Biomedical Research Education & Training
Faculty Member

Eischen, Christine M., Ph.D.
Associate Professor of Pathology, Microbiology and Immunology
Associate Professor of Cancer Biology

Lab Url: http://CC-2210 MCN

Phone Number: 343-2303

Email Address: christine.eischen@vanderbilt.edu

Eischen, Christine's picture
Academic history
B.S., Creighton University
Ph.D., Mayo Clinic
Postdoc, St. Jude Children

Office Address   Mailing Address

CC-2210 MCN

Department of Pathology; C3321 MCN; 37232-2561


Research Description
The primary focus of the Eischen lab is on tumor initiation. We want to know how does a normal cell become a cancer cell. Specifically, we want to know what are the genes and pathways that contribute to or inhibit cellular transformation. We study the pathways, proteins, and recently, the miRNA that contribute to or inhibit tumor development. Lymphoma is the cancer that we have almost 2 decades of experience studying, and multiple projects utilize this expertise and several mouse models of lymphoma. However, lung, breast, and ovarian carcinomas are also studied in the lab.

Currently, there are three major areas of research focus that overlap in the Eischen lab.

The first area of research focus is on the oncogene Myc. We study Myc and its roles in proliferation, transformation, tumor development, and tumor cell maintenance. A large part of studying Myc is centered on the apoptosis that it causes when overexpressed in normal, untransformed cells, and the transcription it induces to drive proliferation. Myc induces the p53 pathway and suppression of the expression of anti-apoptotic Bcl-2 family members to induce apoptosis in normal cells. Cells acquire alterations that inactivate the ability of Myc to induce apoptosis. Moreover, Myc-induced transcription is still incompletely understood. We discovered a novel regulator of Myc called MTBP. There are four projects that focus on various aspects of Myc-induced tumor development.

The second area of research in the Eischen lab focuses on Mdm2 and Mdmx, two oncogenes best known for their negative regulation of the p53 tumor suppressor, and their roles in tumorigenesis. We discovered that both Mdm2 and Mdmx have p53-independent functions that contribute to tumorigenesis. We determined that Mdm2 and Mdmx regulate double-strand DNA break repair through interaction with Nbs1, a component of the Mre11/Rad50//Nbs1 DNA repair complex. We observed that increased expression of Mdm2 or Mdmx induces genome instability and increases transformation through a mechanism that is independent of p53. We are further characterizing this function with novel mouse models and investigating how this function can be capitalized on for the treatment of malignancies, half of which have inactivated p53. There are two projects that focus on Mdm2 and Mdmx in tumorigenesis.

The third area of research in the Eischen lab centers on the contribution miRNA have in tumor development. miRNA are small non-coding RNA that inhibit protein translation. We are utilizing lymphoma and lung cancer models to study miRNA in cancer. Our investigations focus on oncogene regulation of miRNA and whether they inhibit or contribute to tumor development. We have identified miRNA that are induced by Myc that lead apoptosis to protect cells from transformation. Another project focuses on a miRNA that appears to be a novel driver of lung tumor development. A third project is on miRNA that are altered in cutaneous T cell lymphoma and may serve as novel diagnostic markers for this malignancy.


There are open graduate student and postdoctoral fellowship positions. There are also opportunities for clinical fellows.

Publications
Adams, CM, Eischen, CM. Inactivation of p53 is insufficient to allow B cells and B cell lymphomas to survive without Dicer. Cancer Res, 2014

Carrillo, AM, Bouska, A, Arrate, MP, Eischen, CM. Mdmx promotes genomic instability independent of p53 and Mdm2. Oncogene, 0, 2014

Eischen, CM, Lozano, G. The Mdm Network and its Regulation of p53 Activities: A Rheostat of Cancer Risk. Hum Mutat, 2014

Grieb, BC, Chen, X, Eischen, CM. MTBP is Over-expressed in Triple Negative Breast Cancer and Contributes to its Growth and Survival. Mol Cancer Res, 2014

Grieb, BC, Gramling, MW, Arrate, MP, Chen, X, Beauparlant, SL, Haines, DS, Xiao, H, Eischen, CM. Oncogenic Protein MTBP Interacts with MYC to Promote Tumorigenesis. Cancer Res, 2014

