PhD (Griffith University), Graduate Diploma of Clinical Biochemistry (Griffith University), Bachelor of Science (Griffith University)
Associate Professor Larisa Haupt is a Principal Research Fellow and the Neurogenesis and Stem Cell Group Leader within the Genomics Research Centre at IHBI. A/Prof Haupt has extensive research expertise in the extracellular matrix, stem cells, cell and molecular biology and human molecular genetics. Her research team has a particular interest in the role of the extracellular matrix, with a focus on the proteoglycans, in the regulation and dysregulation of cell behaviour including lineage specification and cancer.
A/Prof Haupt and her team utilise molecular and cell biological in two- and three-dimensional culture models as well as next generation sequencing platforms to unravel these complex mechanisms in humans. Models used for this work currently include: primary human mesenchymal stem cells (hMSC); human embryonic stem cell derived neural stem cells (hNSC H9 and ENStem-A); primary cortex derived normal human progenitor cells (nhNPC); human immortilised frontal cortex-derived cells (ReNcell CX); patient-derived Alzheimer’s Disease iPSC-NSCs (AD-iPSC-NSCs); human primary normal human mammary epithelial cells (HMECs); and human breast cancer (HBC) cell lines.
In the last 10 years, A/Prof Haupt has published 70 manuscripts, with a current H index of 24 and an i10-index of 48. In addition to this output, A/Prof Haupt has established a series of multi-disciplinary research collaborations across University, government and non-government sectors, both within Australia and Internationally. These collaborations include researchers working in the discipline areas of human molecular genetics, pathology, bone and stem cell biology, protein biochemistry, biomaterials and breast cancer research. A/Prof Haupt has successfully been awarded >$3,5M in grant funding with a current total grant funding income of $1.6M.
To date, work from A/Prof Haupt and her research team has to evidence supporting the emergence and understanding of the role of heparan sulfate proteoglycans (HSPGs) in mediating important cellular events including proliferation and differentiation in both normal and pathological conditions. Most recently, this has identified a role for HSPGs in human neural stem cells (hNSC) proliferation and lineage specification and a potential role for these important proteins in breast cancer tumorgenicity.
1999 – 2001 Postdoctoral Research Fellow, Thea D. Tlsty Lab, School of Medicine, Department of Pathology, University of California San Francisco.
Tissue obtained from women undergoing reduction mammaplasties, lumpectomy and mastectomy, along with autopsy material, was used for the isolation of human mammary cell populations (epithelial and stromal fibroblasts). Several strains from tumours and reduction mammaplasties were successfully propagated in vitro and characterised using flow cytometry, immunocytochemistry, two-dimensional in vitro cell culture, FISH and karyotypic analysis. In conjunction, paraffin embedded biopsy material was examined using immunohistochemistry and correlated to clinical data including estrogen receptor status, lymph node involvement, and clinical diagnosis. Human breast cancer (HBC) cell lines were also used in vitro to establish two- and three- dimensional culture conditions using Matrigel, vitronectin, collagen and fibroblasts and examined by conventional, phase-contrast and confocal microscopy. Data from this work demonstrated for the first time the genomic instability of primary human mammary epithelial cells and resulted in manuscripts published in Natureand the Journal of Mammary Gland Biology and Neoplasia.
2001 – 2002 Postdoctoral Research Fellow, Johannes B. Prins Lab, Department of Medicine, University of Queensland, Brisbane Australia
In order to elucidate mechanisms involved in human adipogenesis, primary human adipocytes differentiated in vitro and mature adipocytes isolated from both omental and subcutaneous depots were utilised. Both types of sample were used to examine gene expression by traditional RT-PCR, microarray analysis, Q-PCR and immunocytochemical analysis. In addition, fixed, paraffin embedded tissue was archived for use in immunohistochemistry and in situhybridisation. Experimental data was correlated to clinical data including BMI, insulin resistance, age and depot specificity. Data from this work contributed toward publication in Diabetes and Vascular Research and an oral presentation at the Australian Diabetes Society Annual Meeting.
2004 – 2008 Senior Postdoctoral Fellow, Victor Nurcombe/Simon Cool, Stem Cell and Tissue Repair Laboratory, A*STARInstitute of Molecular and Cell Biology, Singapore
Research projects focused on the Runx2/Heparan sulfate regulation of proliferation and differentiation of mesenchymal stem cells. Specific projects included the examination of the effects of GAG depletion on in vitroosteogenesis; examination of the Runx2/FGF axis and cell cycle parameters in proliferation versus differentiation; temporal and spatial PG distribution during embryogenesis; and the role of HS in bone development using an in vitromurine calvarial model. Data from this work has resulted in contributions toward manuscripts in Journal of Cellular Physiology, Stem Cells in Development, Journal of Cellular Biochemistry, Journal of Molecular Histology, Bone, and Biomacromolecules.
2010 – 2013 Program Leader Mesenchymal Stem Cell Research Program, Senior Research Fellow, Genomics Research Centre, Griffith University Gold Coast
2013 – present Group Leader, Neurogenesis and Stem Cells, Senior Research Fellow, Laboratory Manager, Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology
Human neural stem cells (hNSCs) and mesenchymal stem cells (hMSCs) are now routinely used in cell culture models, however the processes and the mechanisms that regulate these cells are still largely unknown. Despite hMSC neural lineage potential, the current lack of understanding of lineage regulation limits their use in the development of human neurogenesis models as well as our understanding of how numerous neurological and brain disorders occur. The identification of the biomarkers required for maintaining neural stem cells in their undifferentiated state as well as those needed to direct lineage differentiation is central to understanding neurogenesis. How these processes are regulated will help to further unravel the structural complexity of the human brain, and the role of associated biological and other factors in neurogenesis. These also have important ramifications for the successful integration of newly formed neurons into existing/remaining neural circuits.
The heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) are widely distributed in the body and the nervous system, primarily in the extracellular matrix. Multiple studies have identified a role for these proteins during normal development of the nervous system as well as in the maintenance of stem cell pools in the adult. What has yet to be elucidated is how these PGs contribute to the control of neural lineage regulation, proliferation and differentiation? As NSCs have the ability to generate neurons, astrocytes and oligodendrocytes, these cells provide a promising model for understanding the process of neurogenesis. In addition, MSCs have neural lineage potential and may contribute to the localised microenvironment to mediate stemness as well as lineage specification. The identification of the factors regulating these cellular processes will complement broader research disciplines that could be applied to all fields of research and may provide new strategies for their efficient implementation in therapeutic applications.