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Kathleen M. Giangiacomo, PhD

 

Kathleen M. Giangiacomo, PhD

 

Associate Professor, Biochemistry

Telephone:  215-707-8258

Fax:  215-707-7536

Email: giang@temple.edu

 

Department of Biochemistry

 

Educational Background:

 

University of Pennsylvania

 

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Research Interests:

 

Potassium channels are integral membrane proteins that regulate numerous cellular processes such as muscle contraction, nerve transmission, hormone release and cell growth. The essence of potassium channel function in all of these processes relies on regulation or gating of transmembrane K+ flux through the channel pore. Our research focuses on probing the structure and function of two classes of voltage-gated potassium channels, the maxi-K and KV1 channels with peptide neurotoxins (alpha-KTx).

 

With their rigid, known 3D structure, and their exquisite selectivity for different potassium channels, alpha-KTx peptides are valuable molecular probes for identifying unique structural and functional features of the outer potassium channel pore. By exploring the molecular basis for alpha-KTx specificity, we have already identified novel structural features in the maxi-K and KV1.3 outer vestibules in collaboration with Dr. Ying-Duo Gao (Merck). alpha-KTx peptide affinities depend on the channel gating conformation. Consequently, mechanistic studies with these peptides may also reveal structural changes that couple channel gating and permeation.

 

The alpha-KTx peptides, IbTX and ChTX, display remarkable differences in their ability to discriminate between maxi-K channel complexes composed only of pore forming (alpha) subunits and those composed of alpha and auxiliary beta subunits. These associated beta subunits regulate maxi-K channel gating. With these alpha-KTx peptides as a tool, we are exploring the structural and functional relationships of alpha and beta1 subunits. In collaboration with Dr. Maria Garcia (Merck) we have identified beta1 subunit residues that modify ChTX block of single maxi-K channels and we revealed that beta1 subunits are associated with maxi-K channels in smooth but not skeletal muscle.

 

Maxi-K channels are important regulators of arterial tone. In a new research avenue, we are collaborating with Dr. Deborah Crabbe (Temple Cardiology Department), to explore the effects of chronic estrogen loss on maxi-K channel activity and expression in arterial smooth muscle.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

18815746. Giangiacomo KM, Becker J, Garsky C, Schmalhofer W, Garcia ML, Mullmann TJ, Novel alpha-KTx sites in the BK channel and comparative sequence analysis reveal distinguishing features of the BK and KV channel outer pore. Cell Biochem Biophys 52:1(47-58)2008

17439246. Giangiacomo KM, Becker J, Garsky C, Felix JP, Priest BT, Schmalhofer W, Garcia ML, Mullmann TJ, Revealing the molecular determinants of neurotoxin specificity for calcium-activated versus voltage-dependent potassium channels. Biochemistry 46:18(5358-64)2007 May 8

15208020. Giangiacomo KM, Ceralde Y, Mullmann TJ, Molecular basis of alpha-KTx specificity. Toxicon 43:8(877-86)2004 Jun 15

12220678. Schroeder N, Mullmann TJ, Schmalhofer WA, Gao YD, Garcia ML, Giangiacomo KM, Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi-K versus K(V) channels. FEBS Lett 527:1-3(298-302)2002 Sep 11

11551194. Mullmann TJ, Spence KT, Schroeder NE, Fremont V, Christian EP, Giangiacomo KM, Insights into alpha-K toxin specificity for K+ channels revealed through mutations in noxiustoxin. Biochemistry 40:37(10987-97)2001 Sep 18

10821684. Giangiacomo KM, Fremont V, Mullmann TJ, Hanner M, Cox RH, Garcia ML, Interaction of charybdotoxin S10A with single maxi-K channels: kinetics of blockade depend on the presence of the beta 1 subunit. Biochemistry 39:20(6115-22)2000 May 23

10029533. Mullmann TJ, Munujos P, Garcia ML, Giangiacomo KM, Electrostatic mutations in iberiotoxin as a unique tool for probing the electrostatic structure of the maxi-K channel outer vestibule. Biochemistry 38:8(2395-402)1999 Feb 23

9758866. Giangiacomo KM, Kamassah A, Harris G, McManus OB, Mechanism of maxi-K channel activation by dehydrosoyasaponin-I. J Gen Physiol 112:4(485-501)1998 Oct

7495817. Giangiacomo KM, Garcia-Calvo M, Knaus HG, Mullmann TJ, Garcia ML, McManus O, Functional reconstitution of the large-conductance, calcium-activated potassium channel purified from bovine aortic smooth muscle. Biochemistry 34:48(15849-62)1995 Dec 5

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