McGirt, LY, Baerenwald, DA, Vonderheid, EC, Eischen, CM. Early changes in miRNA expression are predictive of response to extracorporeal photopheresis in cutaneous T-cell lymphoma. J Eur Acad Dermatol Venereol, 2014

Johnson, VE, Vonderheid, EC, Hess, AD, Eischen, CM, McGirt, LY. Genetic markers associated with progression in early mycosis fungoides. J Eur Acad Dermatol Venereol, 2013

McGirt, LY, Adams, CM, Baerenwald, DA, Zwerner, JP, Zic, JA, Eischen, CM. miR-223 Regulates Cell Growth and Targets Proto-Oncogenes in Mycosis Fungoides/Cutaneous T-Cell Lymphoma. J Invest Dermatol, 2013

Wells, CE, Bhaskara, S, Stengel, KR, Zhao, Y, Sirbu, B, Chagot, B, Cortez, D, Khabele, D, Chazin, WJ, Cooper, A, Jacques, V, Rusche, J, Eischen, CM, McGirt, LY, Hiebert, SW. Inhibition of histone deacetylase 3 causes replication stress in cutaneous T cell lymphoma. PLoS One, 8(7), e68915, 2013

Anderson, PD, McKissic, SA, Logan, M, Roh, M, Franco, OE, Wang, J, Doubinskaia, I, van der Meer, R, Hayward, SW, Eischen, CM, Eltoum, IE, Abdulkadir, SA. Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis. J Clin Invest, 122(5), 1907-19, 2012

Eischen, CM, Boyd, K. Decreased Mdm2 expression inhibits tumor development and extends survival independent of Arf and dependent on p53. PLoS One, 7(9), e46148, 2012

Gramling, MW, Eischen, CM. Suppression of Ras/Mapk pathway signaling inhibits Myc-induced lymphomagenesis. Cell Death Differ, 19(7), 1220-7, 2012

Melo, AN, Eischen, CM. Protecting the genome from mdm2 and mdmx. Genes Cancer, 3(3-4), 283-90, 2012

Cho, SH, Ahn, AK, Bhargava, P, Lee, CH, Eischen, CM, McGuinness, O, Boothby, M. Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family. Proc Natl Acad Sci U S A, 108(38), 15972-7, 2011

Lushnikova, T, Bouska, A, Odvody, J, Dupont, WD, Eischen, CM. Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression. Oncogene, 2011

Arrate, MP, Vincent, T, Odvody, J, Kar, R, Jones, SN, Eischen, CM. MicroRNA biogenesis is required for Myc-induced B-cell lymphoma development and survival. Cancer Res, 70(14), 6083-92, 2010

Odvody, J, Vincent, T, Arrate, MP, Grieb, B, Wang, S, Garriga, J, Lozano, G, Iwakuma, T, Haines, DS, Eischen, CM. A deficiency in Mdm2 binding protein inhibits Myc-induced B-cell proliferation and lymphomagenesis. Oncogene, 29(22), 3287-96, 2010

Bouska, A, Eischen, CM. Mdm2 Affects Genome Stability Independent of p53. Cancer Res, 69(5), 1697-701, 2009

Cho, SH, Goenka, S, Henttinen, T, Gudapati, P, Reinikainen, A, Eischen, CM, Lahesmaa, R, Boothby, M. PARP-14, a member of the B aggressive lymphoma (BAL) family, transduces survival signals in primary B cells. Blood, 2009 PMCID:2656269

Eischen, CM, Lozano, G. p53 and MDM2: Antagonists or Partners in Crime. Cancer Cell, 15(3), 161-2, 2009

Bouska, A, Lushnikova, T, Plaza, S, Eischen, CM. Mdm2 promotes genetic instability and transformation independent of p53. Mol Cell Biol, 28(15), 4862-74, 2008 PMCID:2493369

Mudhasani, R, Zhu, Z, Hutvagner, G, Eischen, CM, Lyle, S, Hall, LL, Lawrence, JB, Imbalzano, AN, Jones, SN. Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells. J Cell Biol, 181(7), 1055-63, 2008 PMCID:2442212

Iwakuma, T, Tochigi, Y, Van Pelt, CS, Caldwell, LC, Terzian, T, Parant, JM, Chau, GP, Koch, JG, Eischen, CM, Lozano, G. Mtbp haploinsufficiency in mice increases tumor metastasis. Oncogene, 2007

