Crispin Dass

Prof. Crispin R Dass,
School of Pharmacy and Biomedical Sciences,
Faculty of Health Sciences.,
Curtin University, Australia
Tel: 08 9266 1489
Email: Crispin.Dass@curtin.edu.au

 

CURRICULUM VITAE

Professor Dass majored in Medical Biotechnology, with a first class Honours from Charles Sturt University, NSW. He then obtained a doctorate in the field of Biomedical Sciences, in the area of cancer therapy, at the same University. Prof. Dass has 25 years of basic and applied research in cancer, with skills such as in vivo (small animal) and cell culture testing experience and significant drug formulation and delivery skills. His PhD project, on targeted gene therapy for cancer, in the mid-90s, was one of the earliest applications of gene transfer in Australia. He is well-versed in medium-throughput screening of potential lead compounds for cancer drug R&D, and he has worked on bigpharma projects (Amgen, Novartis, Glaxo-Wellcome, Johnson & Johnson) in oncology and drug testing. Prof. Dass also has 24 years of experience using a wide range of molecular techniques including real-time PCR, western blotting, immunohistochemistry and molecular therapy. Prof. Dass has been at a lab leadership role for the past 11 years, all in the area of cancer drug discovery, delivery and development.

 

ABSTRACT

Pigment epithelium-derived factor (PEDF) possesses evolutionary-diversified roles that include the regulation of angiogenesis, neural stem cell survival and differentiation, antioxidant function in the eye, pro-differentiation in the bone, and growth inhibition in a variety of cancers. PEDF is downregulated in breast cancer patients.  Of note, PEDF has a high affinity binding site for collagen I, the major protein found in bone, as well as glycosaminoglycans (GAGs) such as heparin and hyaluronan, which play important roles in bone formation. We have demonstrated that PEDF downregulates MT1-MMP expression in a variety of cancer cells including the ER breast cancer cell line MDA-MB231. Osteoclasts play a dominant role in breast cancer metastases to bone. The human ER+ breast cancer cell line MCF-7 secretes RANKL, which promotes osteoclastogenesis and subsequent bone mineral resorption. RANKL and RANK are expressed by mammary epithelial cells under the control of sex hormones, and RANK and RANKL control the preferential metastasis of breast cancer cells to the bone. We demonstrated that PEDF downregulates osteoclast differentiation, survival and activity via upregulation of osteoprotegerin (OPG), a decoy for RANKL. More recently, we have shown that PEDF is able to induce bone regeneration. This now allows us to use this versatile protein in not only controlling primary tumour spreading to the bones, but also repairing the damage done at the bone lesion sites. Results of studies with two tumours, osteosarcoma and breast cancer, will be discussed.