I am a developmental cell biologist and molecular geneticist focusing on mechanisms controlling cell proliferation and modelling the development of cancer in the vinegar fly, Drosophila.
A major feature of tumour progression and cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy and hypertrophy suggesting that it may play a causal role in tumour formation and cardiac disease. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective at inhibiting the growth of some tumours and vascular smooth ....A major feature of tumour progression and cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy and hypertrophy suggesting that it may play a causal role in tumour formation and cardiac disease. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective at inhibiting the growth of some tumours and vascular smooth muscle. This study will examine the mechanisms that regulate ribosome synthesis. Specifically it focuses on a transcription factor termed UBF whose activity we think is critical for the regulation of the synthesis of the ribosomal RNA, the catalytic backbone of the ribosomes. Understanding the molecular mechanism(s) controlling UBF function will lead to a better comprehension of how cells modulate synthesis of functional ribosomes and how this process is deregulated during disease states associated with deregulated protein synthesis and growth such as cardiac hypertrophy and cancer.Read moreRead less
Programmed cell death (PCD), also known as apoptosis, plays a fundamental role in cell and tissue homeostasis and its misregulation is implicated in many human diseases. Many hormones control PCD but their mechanisms of action remain poorly understood. As hormones, in particular the steroid hormones, are directly linked to the pathogenesis of many forms of cancer, including breast, prostate and ovarian cancer, some of the most common malignancies afflicting the society, it is important to study ....Programmed cell death (PCD), also known as apoptosis, plays a fundamental role in cell and tissue homeostasis and its misregulation is implicated in many human diseases. Many hormones control PCD but their mechanisms of action remain poorly understood. As hormones, in particular the steroid hormones, are directly linked to the pathogenesis of many forms of cancer, including breast, prostate and ovarian cancer, some of the most common malignancies afflicting the society, it is important to study the mechanism of hormonal control of apoptosis in order to identify components of the regulatory apparatus. Identification of precise factors that regulate PCD will not only provide basic understanding of hormone-controlled PCD, but any novel factors involved in the control of cellular levels of death activators or death inhibitors are potential targets for anticancer drug development. This proposal is based on our ongoing studies, which combine the powerful biochemical and cellular approaches with the in vivo studies in vinegar fly (Drosophila) to address complex issues that are often difficult to pursue by the direct use of mammalian systems. We believe that the results from this study will provide novel insights into the mechanisms of hormone-regulated control of PCD and how these control mechanisms are disrupted under pathological conditions.Read moreRead less