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Associate Professor of Biochemistry and Biophysics
Ph.D. University of Bath 1990

Dr. Pearce uses yeast and mouse models for the study of childrens neurodegenerative diseases.

Batten disease is one of the more common childhood neurodegenerative diseases. Children with this disease usually suffer visual failure, psychomotor deterioration, seizures and premature death. Although the underlying defect to this disease, a defective CLN3 gene, was first identified in 1995, very little progress has been made in understanding Cln3p function and how a defective Cln3p causes Batten disease. Individuals with Batten disease exhibit accumulation of lipopigments in the lysosome, predominantly the proteolipid, mitochondrial ATPase subunit c, leading people to believe that the turnover of this protein is somehow affected. Our lab has cloned the yeast homolog to Cln3p, designated Btn1p, and has established that this protein is not involved in the degradation of mitochondrial proteins. We have established that vaculolar/lysosomal pH regulation is altered in yeast strains lacking Btn1p. We are using the numerous genetic techniques available to a yeast molecular biologist to study the function of Btn1p, which can then be applied to understanding Batten disease.

We are also studying a mouse that lacks the mouse equivalent of CLN3, and are in the process of characterizing the degeneration specific to lacking this protein, utilizing a variety of histological and molecular biological techniques including microarray studies.

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Recent Publications

Osorio NS, Sampaio-Marques B, Chan CH, Oliveira P, Pearce DA, Sousa N, Rodrigues F (2009) Neurodevelopmental delay in the Cln3(triangle upex7/8) mouse model for Batten disease. Genes Brain Behav,

Seehafer SS, Pearce DA (2009) Spectral properties and mechanisms that underlie autofluorescent accumulations in Batten disease. Biochem Biophys Res Commun,

Benedict JW, Getty AL, Wishart TM, Gillingwater TH, Pearce DA (2009) Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2. J Neurosci Res,

Weimer JM, Benedict JW, Getty AL, Pontikis CC, Lim MJ, Cooper JD, Pearce DA (2009) Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis. Brain Res,

Chan CH, Ramirez-Montealegre D, Pearce DA (2009) Altered arginine metabolism in the central nervous system (CNS) of the Cln3-/- mouse model of juvenile Batten disease. Neuropathol Appl Neurobiol, 35:189-207

Chan CH, Mitchison HM, Pearce DA (2008) Transcript and in silico analysis of CLN3 in juvenile neuronal ceroid lipofuscinosis and associated mouse models. Hum Mol Genet, 17:3332-9

Kovacs AD, Pearce DA (2008) Attenuation of AMPA receptor activity improves motor skills in a mouse model of juvenile Batten disease. Exp Neurol, 209:288-91

Castaneda JA, Pearce DA (2008) Identification of alpha-fetoprotein as an autoantigen in juvenile Batten disease. Neurobiol Dis, 29:92-102

Fatemi SH, Reutiman TJ, Folsom TD, Huang H, Oishi K, Mori S, Smee DF, Pearce DA, Winter C, Sohr R, Juckel G (2008) Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res, 99:56-70

Castaneda JA, Lim MJ, Cooper JD, Pearce DA (2008) Immune system irregularities in lysosomal storage disorders. Acta Neuropathol, 115:159-74

Benedict JW, Sommers CA, Pearce DA (2007) Progressive oxidative damage in the central nervous system of a murine model for juvenile Batten disease. J Neurosci Res, 85:2882-91

Osorio NS, Carvalho A, Almeida AJ, Padilla-Lopez S, Leao C, Laranjinha J, Ludovico P, Pearce DA, Rodrigues F (2007) Nitric Oxide Signaling Is Disrupted in the Yeast Model for Batten Disease. Mol Biol Cell,

Vitiello SP, Wolfe DM, Pearce DA (2007) Absence of Btn1p in the yeast model for juvenile Batten disease may cause arginine to become toxic to yeast cells. Hum Mol Genet, 16:1007-16

Adams HR, Kwon J, Marshall FJ, de Blieck EA, Pearce DA, Mink JW (2007) Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies. J Child Neurol, 22:621-7

Zimmerman AW, Connors SL, Matteson KJ, Lee LC, Singer HS, Castaneda JA, Pearce DA (2007) Maternal antibrain antibodies in autism. Brain Behav Immun, 21:351-7

Osorio NS, Carvalho A, Almeida AJ, Padilla-Lopez S, Leao C, Laranjinha J, Ludovico P, Pearce DA, Rodrigues F (2007) Nitric oxide signaling is disrupted in the yeast model for Batten disease. Mol Biol Cell, 18:2755-67

Lim MJ, Alexander N, Benedict JW, Chattopadhyay S, Shemilt SJ, Guerin CJ, Cooper JD, Pearce DA (2007) IgG entry and deposition are components of the neuroimmune response in Batten disease. Neurobiol Dis, 25:239-251

Weimer JM, Benedict JW, Elshatory YM, Short DW, Ramirez-Montealegre D, Ryan DA, Alexander NA, Federoff HJ, Cooper JD, Pearce DA (2007) Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis. Brain Res, 1162:98-112

Ramirez-Montealegre D, Pearce DA (2007) Imaging of late infantile neuronal ceroid lipofuscinosis: a clinical rating scale. Neurology, 69:503-4

Brouxhon S, Kyrkanides S, O'Banion MK, Johnson R, Pearce DA, Centola GM, Miller JN, McGrath KH, Erdle B, Scott G, Schneider S, VanBuskirk J, Pentland AP (2007) Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2 dependent posttranslational mechanism. Cancer Res, 67:7654-64

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry
Ph.D. in Genetics
Ph.D. in Neuroscience

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: David_Pearce@urmc.rochester.edu

David Pearce
Center for Aging and Developmental Biology
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 645
Rochester, New York 14642

Office: Medical Center KMRB 1-9627
Telephone: (585) 273-1514; Fax: (585) 756-7665