Faculty Interests Database

Faculty Affairs: Faculty Interests Database Jan B. Hoek, Ph.D.

Pathology, Anatomy & Cell Biology

Vice-Chair, Research
Mailing Address Contact Information
1020 Locust Street JAH 269
Philadelphia, Pennsylvania 19107
United States
Phone: (215) 503-5016
Fax: 215-923-2218
Ph.D., University of Amsterdam, 1972

Expertise and Research Interests
Research in my laboratory is focused on the analysis of integrated signaling responses in liver and other tissues and on the adaptive or maladaptive modification of these responses by acute and chronic ethanol exposure. The following project are currently ongoing:
Analysis of growth factor signaling networks and related gene expression profiles in liver, using a combination of computational modeling and experimental studies;
Signaling events associated with the onset and progression of liver regeneration, with emphasis on the control of energy metabolism, purinergic signaling and AMP-activated protein kinase;
Mechanisms of ethanol-associated disturbance of cellular Ca2+ homeostasis and Ca2+ signaling and its role in adaptation and stress-responses in the liver;
Mechanisms of ethanol-induced suscpetibility to apoptotic signals in the liver.
Alcohol; ethanol; cellular signaling; calcium; growth factors; growth factor receptor; epidermal growth factor; receptor tyrosine kinase; mitogen activated protein kinase cascades; computational modeling; liver regeneration; energy metabolism; mitochondria; AMP-activated protein kinase; laboratory rat; partial hepatectomy; isolated hepatocytes; tissue cell culture; fluorescence microscopy.
  • Pubmed
  • Pastorino, J.G. and Hoek, J.B. Regulation of hexokinase binding to VDAC. J. Bioenergetics Biomembranes, 40, 171-182, 2008.
  • Juskeviciute, E., Vadigepalli, R. and Hoek, J.B. Temporal and functional profile of the transcriptional regulatory network in the early regenerative response to partial hepatectomy in the rat. BMC Genomics 9:527, November 2008.
  • Crumm, S.E., Cofan, M., Juskeviciute, E. and Hoek, J.B. Adenine nucleotide changes in the remnant liver: An early signal for regeneration after partial hepatectomy. Hepatology, 48, 898-908, 2008.
  • Pastorino, J.G. and Hoek, J.B. Integration of energy metabolism and control of apoptosis in tumor cells. In: Mitochondria and Cancer (Singh, K., Ed). Springer, New York, December 2008. (Review).
  • Birtwistle, M.R., Hatakeyama, M., Yumoto, N., Ogunnaike, B.A., Hoek, J.B. and Kholodenko, B.N. Ligand-dependent responses of the ErbB signaling network: Experimental and modeling analyses. Mol. Syst. Biol. 3:144, 2007 [Epub 2007, Nov 13].
  • Aksamitiene, E., Hoek, J.B., Kholodenko, B. and Kiyatkin, A. Multi-strip Western blotting to increase quantitative data output. Electrophoresis, 28:3163-3173, 2007.
  • Hajnoczky G. and Hoek J.B. (2007) Mitochondrial longevity pathways. Science 315:607-609, 2007 (Science Perspective)
  • Nesti, L.I., Caterson, E.J.,, Li W.J., Chang, R., McCann, T.D., Hoek, J.B. and Tuan, R.S. TGF-²1 calcium signaling in osteoblasts. J. Cell Biochem. 101:348-359, 2007.
  • Markevich, N., Tsyganov, M., Hoek, J.B. and Kholodenko, B.N. Long-range Signaling by Phosphoprotein Waves Arising from Bistability in Protein Kinase Cascades. Mol Systems Biol. 2:61, 2006 [Epub 2006 Nov 14].
  • Hoek, J.B. Metformin and the fate of fat. Gastroenterol. 130:2234-2237, 2006. (Editorial)
  • Kiyatkin A., Aksamitiene, E., Markevich, N.I., Borisov, N.M., Hoek, J.B. and Kholodenko, B.N. Scaffolding protein GAB1 sustains epidermal growth factor-induced mitogenic and survival signaling by multiple positive feedback loops. J. Biol. Chem. 281:19925-19938, 2006.
  • Borisov, N.M., Markevich, N.I., Hoek, J.B. and Kholodenko, B.N. Trading the micro-world of combinatorial complexity for the macro-world of protein interaction domains. Biosystems 83:152-166, 2006.
  • Pastorino,J.G., Hoek,J.B. and Shulga, N. Activation of glycogen synthase kinase 3-beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res. 65:10545-10554, 2005
