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Jeremy Hengst

TitleAssistant Professor
InstitutionCollege of Medicine
DepartmentPharmacology
Address500 University Drive Hershey PA 17033
Mailbox: R310
Phone7175314290

 Overview 
 overview
PREFERRED TITLE/ROLE:

Assistant Professor

EDUCATION:

B.S., Millersville University, 1995
Ph.D., Pennsylvania State University College of Medicine, 2002
Postdoctoral Studies, Pennsylvania State University College of Medicine, 2008

NARRATIVE:

Development of small-molecule sphingosine kinase inhibitors, role of sphingosine kinase in development/progression of tobacco-carcinogen induced lung cancer.
The primary research interest of our laboratory is focused on the identification of mechanisms involved in the oncogenic role of sphingosine kinase (SK). In cancer cells, dysregulation of cell growth and/or apoptosis is closely linked to the sphingolipid metabolites, ceramide and sphingosine-l-phosphate (S-1-P). Ceramide induces cell growth arrest and apoptosis whereas S-1-P, a further metabolite of ceramide, promotes cell growth and/or protects from apoptosis. Ample evidence indicates that S-1-P, formed by activation of SK, can serve as an intracellular second messenger which modulates signaling pathways critical for cancer cell growth and survival. In fact, S-1-P antagonizes apoptosis mediated by ceramide, a stress-induced sphingolipid metabolite, suggesting that the intracellular ratio of these two sphingolipid metabolites and consequent regulation of opposing signaling pathways, are important factors that determine the fate of cancer cells. It is our hypothesis that SK, which catalyzes formation of S-1-P, plays a pivotal role in regulation of cancer cell proliferation and/or survival. Currently, we are developing/optimizing small-molecule inhibitors of SK as anti-cancer therapeutic agents. Additionally, we are exploring the role of SK in the development and/or progression of lung cancer caused by carcinogens present in tobacco smoke. Understanding the role of SK in this process will allow us to validate our novel small-molecule SK inhibitors as potential anti-lung cancer therapeutic agents.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Dick TE, Hengst JA, Fox TE, Colledge AL, Kale VP, Sung SS, Sharma A, Amin S, Loughran TP, Kester M, Wang HG, Yun JK. The Apoptotic Mechanism of Action of the Sphingosine Kinase 1 Selective Inhibitor SKI-178 in Human Acute Myeloid Leukemia Cell Lines. J Pharmacol Exp Ther. 2015 Mar; 352(3):494-508.
    View in: PubMed
  2. Kale VP, Hengst JA, Desai DH, Dick TE, Choe KN, Colledge AL, Takahashi Y, Sung SS, Amin SG, Yun JK. A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion. Cancer Lett. 2014 Nov 28; 354(2):299-310.
    View in: PubMed
  3. Carkaci-Salli N, Salli U, Tekin I, Hengst JA, Zhao MK, Gilman TL, Andrews AM, Vrana KE. Functional characterization of the S41Y (C2755A) polymorphism of tryptophan hydroxylase 2. J Neurochem. 2014 Sep; 130(6):748-58.
    View in: PubMed
  4. Barth BM, Shanmugavelandy SS, Kaiser JM, McGovern C, Altinoglu EI, Haakenson JK, Hengst JA, Gilius EL, Knupp SA, Fox TE, Smith JP, Ritty TM, Adair JH, Kester M. PhotoImmunoNanoTherapy reveals an anticancer role for sphingosine kinase 2 and dihydrosphingosine-1-phosphate. ACS Nano. 2013 Mar 26; 7(3):2132-44.
    View in: PubMed
  5. Hengst JA, Yun JK. Sphingosine kinase: a key to solving the 'French Paradox'? Br J Pharmacol. 2012 Jul; 166(5):1603-4.
