Faculty
Hematology Division
Alphabetical list (active faculty):   
Philip W. Majerus

Philip W. Majerus, MD

July 10, 1936 - June 8, 2016

Professor (1966-2014)

Department of Medicine

Hematology Division

Department of Biochemistry & Molecular Biophysics

Research

Our laboratory is interested in defining the mechanisms by which cells respond to extracellular signals both to evoke intracellular responses and to modify the extracellular environment with specific reference to cells of blood and blood vessel walls. The laboratory utilizes techniques of biochemistry and molecular biology to study intracellular signaling reactions based on the inositol phosphate signaling pathway.

We have defined the pathways and functions involved in the phosphatidylinositol messenger-generating system. The phosphoinositides are minor phospholipids that undergo accelerated breakdown in response to extracellular agonists, such as small molecule effectors, peptide hormones and growth factors. A host of second-messenger molecules are produced, including derivatives of arachidonic acid, diacylglycerol and many inositol phosphates and phospholipids. We have recently discovered several new enzymes that lead to the synthesis of inositol hexaphosphate (InsP6). We have cloned and expressed several of these enzymes. Stable transfectants are being used to define messenger functions for InsP6 that include mRNA export, NHEJ DNA repair, and TNF induced apoptosis. Several of the enzymes of this pathway have recently been shown to be mutated as the cause of human diseases. Mutations in an isozyme of inositol polyphosphate 5-phosphatase cause Lowe syndrome that results in mental retardation, renal tubular acidosis and eye abnormalities. Mutations in myotubularins cause myotonic myopathy and Charcot-Marie-Tooth disease.

 

Phosphoinositides

Phosphatidylinositol signaling reactions

From: Zhang X, Majerus PW
Phosphatidylinositol signalling reactions.
Semin Cell Dev Biol. 1998 Apr;9(2):153-60