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Lisa Shantz

TitleAssociate Professor
InstitutionCollege of Medicine
DepartmentCellular and Molecular Physiology
Address500 University Drive Hershey PA 17033
Mailbox: 4731C
Phone7175311562

 Overview 
 overview
PREFERRED TITLE/ROLE:

Associate Professor of Cellular and Molecular Physiology

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

Penn State Hershey Cancer Institute

GRADUATE PROGRAM AFFILIATIONS:

Cellular and Molecular Physiology, Biomedical Sciences, MD/PhD Degree Program

EDUCATION:

B.S. University of Scranton, 1984
Ph.D., Johns Hopkins University School of Medicine, 1989

NARRATIVE:

Our long-term goal is to better understand the molecular signaling cascades involved in non-melanoma skin carcinogenesis (NMSC) in order to identify novel therapeutic targets. NMSC is the most common form of human cancer, and estimates suggest that over 1.5 million new cases of skin cancer will be diagnosed this year. Although most skin cancers are easily treated, a sub-population of people are at higher risk, and about 10,000 Americans a year die from skin cancer. An increasing number of these people have received organ transplants. Because transplant patients take immunosuppressive drugs, they are at a much higher risk for the development of cancers in general and skin cancer in particular. With the increasing number of organ transplant recipients, targets for therapy and prevention of skin cancer will become even more important. Our research focuses on the polyamine pathway and mTOR-dependent pathways in early skin cancer development. There is strong experimental evidence indicating the location of epidermal stem cells that are modified by carcinogen exposure is in the hair follicle bulge. By directing expression of transgenes to this region of the epidermis, we can modify gene expression in stem cells and ask what effect these genetic alterations have on tumor development. Using transgenic models, we were the first to show a link between induction of the Raf/MEK/ERK pathway and increased ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis, in skin tumors. Importantly, we have established that high ODC activity is a necessary component of MEK-induced skin tumor development, and both antizyme (AZ), which binds to ODC and causes it to be degraded, and DFMO, a suicide inactivator of ODC, are a powerful suppressors of these tumors. Current work explores the role of mTOR-dependent pathways in skin carcinogenesis in response to both chemical carcinogens and UV light using mice with conditional deletion of mTOR, the mTORC1 component raptor, or the mTORC2 component rictor.





