大象传媒

EMAIL: hdohlman@med.unc.edu

PERSONAL WEBSITE: /pharm/dohlmanlab/

PUBLICATIONS: Publications Link

The lab鈥檚 research is centered on G proteins, RGS proteins, and G protein-coupled receptors (GPCRs). Interest in these began, as a graduate student with Nobel Laureate Robert Lefkowitz, with the cloning and sequencing of the first neurotransmitter GPCR (Dixon et al. Nature 1986). GPCRs are the target of two thirds of all hormones and neurotransmitters, as well as a third of all pharmaceuticals.

GPCRs are conserved in evolution and are even found in the simplest eukaryotes. The lab has long been conducting large-scale genomic and proteomic analysis in yeast to identify mutants with altered signaling and desensitization properties. Work in yeast led to the identification and characterization of the first RGS proteins, which inactivate G proteins by accelerating their GTPase activity. Thus, GPCRs and RGS proteins have opposing actions, activating and inactivating G proteins, respectively.

In addition to RGS proteins, the lab identified enzymes that regulate G proteins through phosphorylation and dephosphorylation, as well as ubiquitination and deubiquitination. The lab pioneered the use of mass spectrometry to map sites of ubiquitination and demonstrated endomembrane signaling by G proteins.

In recent years the lab has been investigating G protein mutants linked to human disease, most notably uveal melanoma (Gq) and developmental and epileptic encephalopathy (Go), also known as GNAO1 disorder. These variant proteins are characterized at the molecular and cellular level, and with goal of developing novel therapeutics.