Sanders-Brown Faculty

| A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z |

Michael P. Murphy, Ph.D.

Assistant Professor

Departmental Affiliation(s):

Molecular and Cellular Biochemistry

Research Focus:

Pathogenic mechanisms and treatment of age-related amyloid diseases

Research Synopsis: 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 β peptide (Aβ). This peptide plays a major role in the development of Alzheimer’s disease in the brain. Aβ 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.

In the lab:

Tina L Beckett (Research Analyst, Pr.)

Robin L Webb (Graduate Student)

Chris J Holler (Graduate Student)

Dana Niedowicz (Post-Doctoral Scholar)

                   

                       

 

 

 

 

 

 

 

Lab Mission:

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. Our lab studies the processes that generate Aß from APP, and the factors that regulate these at the cellular and molecular level. Our aim is to use the knowledge gained from these studies to refine model systems in which to develop novel therapeutic approaches that may one day lead to effective clinical treatments for both disorders. Recent studies include the use of widely available nonsteroidal anti-inflammatories (NSAIDs, such as ibuprofen), passive immunotherapy, and lowering of cholesterol using commonly prescribed drugs.

Recent Publications:

Studzinski CM, et. al. (2008) Effects of short term western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice. J Neurochem, in press.

Studzinski CM, et al. (2008) Induction of Ketosis May Improve Mitochondrial Function and Decrease Steady-State Amyloid-β Precursor Protein (APP) Levels in the Aged Dog. Brain Res, in press.

Galasko DR, Graff-Radford N, May S, Hendrix S, Cottrell BA, Sagi SA, Mather G, Laughlin M, Zavitz KH, Swabb E, Golde TE, Murphy MP, Koo EH. Safety, Tolerability, Pharmacokinetics, and Abeta Levels After Short-term Administration of R-flurbiprofen in Healthy Elderly Individuals. Alzheimer Dis Assoc Disord 21: 292-299, 2007.

Kukar T, Prescott S, Eriksen JL, Holloway V, Murphy MP, Koo EH, Golde TE, Nicolle MM. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice. BMC Neurosci 8: 54, 2007.

Liu Y, Guan H, Beckett TL, Juliano MA, Juliano L, Song ES, Chow KM, Murphy MP, Hersh LB. In vitro and in vivo degradation of Abeta peptide by peptidases coupled to erythrocytes. Peptides 28: 2348-2355, 2007.

Murphy MP, Beckett TL, Ding Q, Patel E, Markesbery WR, St Clair DK, LeVine H, 3rd, Keller JN. Abeta solubility and deposition during AD progression and in APPxPS-1 knock-in mice. Neurobiol Dis 27: 301-311, 2007.

Anantharam M, et. al. (2006). β-Amyloid mediated nitration of manganese superoxide dismutase: implications for oxidative stress in a APPNLh x PS1P264L double knock-in mouse model of Alzheimer’s disease. Am J Pathol, 168(5): 1608-18.