Peter S N Rowe, B.Sc (Hons), Ph.D.
Nephrology - Professor
Kidney Institute - Faculty
University of Kansas Cancer Center Drug Discovery, Delivery & Experimental Therapeutics - Full Member
Kidney Institute, Internal Medicine
Ph.D., University College London; England, 1981
Medical Research Council (MRC) Senior Fellowship (United Kingdom); University College London (England), 1996-2001
Publications: Click here
The research in this group is aimed at increasing our understanding of the molecular bone-renal mechanisms that maintain a healthy mineralized skeleton and dentition. Since this dynamic-process is disturbed dramatically in many tumor-acquired and inherited diseases we are also studying these diseases in the hope that our findings will help to improve clinical treatment. In collaboration with an international consortium (HYP-consortium) we successfully identified the primary gene defect in an inherited bone-renal disease, X-linked hypophosphatemic rickets (HYP). This disease is characterized by severe under-mineralization of the skeleton and marked changes in renal-phosphate handling and vitamin D metabolism. We named this novel gene PHEX (acronym: phosphate regulating gene with homologies to endopeptidases on the X-chromosome). This discovery has stimulated new research and provided new reagents aimed at unraveling the molecular pathways downstream of the primary PHEX gene-product defect. More recently, we were the first to characterize and clone a completely novel bone-matrix protein (MEPE) from patients with tumor-induced osteomalacia. Also, we have demonstrated biological activity of this new MEPE protein and confirmed a direct interaction with PHEX. Our research indicates that a small acidic, protease-resistant MEPE-peptide that we named ASARM-peptide, could potentially be the first ‘biological bisphosphonate’ described. This peptide occurs in MEPE and some related family proteins (SIBLINGs) and the acronym ASARM stands for acidic-serine-aspartate-rich-MEPE-associated motif. The biological and physicochemical properties of the ASARM-peptide are remarkably similar to etidronate, a bisphosphonate. The ASARM-peptide (like etidronate) inhibits mineralization in-vivo and in-vitro and impacts on renal phosphate handling. Our research confirms ASARM-peptides play a major role in regulating mineralization, bone resorption and renal calcification.
Overview: Molecular Osteo-renal Research
To preserve a healthy skeleton and dentition a complex and exquisitely regulated process has evolved that involves complex interactions between the kidney, liver, skin, parathyroid-glands and brain. Growth factors, hormones, extracellular-matrix proteins, matrix-proteases and receptors mediate these dynamic interactions via a bewildering number of bone-cells (osteoblasts, odontoblasts, osteoclasts and osteocytes for example). These cells are interwoven by an intricate tapestry of molecules (collagen, proteoglycans), and cemented by a mineral-matrix (hydroxyapatite), consisting mainly of calcium and phosphate. The net result is an extraordinarily complex molecular and anatomical structure that is in constant flux with the external environment. In order to maintain the integrity of the skeleton, the concentrations of phosphate and calcium in plasma are monitored by sophisticated molecular sensing mechanisms. These mechanisms modulate bone mineralization, bone formation/resorption, intestinal calcium/phosphate uptake and renal mineral transport. Genetic factors, environmental circumstance and disease (cancer for example) impact on this finely tuned balance in major and unexpected ways.
Our research aims to generate biological compounds that will have potential for the therapeutic treatment of tumor and familial diseases that result in bone-mineral loss and hypophosphatemic and hyperphosphatemic conditions. These diseases include tumor induced osteomalacia (OHO, TIO), X-linked and autosomal forms of hypophosphatemic rickets (HYP, ADHR), renal osteodystrophy, end stage renal failure, renal toxicity, renal-transplantation, ectopic calcification (vascular and renal), periodontal disease and osteoporosis.
Rowe Laboratory website