The genetic and cellular control of lymphangiogenesis in health and disease (2015–2018)

Abstract:
The lymphatic vessel network is required for tissue fluid drainage and maintenance of fluid homeostasis. In both normal development and pathological conditions, lymphatic vessels form via lymphangiogenesis - the growth of lymphatic vessels from pre-existing vessels. This process is amenable to therapeutic intervention during metastasis because tumours induce lymphangiogenesis to spread to lymph nodes and on to distant sites. In the Hogan lab at IMB, I supervise a program of biomedical research that uses genetic screening in zebrafish to discover new genes and mechanisms that regulate lymphangiogenesis. We rapidly translate our fundamental mechanistic findings to mammalian models of development and disease. By understanding the molecular control of lymphangiogenesis, we can uncover the genetic aetiology of inherited vascular disorders and expand therapeutic avenues in lymphatic metastasis. In the first four years of my independent research group, my team has characterized prominent new molecular mechanisms in vascular development and disease published in high-impact journals. This career development fellowship will support my research program at the crucial early mid-career stage. The research proposal investigates major new genes and pathways that my team and I have discovered to be indispensible in new vessel formation. We will use cutting-edge genetic, cellular and biochemical approaches in vivo to delineate the molecular mechanisms at play in these pathways. In addition, we take innovative new systems-biology resolution approaches aiming to identify all major molecular pathways regulating our process of interest. Outcomes include the delineation of novel mechanisms of development and disease with potential for rapid translation to understanding vascular disorders and the metastatic spread of cancer.
Grant type:
NHMRC Career Development Fellowship
Funded by:
National Health and Medical Research Council