DECADES OF RESEARCH IN BONE CELL BIOLOGY, REGULATION OF OSTEOBLAST AND OSTEOCLAST DIFFERENTIATION

RESEARCH CAREER PROFILE
Filmed in Melbourne, Australia | May 2025

With
Thomas John Martin “Jack”,
Emeritus Professor of Medicine
University of Melbourne &
John Holt Fellow and Former Director,
St Vincent’s Institute of Medical Research
Melbourne, Australia

Emeritus Professor Jack Martin’s research began a discovery cascade that led to the identification of a new protein and the development of a novel and effective drug therapy that is now used worldwide to treat osteoporosis, cancer and other diseases.

Bones are essential for the overall structure and function of the human body, impacting everything from movement and protection to blood cell production, endocrine regulation and mineral storage.

Bone is made by the combined action of cells called osteoblasts (bone forming cells) and osteoclasts (cells that remove bone). To understand anything about bone it is important to find out what makes these two cell types do what they do.

In the 1970s, not a lot was known about bone. Professor Martin wanted to make a bone tumour in the laboratory that would respond to the newly discovered hormone, calcitonin. This was despite the fact that no-one had previously done this.

Professor Martin proposed that PTH and prostaglandins acted first on osteoblasts, and that osteoblasts responded by producing something that then caused osteoclasts to resorb bone.

Professor Martin’s ‘idiotic rationale’ and his presentation at the 1979 London meeting began a chain of events, stimulating research which was to continue for two decades, and resulting in the eventual discovery of RANK Ligand (RANKL), an osteoblast product that is essential for osteoclast formation and activity. An antibody against RANKL is now the most used drug in the treatment of osteoporosis.

Professor Martin’s work had a significant impact on the treatment of osteoporosis and the inhibition of cancer-caused bone loss – changing the way people see bone, and saving thousands of lives.

Professor Martin’s research for decades has been in bone cell biology, regulation of osteoblast and osteoclast differentiation and function by hormones and’ intercellular communication by cytokines. He purified and cloned PTHrP, established its role in hypercalcemia of cancer and its paracrine role in many tissues. He identified PTHrP as a cancer cell product contributing to the mechanisms by which cancer cells establish and grow in bone, and followed this with further basic and clinical studies.

He was Professor of Chemical  Pathology at the University of Sheffield (UK) from 1974 until 1977,  then Professor and Chairman of the University of Melbourne  Department of Medicine  until 1999.  He was Director of St Vincent’s Institute of Medical  Research from 1988 – 2002.

He has been a major contributor for 25 years to the study of mechanisms of skeletal metastases. A Fellow of the Royal Society and of the Australian Academy of Science,  he has been  President of the International Bone and Mineral Society and Vice President of the International Cancer and Bone Society.  Among awards were the Dale Medal in 1992 (UK),  the Chemofux Research Prize in 1988 (Vienna), the William F Neuman Award in 1994 (USA), The Pieter Gaillard Award in 2003, the Ramaciotti  Award in 2004, and the Gideon Rodan Award for Excellence in Mentorship, 2007.  He has published more than 500 scientific articles, 220 reviews and chapters, and edited 6 books.

Source: Adapted from supplied material