Last Updated: 7/2/2007

Clinical Interests
not applicable

Research Interests
Our primary focus is the regulation of G proteins and downstream MAP kinases. G protein-coupled receptors detect neurotransmitters, hormones, odors, taste and light. Genetic defects in G protein signaling pathways can cause a variety of developmental and metabolic disorders, including cancer, obesity, narcolepsy, drug addiction, and resistance to HIV infection.
G proteins and MAP kinases are highly conserved in evolution, and are even found in the simplest eukaryotes such as the yeast Saccharomyces cerevisiae. We have been conducting large-scale genomic and proteomic screens in yeast to identify mutants with altered signaling and desensitization properties. Such mutants have then been characterized biochemically, both in yeast and in animal cells (using homologous components). This approach led to the identification in yeast of a new family of desensitization factors called RGS proteins (Regulator of G protein signaling), which promote G protein inactivation by accelerating GTPase activity.
More recently we have investigated how post-translational modifications of known signaling proteins (e.g. ubiquitination, myristoylation) can lead to accelerated degradation or redistribution within the cell. New efforts (with Professor Tim Elston) are focused on obtaining quantitative measurements and computational models of the G protein and MAP kinase signaling cascade, with the eventual goal of devising predictive models of signal transduction in more complex systems.

Publications
1. Hao, N., Behar, M., Parnell, S. C., Torres, M. P., Borchers, C. H., Elston, T. C., and Dohlman, H. G., A systems-biology analysis of feedback inhibition in the Sho1 osmotic stress-response pathway. Curr. Biol. 17:659-67, 2007.

2. Hao, N., Behar, M., Elston, T. C., and Dohlman, H. G., Systems biology analysis of G protein and MAP kinase signaling in yeast. Oncogene 26:3254-66, 2007.

3. Slessareva, J., and Dohlman, H. G., G protein signaling in yeast: new components, new connections, new compartments. Science 4:1412-3, 2006.

4. Ballon, D. R., Flanary, P. L., Gladue, D. P., Konopka, J. B., Dohlman, H. G., and Thorner, J., DEP-domain-mediated regulation of GPCR signaling responses. Cell 126, 1079-1093, 2006

5. Slessareva, J. E., Routt S. M., Temple, B., Bankaitis, V. A., and Dohlman, H. G., Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome. Cell 126:191-203, 2006.

E-mail: hdohlman@med.unc.edu
Telephone: 919-843-6894
FAX: 919-966-2852
Address: Department of Biochemistry and Biophysics, 405 Mary Ellen Jones Building, Campus Box 7260 Chapel Hill, NC 27599-7260
URL: www.med.unc.edu/~hdohlman/DohlmanLab.html

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