 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. Carr TD, Feehan RP, Hall MN, Rüegg MA, Shantz LM. Conditional disruption of rictor demonstrates a direct requirement for mTORC2 in skin tumor development and continued growth of established tumors. Carcinogenesis. 2015 Apr; 36(4):487-97.
    View in: PubMed
  2. Carr TD, DiGiovanni J, Lynch CJ, Shantz LM. Inhibition of mTOR suppresses UVB-induced keratinocyte proliferation and survival. Cancer Prev Res (Phila). 2012 Dec; 5(12):1394-404.
    View in: PubMed
  3. Zhang Y, Cheng Y, Ren X, Hori T, Huber-Keener KJ, Zhang L, Yap KL, Liu D, Shantz L, Qin ZH, Zhang S, Wang J, Wang HG, Shih IeM, Yang JM. Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis. Cancer Res. 2012 Aug 15; 72(16):4262-75.
    View in: PubMed
  4. Shi C, Cooper TK, McCloskey DE, Glick AB, Shantz LM, Feith DJ. S-adenosylmethionine decarboxylase overexpression inhibits mouse skin tumor promotion. Carcinogenesis. 2012 Jul; 33(7):1310-8.
    View in: PubMed
  5. Origanti S, Nowotarski SL, Carr TD, Sass-Kuhn S, Xiao L, Wang JY, Shantz LM. Ornithine decarboxylase mRNA is stabilized in an mTORC1-dependent manner in Ras-transformed cells. Biochem J. 2012 Feb 15; 442(1):199-207.
    View in: PubMed
  6. Giordano E, Hillary RA, Vary TC, Pegg AE, Sumner AD, Caldarera CM, Zhang XQ, Song J, Wang J, Cheung JY, Shantz LM. Overexpression of ornithine decarboxylase decreases ventricular systolic function during induction of cardiac hypertrophy. Amino Acids. 2012 Feb; 42(2-3):507-18.
    View in: PubMed
  7. Nowotarski SL, Origanti S, Shantz LM. Posttranscriptional regulation of ornithine decarboxylase. Methods Mol Biol. 2011; 720:279-92.
    View in: PubMed
  8. Nowotarski SL, Shantz LM. Cytoplasmic accumulation of the RNA-binding protein HuR stabilizes the ornithine decarboxylase transcript in a murine nonmelanoma skin cancer model. J Biol Chem. 2010 Oct 8; 285(41):31885-94.
    View in: PubMed
  9. Govoni M, Bonavita F, Shantz LM, Guarnieri C, Giordano E. Overexpression of ornithine decarboxylase increases myogenic potential of H9c2 rat myoblasts. Amino Acids. 2010 Feb; 38(2):541-7.
    View in: PubMed
  10. Levin VA, Jochec JL, Shantz LM, Aldape KD. Relationship between ornithine decarboxylase levels in anaplastic gliomas and progression-free survival in patients treated with DFMO-PCV chemotherapy. Int J Cancer. 2007 Nov 15; 121(10):2279-83.
    View in: PubMed
  11. Deignan JL, Livesay JC, Shantz LM, Pegg AE, O'Brien WE, Iyer RK, Cederbaum SD, Grody WW. Polyamine homeostasis in arginase knockout mice. Am J Physiol Cell Physiol. 2007 Oct; 293(4):C1296-301.
    View in: PubMed
  12. Feith DJ, Shantz LM, Shoop PL, Keefer KA, Prakashagowda C, Pegg AE. Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion-sensitive and promotion-resistant genetic backgrounds. Mol Carcinog. 2007 Jun; 46(6):453-65.
    View in: PubMed
  13. Origanti S, Shantz LM. Ras transformation of RIE-1 cells activates cap-independent translation of ornithine decarboxylase: regulation by the Raf/MEK/ERK and phosphatidylinositol 3-kinase pathways. Cancer Res. 2007 May 15; 67(10):4834-42.
    View in: PubMed
  14. Shantz LM, Levin VA. Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential. Amino Acids. 2007 Aug; 33(2):213-23.
    View in: PubMed
  15. Kim SW, Mangold U, Waghorne C, Mobascher A, Shantz L, Banyard J, Zetter BR. Regulation of cell proliferation by the antizyme inhibitor: evidence for an antizyme-independent mechanism. J Cell Sci. 2006 Jun 15; 119(Pt 12):2583-91.
    View in: PubMed
