Brian E. Peerce, Ph.D., Associate Professor

  • Affiliations: Department of Neuroscience & Cell Biology
  • Route: 1069, 2.143I Medical Research Building (MRB)
  • Tel: (409) 772-3912
  • Fax: (409) 762-9382
  • bpeerce@utmb.edu

Brian E. Peerce, Ph.D.

Research Interests

                                • The laboratory conducts studies in 2 basic areas of research. The first is the study of the effect of inhibitors of intestinal absorption of dietary phosphorus on serum phosphate levels and the effect of reduced serum phosphate on the progression of chronic renal failure. The second area of research is the role of the proteasome/ubiquitin pathway in muscle wasting disorders and renal disease.

                                  Hyperphosphatemia (elevated plasma phosphate), and secondary hyperparathyroidism (elevated plasma PTH concentrations) are common, severe complications of chronic renal disease which contribute to the progression to end-stage renal disease. Decreasing serum PTH and serum phosphate have been associated with slowing and in some cases reversing the loss of renal function in clinical studies. We have developed an inhibitor of the intestinal brush border membrane Na+/phosphate cotransporter, NaPi II b (1-3), which reduces serum phosphate, and serum PTH, and slows the progressive loss of renal function (4).

                                  The second project is focused on myofibrillar protein degradation by the ubiquitin-proteasome pathway.  Muscle wasting is a serious complication of a variety of chronic diseases (diabetes, congestive heart failure, neurodegenerative diseases such as amyotrophic lateral sclerosis), acute trauma (burns and muscle injury), and disease treatments (glucocorticoid administration, cancer chemotherapy, and limb immobilization).  Loss of lean muscle mass in muscle wasting disorders is due to decreased myofibrillar protein synthesis and increased protein degradation.  Decreased protein synthesis appears to be related to 3 pathways – PKB/Akt, ERK1/2, and histone acetylation.  Skeletal muscle protein breakdown is related to increased UPP activity and increased polyubiquitination by 3 ubiquitin ligases (E3 , MURF, and MAF-box).  MAF-box (atrogin, muscle atrophy f-box protein) and MURF (muscle ring finger protein) are unique to skeletal muscle making them excellent therapeutic targets.  We have developed specific inhibitors of E3 and MAF-box.  These inhibitors are being used to identify MAF-box and E3 a target proteins in skeletal muscle.  The MAF-box inhibitor is also being used to examine the effect of MAF-box target proteins on myofibrillar protein synthesis.

Publications

                                • Peerce, B.E., and Clarke, R.D. A phosphorylated phloretin derivative. Synthesis and effect on intestinal Na+-dependent phosphate absorption. (2002) Am. J. Physiol. 283: G848-G855.

                                  Peerce, B.E., Fleming, R.Y.D., and Clarke, R.D. Inhibition of human intestinal brush border membrane vesicle Na+-dependent phosphate uptake by phosphophloretin derivatives. (2003) Biochem. Biophys. Res. Comm. 301: 8-12.

                                  Peerce, B.E., and Clarke, R.D. (2004) Phosphophloretin sensitivity of rabbit renal NaPi II a, and NaPi I a. Am. J. Physiol. 286: F955-F964.

                                  Peerce, B.E., Weaver, L., and Clarke, R.D. (2004) Effect of 2’-phosphophloretin on renal function in chronic renal failure rats. Am. J. Physiol. 287: F48-F56.

                                  Peerce, B.E., and Clarke, R.D. Renal cytoplasmic proteasome proteinase activities are altered  in chronic renal failure.  .  Arch. Biochem. Biophys. 444: 84; 2005