Wang, P, Lushnikova, T, Odvody, J, Greiner, TC, Jones, SN, Eischen, CM. Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells. Oncogene, 2007

Wang, P, Greiner, TC, Lushnikova, T, Eischen, CM. Decreased Mdm2 expression inhibits tumor development induced by loss of ARF. Oncogene, 25(26), 3708-18, 2006

Alt, JR, Bouska, A, Fernandez, MR, Cerny, RL, Xiao, H, Eischen, CM. Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. J Biol Chem, 280(19), 18771-81, 2005

Eischen, CM, Alt, JR, Wang, P. Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis and lymphoma development. Oncogene, 23(55), 8931-40, 2004

Alt, JR, Greiner, TC, Cleveland, JL, Eischen, CM. Mdm2 haplo-insufficiency profoundly inhibits Myc-induced lymphomagenesis. EMBO J, 22(6), 1442-50, 2003 PMCID:151074

Eischen, CM, Rehg, JE, Korsmeyer, SJ, Cleveland, JL. Loss of Bax alters tumor spectrum and tumor numbers in ARF-deficient mice. Cancer Res, 62(7), 2184-91, 2002

Eischen, CM, Packham, G, Nip, J, Fee, BE, Hiebert, SW, Zambetti, GP, Cleveland, JL. Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene, 20(48), 6983-93, 2001

Eischen, CM, Roussel, MF, Korsmeyer, SJ, Cleveland, JL. Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol Cell Biol, 21(22), 7653-62, 2001 PMCID:99936

Eischen, CM, Woo, D, Roussel, MF, Cleveland, JL. Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis. Mol Cell Biol, 21(15), 5063-70, 2001 PMCID:87232

Nip, J, Strom, DK, Eischen, CM, Cleveland, JL, Zambetti, GP, Hiebert, SW. E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation. Oncogene, 20(8), 910-20, 2001

Eischen, CM, Weber, JD, Roussel, MF, Sherr, CJ, Cleveland, JL. Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev, 13(20), 2658-69, 1999 PMCID:317106

Zindy, F, Eischen, CM, Randle, DH, Kamijo, T, Cleveland, JL, Sherr, CJ, Roussel, MF. Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev, 12(15), 2424-33, 1998 PMCID:317045

Eischen, CM, Kottke, TJ, Martins, LM, Basi, GS, Tung, JS, Earnshaw, WC, Leibson, PJ, Kaufmann, SH. Comparison of apoptosis in wild-type and Fas-resistant cells: chemotherapy-induced apoptosis is not dependent on Fas/Fas ligand interactions. Blood, 90(3), 935-43, 1997

Eischen, CM, Williams, BL, Zhang, W, Samelson, LE, Lynch, DH, Abraham, RT, Leibson, PJ. ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis. J Immunol, 159(3), 1135-9, 1997

Eischen, CM, Schilling, JD, Lynch, DH, Krammer, PH, Leibson, PJ. Fc receptor-induced expression of Fas ligand on activated NK cells facilitates cell-mediated cytotoxicity and subsequent autocrine NK cell apoptosis. J Immunol, 156(8), 2693-9, 1996


Postdoctoral Position Available
Yes

Postdoctoral Position Details
There is one immediate opening for a post-doctoral fellow interested in cancer initiation and one immediate opening for a post-doctoral fellow interested in hematopoiesis. Applications are invited from experienced and highly motivated individuals who are interested in genetic, molecular, or biochemical mechanisms of tumor development or hematopoiesis/immune response. My laboratory utilizes genetically engineered mouse models, primary cell culture, retroviral gene transfer technologies, protein purification, genomics, and patient sample analysis, to answer questions related to tumor initiation and lymphocyte biology.

Two cancer projects are currently available for post-doctoral fellows. The first project focuses on MTBP, a gene we discovered is a novel regulator of the MYC oncogene, and its role in lymphoma development and maintenance. The second project focuses on genes that contribute to lung adenocarcinoma initiation.

A hematopoiesis or immune response project is available. The project focuses on genes that contribute to hematopoietic cell stress-mediated bone marrow failure.

Applicants should have a strong background in at least two of the following: molecular biology, biochemistry, cell biology, and/or mouse models. Interested individuals should send a CV and contact information for three references to christine.eischen@vanderbilt.edu.

Updated Date
01/21/2015