LAB MEMBERS

Morris Manolson
Principal Investigator, Lab Co-Ordinator

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Inflammatory arthritis not only causes painful swelling of affected joints, but also results in the loss of bone material around the arthritic joints. The pathological bone loss associated with arthritis results in increased bone fractures, deformation and collapse of joint surfaces, and difficulties in replacing the arthritic joints with implants and prostheses. We now know that the cells responsible for this bone loss (osteoclasts) resorb bone by pumping acid directly onto the bone surface; the secreted acid literally dissolving the bone surface away. In healthy bone, a percentage of the skeleton is continually dissolved away and remade (~15% of an adult's skeleton/year) in order to repair micro-fractures in the bone that occur daily with every moderate bump to one's skeleton. In inflammatory arthritis, this normal process of bone resorption becomes pathologically accelerated and results in an overall loss of bone around the arthritic joints.

My past work has been to advance our understanding of exactly how the osteoclast acid pumps (V-ATPases) pump the acid onto the bone. With my knowledge of the osteoclast acid pump, I am now focused on trying to develop therapeutic reagents that will specifically stop the acid pumps in order to prevent the accelerated bone loss associated with inflammatory types of arthritis, such as rheumatoid arthritis, psoriatic arthritis, reactive arthritis, juvenile rheumatoid arthritis and lupus.

Recent Publications

Ochotny NM, Van Vliet A, Chan N, Yao Y, Morel M, Kartner N, von Schroeder HP, Heersche JN, Manolson MF. Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity. J Biol Chem. 2006 download

Voronov I, Heersche JN, Casper RF, Tenenbaum HC, Manolson MF. Inhibition of osteoclast differentiation by polycyclic aryl hydrocarbons is dependent on cell density and RANKL concentration. Biochem Pharmacol. 2005 Jul 15;70(2):300-7. download

Shorey S, Heersche JN, Manolson MF. The relative contribution of cysteine proteinases and matrix metalloproteinases to the resorption process in osteoclasts derived from long bone and scapula. Bone. 2004 Oct;35(4):909-17. download