  16. Tantini B, Fiumana E, Cetrullo S, Pignatti C, Bonavita F, Shantz LM, Giordano E, Muscari C, Flamigni F, Guarnieri C, Stefanelli C, Caldarera CM. Involvement of polyamines in apoptosis of cardiac myoblasts in a model of simulated ischemia. J Mol Cell Cardiol. 2006 Jun; 40(6):775-82.
    View in: PubMed
  17. Feith DJ, Origanti S, Shoop PL, Sass-Kuhn S, Shantz LM. Tumor suppressor activity of ODC antizyme in MEK-driven skin tumorigenesis. Carcinogenesis. 2006 May; 27(5):1090-8.
    View in: PubMed
  18. Nisenberg O, Pegg AE, Welsh PA, Keefer K, Shantz LM. Overproduction of cardiac S-adenosylmethionine decarboxylase in transgenic mice. Biochem J. 2006 Jan 1; 393(Pt 1):295-302.
    View in: PubMed
  19. Feith DJ, Bol DK, Carboni JM, Lynch MJ, Sass-Kuhn S, Shoop PL, Shantz LM. Induction of ornithine decarboxylase activity is a necessary step for mitogen-activated protein kinase kinase-induced skin tumorigenesis. Cancer Res. 2005 Jan 15; 65(2):572-8.
    View in: PubMed
  20. Levin VA, Jochec JL, Shantz LM, Koch PE, Pegg AE. Tissue-based assay for ornithine decarboxylase to identify patients likely to respond to difluoromethylornithine. J Histochem Cytochem. 2004 Nov; 52(11):1467-74.
    View in: PubMed
  21. Ikeguchi Y, Wang X, McCloskey DE, Coleman CS, Nelson P, Hu G, Shantz LM, Pegg AE. Characterization of transgenic mice with widespread overexpression of spermine synthase. Biochem J. 2004 Aug 1; 381(Pt 3):701-7.
    View in: PubMed
  22. Shantz LM. Transcriptional and translational control of ornithine decarboxylase during Ras transformation. Biochem J. 2004 Jan 1; 377(Pt 1):257-64.
    View in: PubMed
  23. Pegg AE, Feith DJ, Fong LY, Coleman CS, O'Brien TG, Shantz LM. Transgenic mouse models for studies of the role of polyamines in normal, hypertrophic and neoplastic growth. Biochem Soc Trans. 2003 Apr; 31(2):356-60.
    View in: PubMed
  24. Shantz LM, Guo Y, Sawicki JA, Pegg AE, O'Brien TG. Overexpression of a dominant-negative ornithine decarboxylase in mouse skin: effect on enzyme activity and papilloma formation. Carcinogenesis. 2002 Apr; 23(4):657-64.
    View in: PubMed
  25. Feith DJ, Shantz LM, Pegg AE. Targeted antizyme expression in the skin of transgenic mice reduces tumor promoter induction of ornithine decarboxylase and decreases sensitivity to chemical carcinogenesis. Cancer Res. 2001 Aug 15; 61(16):6073-81.
    View in: PubMed
  26. Shantz LM, Feith DJ, Pegg AE. Targeted overexpression of ornithine decarboxylase enhances beta-adrenergic agonist-induced cardiac hypertrophy. Biochem J. 2001 Aug 15; 358(Pt 1):25-32.
    View in: PubMed
  27. Lopatin AN, Shantz LM, Mackintosh CA, Nichols CG, Pegg AE. Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. J Mol Cell Cardiol. 2000 Nov; 32(11):2007-24.
    View in: PubMed
  28. Mackintosh CA, Feith DJ, Shantz LM, Pegg AE. Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy. Biochem J. 2000 Sep 15; 350 Pt 3:645-53.
    View in: PubMed
  29. Kimball SR, Shantz LM, Horetsky RL, Jefferson LS. Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6. J Biol Chem. 1999 Apr 23; 274(17):11647-52.
    View in: PubMed
  30. Shantz LM, Pegg AE. Translational regulation of ornithine decarboxylase and other enzymes of the polyamine pathway. Int J Biochem Cell Biol. 1999 Jan; 31(1):107-22.
    View in: PubMed
  31. Pegg AE, Xiong H, Feith DJ, Shantz LM. S-adenosylmethionine decarboxylase: structure, function and regulation by polyamines. Biochem Soc Trans. 1998 Nov; 26(4):580-6.
    View in: PubMed
  32. Shantz LM, Pegg AE. Ornithine decarboxylase induction in transformation by H-Ras and RhoA. Cancer Res. 1998 Jul 1; 58(13):2748-53.
    View in: PubMed