  • Covarrubias, M.Y., Khan, R.L., Vadigepalli, R., Hoek, J.B. and Schwaber, J.S. Chronic alcohol exposure alters transcription broadly in a key integrative nucleus for homeostasis: the nucleus tractus solitarius. Physiol. Genomics 24:45-58, 2005.
  • Hajnoczky, G., Buzas, C.J., Pacher, P., Hoek, J.B. and Rubin, E. Alcohol and mitochondria in cardiac apoptosis: mechanisms and visualization. Alcohol Clin Exp Res. 29:693-701, 2005
  • Borisov N.M., Markevich N.I., Hoek J.B., Kholodenko B.N. Signaling through receptors and scaffolds: independent interactions reduce combinatorial complexity. Biophys J. 89:951-966, 2005
  • Shulga, N., Hoek, J.B. and Pastorino, J.G. Elevated PTEN levels account for the increased sensitivity of ethanol-exposed cells to TNF induced cytotoxicity. J. Biol. Chem. 280:9416-9424, 2005.
  • Hoek, J.B. and Pastorino, J.G. Cellular signaling mechanisms in alcohol-induced hepatic injury. Seminars in Liver Disease, 24, 257-272, 2004.
  • Markevich, N.I., Moehren, G., Demin, O.V., Kiyatkin, A.B., Hoek, J.B. and Kholodenko, B.N. Signaling processing at the Ras circuit: What shapes Ras activation patterns? Systems Biology, 1, 104-113, 2004
  • Markevich, N.I., Hoek, J.B. and Kholodenko, B.N. Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades . J. Cell Biol. 164, 353-359, 2004.
  • Pastorino, J.G., Shulga, N. and Hoek, J.B. TNFa-induced cell killing in ethanol-exposed cells depends on p38 MAPK signaling, but is independent of Bid and caspase-8. Am. J. Physiol., Gastrointest. Liver Physiol. 285, G503-516, 2003.
  • Pastorino, J.G. and Hoek, J.B. Hexokinase II: The integration of energy metabolism and control of apoptosis. Curr. Medic. Chem., 10, 1535-1551, 2003.
  • Davies, A.M., Hershman, S., Stabley, G.J., Hoek, J.B., Peterson, J. and Cahill, A. A Ca2+-induced mitochondrial permeability transition causes complete release of rat liver endonuclease G activity from its exclusive location within the mitochondrial intermembrane space. Identification of a novel endo-exonuclease activity residing within the mitochondrial matrix. Nucleic Acids Res. 31, 1364-1373, 2003.
  • Kholodenko, B.N., Bruggeman, F.J., Kiyatkin, A., Sontag, E., Westerhoff, H.V. and Hoek, J.B. Untangling the wires: A novel strategy to trace functional interactions in signaling and gene networks. Proc. Natl. Acad. Sci., U.S.A., 99, 12841-12846, 2002
  • Pastorino, J.G., Shulga, N. and Hoek, J.B. Mitochondrial binding of hexokinse II inhibits Bax induced cytochrome c release and apoptosis. Journal of Biological Chemistry. 277: 7610-7618, 2002
  • Moehren, G., Markevich, N., Demin, O., Kiyatkin, A., Goryanin, I., Hoek, J.B. and Kholodenko, B. Temperature dependence of EGF receptor signaling can be accounted for by a kinetic model. Biochemistry. 41: 306-320, 2002
  • Hoek, J.B. and Pastorino, J.G. Alcohol, oxidative stress, and liver cell injury. Alcohol, 27, 63-68, 2002.
  • Hoek, J.B., Cahill, A. and Pastorino, J.G. (2002) Alcohol and mitochondria: A dysfunctional relationship. Gastroenterol., 122, 2049-2063, 2002.
  • Donahue RJ, Razmara M, Hoek JB, Knudsen TB. Direct influence of the p53 tumor suppressor on mitochondrial biogenesis and function. FASEB Journal. 15(3): 635-44, Mar 2001
  • Kholodenko BN, Brown GC, Hoek JB. Diffusion control of protein phosphorylation in signal transduction pathways. Biochemical Journal. 350 Pt 3: 901-7, 2000
  • Wu, J., Liu, S.L., Zhu, J.L., Norton, P.A., Nojiri, S., Hoek, J.B. and Zern, M.A. Roles of tissue transglutaminase in ethanol-induced inhibition of hepatocyte proliferation and a1-adrenergic signal transduction. Journal of Biological Chemistry. 275: 22213-22219, 2000
  • Pastorino, J.G. and Hoek, J.B. Ethanol potentiates tumor necrosis factor-a cytotoxicity by promoting the mitochondrial permeability transition. Hepatology. 31: 1141-1152, 2000
  • Kholodenko, B.N., Hoek, J.B. and Westerhoff, H.V. Why signaling proteins should be recruited to cell membranes. Trends in Cell Biology. 10: 173-178, 2000
COS Profile

Last Updated by Jennifer Morris: Tuesday, September 28, 2010 5:07:46 PM

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