    View in: PubMed
  6. Madhunapantula SV, Hengst J, Gowda R, Fox TE, Yun JK, Robertson GP. Targeting sphingosine kinase-1 to inhibit melanoma. Pigment Cell Melanoma Res. 2012 Mar; 25(2):259-74.
    View in: PubMed
  7. Ali-Rahmani F, Hengst JA, Connor JR, Schengrund CL. Effect of HFE variants on sphingolipid expression by SH-SY5Y human neuroblastoma cells. Neurochem Res. 2011 Sep; 36(9):1687-96.
    View in: PubMed
  8. Hengst JA, Wang X, Sk UH, Sharma AK, Amin S, Yun JK. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg Med Chem Lett. 2010 Dec 15; 20(24):7498-502.
    View in: PubMed
  9. Karelia N, Desai D, Hengst JA, Amin S, Rudrabhatla SV, Yun J. Selenium-containing analogs of SAHA induce cytotoxicity in lung cancer cells. Bioorg Med Chem Lett. 2010 Nov 15; 20(22):6816-9.
    View in: PubMed
  10. Sharma AK, Sk UH, Gimbor MA, Hengst JA, Wang X, Yun J, Amin S. Synthesis and bioactivity of sphingosine kinase inhibitors and their novel aspirinyl conjugated analogs. Eur J Med Chem. 2010 Sep; 45(9):4149-56.
    View in: PubMed
  11. Hengst JA, Guilford JM, Conroy EJ, Wang X, Yun JK. Enhancement of sphingosine kinase 1 catalytic activity by deletion of 21 amino acids from the COOH-terminus. Arch Biochem Biophys. 2010 Feb 1; 494(1):23-31.
    View in: PubMed
  12. Hengst JA, Guilford JM, Fox TE, Wang X, Conroy EJ, Yun JK. Sphingosine kinase 1 localized to the plasma membrane lipid raft microdomain overcomes serum deprivation induced growth inhibition. Arch Biochem Biophys. 2009 Dec; 492(1-2):62-73.
    View in: PubMed
  13. Bayerl MG, Bruggeman RD, Conroy EJ, Hengst JA, King TS, Jimenez M, Claxton DF, Yun JK. Sphingosine kinase 1 protein and mRNA are overexpressed in non-Hodgkin lymphomas and are attractive targets for novel pharmacological interventions. Leuk Lymphoma. 2008 May; 49(5):948-54.
    View in: PubMed
  14. Itagaki K, Yun JK, Hengst JA, Yatani A, Hauser CJ, Spolarics Z, Deitch EA. Sphingosine 1-phosphate has dual functions in the regulation of endothelial cell permeability and Ca2+ metabolism. J Pharmacol Exp Ther. 2007 Oct; 323(1):186-91.
    View in: PubMed
  15. Francy JM, Nag A, Conroy EJ, Hengst JA, Yun JK. Sphingosine kinase 1 expression is regulated by signaling through PI3K, AKT2, and mTOR in human coronary artery smooth muscle cells. Biochim Biophys Acta. 2007 Apr; 1769(4):253-65.
    View in: PubMed
  16. Hengst JA, Bond JS. Transport of meprin subunits through the secretory pathway: role of the transmembrane and cytoplasmic domains and oligomerization. J Biol Chem. 2004 Aug 13; 279(33):34856-64.
    View in: PubMed
  17. Bertenshaw GP, Villa JP, Hengst JA, Bond JS. Probing the active sites and mechanisms of rat metalloproteases meprin A and B. Biol Chem. 2002 Jul-Aug; 383(7-8):1175-83.
    View in: PubMed
  18. Tsukuba T, Kadowaki T, Hengst JA, Bond JS. Chaperone interactions of the metalloproteinase meprin A in the secretory or proteasomal-degradative pathway. Arch Biochem Biophys. 2002 Jan 15; 397(2):191-8.
    View in: PubMed
  19. Sroka R, Ell C, Gottschalk W, Hengst J, Unsöld E. Homogeneous light application and monitoring of the applied power density during PDT. J Photochem Photobiol B. 1989 Jun; 3(3):456-8.
    View in: PubMed
  20. Hengst JA, Georgoff I, Isom HC, Jacob ST. Association of newly synthesized poly(A) polymerase with four distinct polypeptides. J Biol Chem. 1988 Dec 25; 263(36):19270-3.
    View in: PubMed
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