  33. Shantz LM, Pegg AE. Assay of mammalian S-adenosylmethionine decarboxylase activity. Methods Mol Biol. 1998; 79:45-9.
    View in: PubMed
  34. Ruan H, Shantz LM, Pegg AE, Morris DR. The upstream open reading frame of the mRNA encoding S-adenosylmethionine decarboxylase is a polyamine-responsive translational control element. J Biol Chem. 1996 Nov 22; 271(47):29576-82.
    View in: PubMed
  35. Shantz LM, Coleman CS, Pegg AE. Expression of an ornithine decarboxylase dominant-negative mutant reverses eukaryotic initiation factor 4E-induced cell transformation. Cancer Res. 1996 Nov 15; 56(22):5136-40.
    View in: PubMed
  36. Shantz LM, Hu RH, Pegg AE. Regulation of ornithine decarboxylase in a transformed cell line that overexpresses translation initiation factor eIF-4E. Cancer Res. 1996 Jul 15; 56(14):3265-9.
    View in: PubMed
  37. Pegg AE, Shantz LM, Coleman CS. Ornithine decarboxylase as a target for chemoprevention. J Cell Biochem Suppl. 1995; 22:132-8.
    View in: PubMed
  38. Pegg AE, Shantz LM, Coleman CS. Ornithine decarboxylase: structure, function and translational regulation. Biochem Soc Trans. 1994 Nov; 22(4):846-52.
    View in: PubMed
  39. Stanley BA, Shantz LM. S-adenosylmethionine decarboxylase structure-function relationships. Biochem Soc Trans. 1994 Nov; 22(4):863-9.
    View in: PubMed
  40. Shantz LM, Viswanath R, Pegg AE. Role of the 5'-untranslated region of mRNA in the synthesis of S-adenosylmethionine decarboxylase and its regulation by spermine. Biochem J. 1994 Sep 15; 302 ( Pt 3):765-72.
    View in: PubMed
  41. Shantz LM, Pegg AE. Overproduction of ornithine decarboxylase caused by relief of translational repression is associated with neoplastic transformation. Cancer Res. 1994 May 1; 54(9):2313-6.
    View in: PubMed
  42. Stanley BA, Shantz LM, Pegg AE. Expression of mammalian S-adenosylmethionine decarboxylase in Escherichia coli. Determination of sites for putrescine activation of activity and processing. J Biol Chem. 1994 Mar 18; 269(11):7901-7.
    View in: PubMed
  43. Shantz LM, Holm I, Jänne OA, Pegg AE. Regulation of S-adenosylmethionine decarboxylase activity by alterations in the intracellular polyamine content. Biochem J. 1992 Dec 1; 288 ( Pt 2):511-8.
    View in: PubMed
  44. Shantz LM, Stanley BA, Secrist JA, Pegg AE. Purification of human S-adenosylmethionine decarboxylase expressed in Escherichia coli and use of this protein to investigate the mechanism of inhibition by the irreversible inhibitors, 5'-deoxy-5'-[(3-hydrazinopropyl)methylamino]adenosine and 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. Biochemistry. 1992 Jul 28; 31(29):6848-55.
    View in: PubMed
  45. Shantz LM, Talalay P, Gordon GB. Mechanism of inhibition of growth of 3T3-L1 fibroblasts and their differentiation to adipocytes by dehydroepiandrosterone and related steroids: role of glucose-6-phosphate dehydrogenase. Proc Natl Acad Sci U S A. 1989 May; 86(10):3852-6.
    View in: PubMed
  46. Hamburger AW, Parnes H, Gordon GB, Shantz LM, O'Donnell KA, Aisner J. Megestrol acetate-induced differentiation of 3T3-L1 adipocytes in vitro. Semin Oncol. 1988 Apr; 15(2 Suppl 1):76-8.
    View in: PubMed
  47. Gordon GB, Shantz LM, Talalay P. Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone. Adv Enzyme Regul. 1987; 26:355-82.
    View in: PubMed
  48. Gordon GB, Newitt JA, Shantz LM, Weng DE, Talalay P. Inhibition of the conversion of 3T3 fibroblast clones to adipocytes by dehydroepiandrosterone and related anticarcinogenic steroids. Cancer Res. 1986 Jul; 46(7):3389-95.
    View in: PubMed
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