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Research Interests:

Age-related disease is a major public health problem. As global population demographics shifts towards a relatively older population, these diseases will become a catastrophic burden on both health care resources and on human well being. Our lab is interested in Alzheimer’s disease, and in the molecular pathways that it shares with other disorders. For example, the amyloid precursor protein (APP) is potentially involved in a variety of cellular processes, but is best known for its role as the source of a small peptide fragment known as the amyloid ß peptide (Aß). This peptide plays a major role in the development of Alzheimer’s disease in the brain. Aß and APP are also likely involved in the pathology of another age-related human degenerative disease – inclusion body myositis – in muscle. Recently, we have also begun to explore the connections between these processes and metabolic factors involved in type II diabetes, a condition known to confer significant risk for a variety of age-related conditions, including Alzheimer’s disease. We believe that these seemingly disparate diseases are connected not only at the level of shared molecular pathways, but are also connected at the level of transcriptional and translational regulation; our work is centered around understanding these factors. Our ultimate aim is to use the knowledge gained from these studies to refine model systems in which to develop novel therapeutic approaches. Recent studies include the use of NSAIDS (such as ibuprofen), immunotherapy, cholesterol lowering agents, and dietary modifications to modify the processes that we study, and that will hopefully one day lead to effective clinical treatments.

REPRESENTATIVE PUBLICATIONS

Head E, Moffat K, Das P, Sarsoza F, Poon WW, Landsberg G, Cotman CW, Murphy MP (2005). b-Amyloid deposition and tau hyperphosphorylation in aged cats with clinical signs of dementia. Neurobiol Aging, 26 (5): 749-763.

Murphy MP, Das P, Nyborg AC, Rochette MJ, Dodson M, Loosbrock NM,  Souder TM, McLendon DC, Merit SL, Piper SC, Jansen KR, Golde TE (2003). Nicastrin overexpression increases Ab Production. FASEB J, 17: 1138-1140 (published online April 8, 2003; 10.1096/fj.02-1050fje).

Piper SC, Amtul Z, Galiñanes-Garcia L, Howard VG, Ziani-Cherif C, McLendon C, Rochette MJ, Fauq A, Golde TE, Murphy MP (2003). Peptide-based, irreversible inhibitors of g-secretase activity. Biochem Biophys Res Comm, 305: 529-533.

Rochette MJ, Murphy MP. (2002) g-Secretase: Substrates and Inhibitors. Mol Neurobiol, 26(1): 81-95.

Murphy MP, Uljon SN, Golde TE, Wang R (2002). FAD-linked PS1 mutants alter the length of Ab-like fragments derived from bAPP transmembrane domain mutants. Biochim Biophys Acta, 1586: 199-209.

Sugarman MC, Yamasaki TR, Oddo S, Echegoyen JC, Murphy MP, Golde TE, Jannatipour M, Leissring MA, LaFerla FM (2002). Inclusion body myositis-like phenotype induced by transgenic overexpression of bAPP in skeletal muscle. Proc Natl Acad Sci USA, 99(9): 6334-6339.

Ni C-Y, Murphy MP, Golde TE, Carpenter G (2001). g-Secretase-dependent cleavage and nuclear localization of the ErbB4 receptor tyrosine kinase. Science, 294: 2179-2181.

Weggen S, Eriksen J, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH (2001). A subset of NSAIDs lower amyloidogenic Ab₄₂ independently of cyclooxygenase activity. Nature, 414: 212-216.