OR

Browse By

NHMRC Career Development Fellowship (CDF Level 2): Manipulation of haematopoietic stem cell niches to improve therapeutic outcomes (2013–2015)

Abstract:
This application is based on several strengths. First is my discovery of bone marrow (BM) factors that naturally regulate stem cells in vivo, including proteases, their inhibitors, macrophages, hypoxia, perfusion and more recently selectins. Second is my discovery of novel methodologies to investigate how niches alter cell behaviour in vivo. Most of this application is based on my discovery that E-selectin expressed at the BM vascular niche regulates HSC which are more quiescent & chemoresistant when E-selectin is absent/blocked. In the next 5 years I intend to pursue clinical applications by working with my industry partner to develop my existing IP (2 patents on use) plus identify the stem cell receptors involved, building on the glycobiology, drug design and commercialisation expertise of John Magnani, Vice President & founder of GlycoMimetics (MA, USA) who design & produces small molecule antagonists to develop my patents. In addition, I find normal & leukaemic myeloid progenitors proliferate faster in E-selectin KO mice leading to accelerated Acute Myeloid Leukaemia disease progression. I now plan to explore the basic biology & clinical applications of this discovery with the aim of ejecting leukaemia cells from protective niches to render them more susceptible to chemotherapy. Research plan for next 5 years During my placement with my industry partner (my IP is covered by 2 patents). 1) Develop antagonists to enhance HSC mobilisation & accelerate neutrophil recovery post-chemotherapy 2) Identify receptors involved in regulating HSC quiescence, self-renewal & chemo-protection My independent research in Australia 1) Identify factors that lodge leukaemia cells in protective (chemoresistant) BM niches with a view to improved treatment strategies. 2) Characterise other novel niche factors I have recently discovered, to ultimately improve therapeutic outcomes for patients, to enhance HSC transplantation success & to better treat leukaemia.
Grant type:
NHMRC Career Development Fellowship
Researchers:

  • Dr Ingrid Winkler

    Honorary Associate Professor
    Mater Research Institute-UQ
    Faculty of Medicine
Funded by:
National Health and Medical Research Council