma: clinical and biological effects independent of cytotoxic drug efflux". Journal of the National Cancer Institute. 103 (16): 1236–51. doi:10.1093/jnci/djr256. PMC   3156802 . PMID   21799180.
  15. Hedditch, E. L.; et al. (2014). "ABCA transporter gene expression is associated with poor outcome in epithelial ovarian cancer". Journal of the National Cancer Institute. 106 (7): dju149. doi:10.1093/jnci/dju149. PMC   4110473 . PMID   24957074.
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