Scholar Profile

Garabed G. Sahagian

Associate Professor of Molecular Physiology and Pharmacology
Department of Physiology
Tufts University
136 Harrison Avenue
Boston, MA 02111
Voice: 617-636-6748
Fax: 617-636-0445
Personal Homepage
1986 Searle Scholar

Research Interests

Lysosome Biogenesis and Targeting of Proteins to Lysosomes

Interests of the lab are focused on the cellular processes related to intracellular trafficking of cathepsins and other lysosomal enzymes. These proteins are generally targeted to lysosomes by the well characterized phosphomannosyl recognition system. A key step in lysosomal targeting is selective phosphorylation which occurs on asparagine-linked oligosaccharides of the proteins as they enter and traverse the Golgi Apparatus. Recent work from the lab has suggested that a common lysine-based structure shared by cathepsins and other lysosomal proteins is responsible for the selectivity of the phosphorylation process.

We have been particularly interested in extralysosomal functions of lysosomal proteins. Over the past several years studies from this lab and others have revealed that certain lysosomal proteins, particularly the cathepsins, are subject to regulation at the levels of transcription and trafficking. Cathepsins diverted to the extracellular space in response to signals generated by hormones, growth factors and oncogenic transformation play important roles in a number of normal and pathological processes including tumor metastasis, bone resorption, spermatogenesis and embryo emplantation. How is intracellular trafficking of these proteins regulated and how do cathepsins and other lysosomal enzymes function in extralysosomal environments? These are questions that are currently being addressed.