Professor, Biochemistry and Molecular Biology

Paul Sorgen, PhDPhone: 402-559-7557 (Office)
402-559-7566 (Lab)
Fax: 402-559-6650
Email: psorgen@unmc.edu

Education/Training:
Ph.D., University of Florida, 1999

Research: 

Research Opportunities in my Lab:
Post-Doctoral Positions, full time
Medical students, summer research
Undergraduate students, summer research

sorgen lab
Sorgen Lab Members: Kelly Stauch, Rosslyn Grosely, Sydney Zach, Cali Reiling, Gaelle Spagnol, Hanjun Li, Mona Al-mugotir, Jennifer Kopanic, and Paul Sorgen.

Connexins are integral membrane proteins that oligomerize to form intercellular gap junction channels. These channels provide diffusional intercellular exchange of ions and small molecules, allowing individual cell events to synchronize into the functional response of an entire organ. Gap junctions mediate vitally important processes such as impulse propagation, regulation of cell growth, and organ development. Moreover, mutations in a gap junction protein are linked to various inherited diseases, including nervous system disorders, deafness, cataracts, heart defects, and skin diseases. While there is considerable information regarding key interactions of connexins in the regulation of gap junction channels, the precise mechanisms that lead to channel closure have not been defined, nor have the critical accessory proteins involved been fully characterized. This information is pivotal if intercellular communication in normal and diseased states is to be fully understood. Our laboratory is focused on using molecular, biological, and biochemical techniques to help define the mechanism of gap junction channel closure by pH and phosphorylation.

Gap Junction model  Connexin model 

Model of a Gap Junction Channel. Gap junctions are formed by the apposition of connexons from adjacent cells, where each connexon is formed by six connexin proteins The channel location has been indicated by the yellow circle.

Model of a Connexin with Cellular Partners. Connexins are tetraspan transmembrane domain proteins with intracellular N- and C-termini. There are 21 different connexin genes in the human genome. The abbreviations are as follows: NT, N-terminus; CL, cytoplasmic loop; CT, C-terminus; E1 and E2, extracellular loops 1 and 2; 1-4, transmembrane segments 1-4.

Publications:

Kieken F, Spagnol G, Vivian S, Lau A, and Sorgen PL. (2010) NMR structure note: UBA domain of CIP75. J. Biomolecular NMR. 46(3):245-50.

Pfenniger A, Derouette JP, Verma V, Lin X, Foglia B, Coombs W, Roth I, Satta N, Dunoyer-Geindre S, Sorgen PL, Taffet S, Kwak BR, and Delmar M. (2010)The gap junction protein Cx37 interactions with eNOS in endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 30(4):827-34.

Kieken F*, Sharma M*, Jovic M, Panapakkam SS, Naslavsky N, Caplan S#, and Sorgen PL#. (2010) Acidic clusters regulate the selectivity of EHDS for specific NPF-containing proteins. 2nd submission to J. Biol. Chem. 285(12):8687-94.

Grosely R, Kieken F, and Sorgen PL. (2010) Optimizing the solution conditions to solve the structure of the Connexin43 carboxyl terminus attached to the 4th transmembrane domain in detergent micelles. Cell Communication and Adhesion. In Press.

Kieken, F., Jovic, M., Tonelli M., Naslavsky, N., Caplan, S., and Sorgen, P. (2009) Structural insight into the interaction of proteins containing NPF, DPF and GPF motifs with the C-terminal EH-domain of EHD1. Protein Science, 2009; 18(12):2471-9.

Bouvier D, Spagnol G, Chenavas S, Kieken F, Vitrac H, Brownell S, Kellezi A, Forge V, and Sorgen PL. (2009) Characterization of the structure and intermolecular interactions between the Connexin40 and Connexin43 carboxyl terminal and cytoplasmic loop domains. J. Biol. Chem. 284(49):34257-71.

Kieken, F., Mutsaers, N., Dolmatova, E., Virgil, K., Wit, A.L., Kellezi, A., Hirst-Jensen, B.J., Duffy, H.S., and Sorgen, P.L. (2009) Structural and molecular mechanisms of gap junction remodeling in epicardial border zone myocyctes following myocardial infarction. Circ Res. 104(9):1103-12. Abstract

Jovic, M., Kieken, F., Naslavsky, N., Sorgen P.L., and Caplan, S. (2009) EHD1-associated tubules contain phosphatidylinositol-4-phosphate and phosphatidylinositol-(4,5)-bisphosphate and are required for efficient recycling. Mol Biol Cell. 20(11):2731-43. Abstract

Sharma M, Jovic M, Kieken F, Naslavsky N, Sorgen PL, and Caplan S. (2009) A model for the role of EHD1-containing membrane tubules in endocytic recycling. Communicative & Integrative Biology. 2(5):431-3.

Verma V, Larsen BD, Coombs W, Lin X, Spagnol G, Sorgen PL, Taffet SM, and Delmar M. (2009) Novel pharmacophores of Connexin43 based on the "RXP" series of Cx43-binding peptides. Circ Res. 105:176-84.

Sorgen, P.L., and Delmar, M. (2008) Structure and organization of the cardiac gap junctions. In Cardiac Electrophysiology: From Cell to Bedside (Fifth Edition). Eds. Zipes, D.P. and Jalife, J. Saunders, Philadelphia, PA.

Bouvier, D., Kieken, F., Kellezi,A., and Sorgen, P.L. (2008) Structural Changes in the Carboxyl Terminus of the Gap Junction Protein Connexin40 caused by c-Src and Zonula Occludens-1. Cell Communication and Adhesion. 15:107-118. Abstract

Kellezi, A. Grosely, R., Kieken, F., Borgstahl, G.E.O., and Sorgen, P.L. (2008) Purification and Reconstitution of the Connexin43 Carboxyl Terminus attached to the 4th Transmembrane Domain in Detergent Micelles. Protein Purification and Expression. 59:215-222. Abstract

Duffy, H.S., Kieken, F., Mutsaers, N. Ciaccio, E.J., Coromilas, J., Wit, A.L., and Sorgen, P.L. (2008) Molecular Mechanisms of Connexin43 Lateralization in Ischemic Ventricular Myocytes after Coronary Artery Occlusion in the Canine Heart. Circulation. 116:67-68.

*Co-first author
#Corresponding author(s)
±Image from paper chosen for journal cover of J. Biomolecular NMR, 2008. 

Current Grants and Contracts:

Mechanisms of Gap Junction Regulation
National Institutes of Health (RO1)
12/01/2011 - 11/31/2015

Graduate Training in Structural Biology and Biophysics
U.S. Department of Education
08/15/2007 - 08/14/2012

Intercellular Communication and Impulse Propagation
National Institutes of Health (PO1)
09/01/2006 - 08/31/2011 

Regulation of EHD protein function by molecular partner interactions
National Institutes of Health
06/01/2010 - 05/31/2014 

Cancer Center Core Grant
National Institutes of Health (P30)
08/01/2011 - 07/31/2017 

Graduate Training in Structural Biology and Biophysics
U.S. Department of Education
08/15/2009 - 08/14/2014

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