Kathleen Boesze-Battaglia

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Associate Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
School of Dental Medicine
240 South 40th Street
Levy Building, 5th Floor, Room 515
Philadelphia PA 19104
Philadelphia, PA 19104
Office: 215-898-9167
Fax: 215-898-3695
Lab: 215-746-0022
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Description of Research Expertise

Tetraspanin membrane proteins encompass a functionally diverse group of proteins involved in cell adhesion, cell recognition and membrane fusion events. These proteins are characterized by a highly conserved extra-cellular domain, known as the EC-2 domain that is involeid in formation of disulfide linked oligomers and functionally diverse C-termini. We are interested in understanding the role of two retinal specific tetraspanins, peripherin-2, the product of the rds gene, and it’s non-glycosylated homologue rom-1, in the development and progression of degenerative diseases. A murine model of retinitis pigmentosa (RP) in which a 10 kb insertion of exogeneous DNA results in an rds null allele as well as a rom-1 knockout mouse suggest that although peripherin-2 and rom-1 cooperate to generate healthy photoreceptors, they are not functionally equivalent and rom-1 likely plays a subsidiary role. Peripherin-2 and rom-1 form both homo and hetero-tetramers with peripherin-2 shown to oligomerize further to form octamers. Our studies focus on the regulatory and functional role played by the C-terminus of peripherin-2 in the formation of photoreceptor cells and in the maintenance of cell stability through the organization of intra-membraneous sacs known as disks. The C-terminal domain is required in the formation of newly developing membrane evaginations destined to become disks as well as their alignment along the outer segment portion of the cell. Domains within this region are postulated to be necessary for protein and vesicle targeting, calcium dependent calmodulin binding, membrane fusion, and the regulation of this fusion through the binding of a newly identified protein, melanoregulin. Using a combination of pull-down, immuno-precipitation, proteomic, confocal and live cell imaging techniques and as well as solution NMR, we have begun to define the regulatory surface of peripehirn-2. An understanding of how this region aids in disk membrane monogenesis and in maintaining photoreceptor viability is essential for the development of viable therapeutic approaches to slow the progression of these degenerations.

A second series of studies is designed to address the role of cholesterol in photoreceptor function and dysfunction during degeneration. Using a combination of membrane micro-domain isolation techniques, fluorescence anisotropy studies and functional readouts we have shown that membrane cholesterol is heterogeneously distributed within disks as a function of age and spatial distribution. Moreover this distribution results in compromised GPCR function due to changes in the membrane micro-environment and membrane fusion process.

Lastly, in a newly developing project, we have expanded our interest in cholesterol to address the role of this lipid in mineralizing tissue. Mutations within various cholesterol biosynthetic enzymes results in chondrodysplasia puntacta; punctate calcification of cartilage, leading in its’ more severe forms to mental retardation and in milder forms to skeletal abnormities including craniofacial defects. Using a combination of RNA interference techniques, membrane lipid asymmetry measurements and confocal microscopy we have focused our effort on understanding how enzymes involved in the maintenance of lipid asymmetry when devoid of a cholesterol- rich membrane environment begin to dysfunction leading to alterations in the formation of the core mineralizing component, the matrix vesicle. Through a series of collaborations we are utilizing AFM and primary cell culture models to understand how depletion of cell membrane cholesterol alters mineral formation and deposition.

Selected Publications

Damek-Poprawa, M., E. Golub, L. Otis, G. Harrison, C. Phillips and K. Boesze-Battaglia : Chondrocytes utilize a cholesterol dependent lipid translocator to externalize phosphatidylserine. Biochemistry 45: 3325-3336, 2006.

Boesze-Battaglia, K., D. Besack, T. McKay, A. Zekavat, L. Otis, K. Jordan-Sciutto and B.J. Shenker : Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin. Cellular Microbiology 8: 823-36, 2006.

Damek-Poprawa, M., J. Krouse, C. Gretzula and K. Boesze-Battaglia: A novel tetraspanin fusion protein, peripherin-2, requires a region upstream of the fusion domain for activity. J. Biol. Chem 280: 9217-24, 2005.

Boesze-Battaglia, K and A.F.X. Goldberg : Photoreceptor renewal: a role for peripherin/RDS. International Reviews in Cytology 217: 183-225, 2002.

Albert, A. and K. Boesze-Battaglia : The role of cholesterol in rod outer segment membranes. Progress in Lipid Research 44: 99-124, 2005.

Boesze-Battaglia, K., J. Dispoto and M.A. Kahoe: Association of a photoreceptor specific tetraspanin protein, ROM-1 with triton X-100 resistant membrane rafts from rod outer segment disk membranes. J. Biol. Chem 277: 41843-41849, 2002.

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Last updated: 05/20/2014
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