Kathleen Berkner Ph.D.

Staff

  • Department of Molecular Cardiology
  • Lerner Research Institute / NB50
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • berknek@ccf.org
  • (216) 445-9760
  • (216) 444-9263

Carboxylation of vitamin K-dependent (VKD) proteins renders them active in a broad range of physiologies. This modification generates a calcium-binding module in VKD proteins that targets them to cell surfaces or extracellular matrix where they function in hemostasis, calcium homoeostasis, apoptosis, cell proliferation, and signal transduction. A goal in our laboratory is to define the complex process by which VKD proteins become carboxylated. One focus is on the VKD carboxylase, which uses reduced vitamin K to carboxylate Glus in VKD proteins. We are using biochemical analysis, cell-based assays and animal models to define carboxylase mechanism, and questions include whether the carboxylase can distinguish between various VKD proteins and how carboxylase mutations lead to different disease states. Another focus is on the reductase VKOR that provides the reduced vitamin K to the carboxylase. VKOR is the target of the anticoagulant warfarin, a fairly nonspecific drug, and studies on VKOR are important for developing superior anticoagulants. We showed that VKOR activity limits carboxylation, and one direction is to determine why VKOR is limiting. We are also interested in the role of the VKD carboxylase in nonmammalian organisms. We showed that the bacterium Leptospira interrogans has acquired the carboxylase by horizontal transfer and has adapted it for an unknown function. This pathogen causes Leptospirosis, and our goal is to determine the function of the bacterial carboxylase ortholog and how it contributes to the pathogenesis of this disease.

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  • Kevin Hallgren
  • Research Technologist
  • Location:NB5-125
  • Phone:(216) 445-9764
  • Fax:(216) 444-9263
  • hallgrk@ccf.org
  • Mark Rishavy Ph.D.
  • Project Staff
  • Location:NB5-125
  • Phone:(216) 445-9764
  • Fax:(216) 444-9764
  • rishavm@ccf.org
  • Savita Singh
  • Graduate Student
  • Location:NB5-128
  • Phone:(216) 445-9764
  • singhs5@ccf.org
  • Lee Adrienne Wilson
  • Research Technician
  • Location:NB5-125
  • Phone:(216) 445-9764
  • carlsel@ccf.org

Rishavy MA, Hallgren KW, Yakubenko AV, Shtofman RL, Runge KW, Berkner KL. Biochemistry (2006) 45(44):13239-48. Darghouth D, Hallgren KW, Shtofman RL, Mrad A, Gharbi Y, Maherzi A, Kastally R, LeRicousse S, Berkner KL, Rosa JP. Blood (2006) 108(6):1925-31. Hallgren KW, Qian W, Yakubenko AV, Runge KW, Berkner KL. Biochemistry (2006) 45(17):5587-98. Berkner KL. Annu Rev Nutr. (2005) 25:127-49.

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