My research focus has been directed toward understanding the molecular basis of
transmembrane signaling by G protein-coupled receptors. This includes the study of their
structure using three-dimensional molecular graphics and modeling how the binding of
various drugs causes a shift in their conformational state. We are particularly
interested in the spontaneous activity exhibited by some receptors. In the case of D4
dopamine receptors we have characterized their conformation-dependent participation in
the process of phospholipid methylation, a unique and novel mechanism of signaling. A
cycle of D4 receptor-mediated phospholipid methylation requires resupply of a new methyl
group from the single carbon folate pool, thereby linking activity of the D4 receptor to
folate-dependent pathways of cellular metabolism. Different methylation states of the D4
receptor exhibit various degrees of spontaneous activity with regard to G protein
coupling. Deficits in D4 receptor-mediated phospholipid methylation may contribute to the
etiology of several neuropsychiatric disorders, including schizophrenia and depression.

Articles

PDF

Age-dependent decrease and alternative splicing of methionine synthase mRNA in human cerebral cortex and an accelerated decrease in autism (with Christina R. Muratore, Nathaniel W. Hodgson, Malav S. Trivedi, Hamid M. Abdolmaleky, Antonio M. Persico, Carla Lintas, and Suzanne De La Monte), Bouvé Faculty Publications (2013)

The folate and vitamin B12-dependent enzyme methionine synthase (MS) is highly sensitive to cellular oxidative...

 

PDF

Does inorganic mercury play a role in Alzheimer's Disease? A systematic review and an integrated molecular mechanism (with Joachim Mutter, Annika Curth, Johannes Naumann, and Harald Walach), Bouvé Faculty Publications (2010)

Mercury is one of the most toxic substances known to humans. It has been introduced...