Biomedical Research Education & Training
Faculty Member

Zinkel, Sandra S., M.D., Ph.D.
Associate Professor of Medicine
Associate Professor of Cell and Developmental Biology
Associate Professor of Cancer Biology

Lab Url: N/A

Phone Number: 615-936-1801

Email Address: sandra.zinkel@vanderbilt.edu

Zinkel, Sandra's picture
Academic history
B.S., Indiana University
B.S., Indiana University
Ph.D., Yale University
M.D., University of Chicago

Office Address   Mailing Address

Preston Research Building Rm 548

548 PRB 6307


Research Keywords
BCL-2 family, BID, programmed cell death, hematopoiesis, bone marrow failure, DNA damage response, leukemia,Apoptosis,Biochemistry,Cancer,Cell cycle,DNA repair,Knockout,Mass spectroscopy,Mouse,Phosphorylation,Proteomics,Signal transduction,Stem cells

Research Specialty
BCL-2 family, BID, programmed cell death, hematopoiesis, Stem cells, DNA damage response, leukemia, Apoptosis, Biochemistry, Cancer, Cell cycle, DNA repair, Knockout, Mass spectroscopy, Mouse, Phosphorylation, Proteomics, Signal transduction

Research Description
My lab is interested in understanding the mechanisms by which normal and malignant cells regulate programmed cell death. Multicellular organisms have devised a tightly regulated, genetically programmed mechanism of cell suicide to maintain homeostasis and to prevent propagation of genetically damaged cells. The discovery of the BCL-2 family of genes uncovered the underlying genetic mechanism of this regulation, as well as a class of oncogenes that governs cell death rather than cell proliferation.
There are two major pathways that regulation programmed cell death: apoptosis and programmed necrosis. Simply, apoptotic cells implode in a relatively immune silent manner. Necrotic cells explode, releasing cellular contents and inciting an immune response- beneficial in settings of infection, but detrimental in settings of chronic damage, where the inflammation eliicited by necrotic cell death amplifies cellular damage. Current studies focus on how programmed cell death regulates homeostasis in the hematopoietic (blood) system. We have found that unrestrained programmed necrosis leads to bone marrow failure in mice that closely resembles the human disease Myelodysplastic syndrome (MDS).
The projects in my lab use hematopoietic cell culture systems, mouse models, immunofluorescence, electron microscopy, as well as flow cytometry and cell death assays to understand the signals and protein interactions that direct hematopoietic cells to die by apoptosis or necrosis. In addition, we use our mouse models to determine the effects of inhibiting necrosis on bone marrow failure and transformation to leukemia. An additional focus is to dissect the mechanism of Bcl-2 family members in mouse models of leukemia. Our studies provide new insights into the interplay between apoptosis and necrosis, and their role in hematopoiesis, bone marrow failure, and leukemogenesis.

Publications
Liu, Y, Aiello, A, Zinkel, SS. Bid protects the mouse hematopoietic system following hydroxyurea-induced replicative stress. Cell Death Differ, 2012

Yin, H, Vergeade, A, Shi, Q, Zackert, WE, Gruenberg, KC, Bokiej, M, Amin, T, Ying, W, Masterson, TS, Zinkel, SS, Oates, JA, Boutaud, O, Roberts, LJ. Acetaminophen inhibits cytochrome c redox cycling induced lipid peroxidation. Biochem Biophys Res Commun, 423(2), 224-8, 2012

Liu, Y, Bertram, CC, Shi, Q, Zinkel, SS. Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress. Cell Death Differ, 18(5), 841-52, 2011

Liu, Y, Vaithiyalingam, S, Shi, Q, Chazin, WJ, Zinkel, SS. BID binds to Replication protein A and stimulates ATR function following replicative stress. Mol Cell Biol, 2011

Biswas, S, Shi, Q, Matise, L, Cleveland, S, Dave, U, Zinkel, S. A role for proapoptotic Bax and Bak in T-cell differentiation and transformation. Blood, 116(24), 5237-46, 2010

Danthi, P, Pruijssers, AJ, Berger, AK, Holm, GH, Zinkel, SS, Dermody, TS. Bid regulates the pathogenesis of neurotropic reovirus. PLoS Pathog, 6, e1000980, 2010 PMCID:2895667

Zinkel, SS. Investigation of the proapoptotic BCL-2 family member bid on the crossroad of the DNA damage response and apoptosis. Methods Enzymol, 442, 231-50, 2008

Zinkel, SS, Hurov, KE, Gross, A. Bid plays a role in the DNA damage response. Cell, 130(1), 9-10; author reply 10-1, 2007 PMCID:2895667

Zinkel, S, Gross, A, Yang, E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ, 2006

Wang, J, Iwasaki, H, Krivtsov, A, Febbo, PG, Thorner, AR, Ernst, P, Anastasiadou, E, Kutok, JL, Kogan, SC, Zinkel, SS, Fisher, JK, Hess, JL, Golub, TR, Armstrong, SA, Akashi, K, Korsmeyer, SJ. Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J, 24(2), 368-81, 2005 PMCID:545811

Zinkel, SS, Hurov, KE, Ong, C, Abtahi, FM, Gross, A, Korsmeyer, SJ. A role for proapoptotic BID in the DNA-damage response. Cell, 122(4), 579-91, 2005

Zinkel, SS, Ong, CC, Ferguson, DO, Iwasaki, H, Akashi, K, Bronson, RT, Kutok, JL, Alt, FW, Korsmeyer, SJ. Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes Dev, 17(2), 229-39, 2003 PMCID:195974

Plesnila, N, Zinkel, S, Amin-Hanjani, S, Qiu, J, Korsmeyer, SJ, Moskowitz, MA. Function of BID -- a molecule of the bcl-2 family -- in ischemic cell death in the brain. Eur Surg Res, 34(1-2), 37-41, 2002

Plesnila, N, Zinkel, S, Le, DA, Amin-Hanjani, S, Wu, Y, Qiu, J, Chiarugi, A, Thomas, SS, Kohane, DS, Korsmeyer, SJ, Moskowitz, MA. BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia. Proc Natl Acad Sci U S A, 98(26), 15318-23, 2001 PMCID:65027

Korsmeyer, SJ, Gross, A, Harada, H, Zha, J, Wang, K, Yin, XM, Wei, M, Zinkel, S. Death and survival signals determine active/inactive conformations of pro-apoptotic BAX, BAD, and BID molecules. Cold Spring Harb Symp Quant Biol, 64, 343-50, 1999

Yin, XM, Wang, K, Gross, A, Zhao, Y, Zinkel, S, Klocke, B, Roth, KA, Korsmeyer, SJ. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature, 400(6747), 886-91, 1999

Wang, X, Zinkel, S, Polonsky, K, Fuchs, E. Transgenic studies with a keratin promoter-driven growth hormone transgene: prospects for gene therapy. Proc Natl Acad Sci U S A, 94(1), 219-26, 1997 PMCID:19291

Zinkel, S, Fuchs, E. Skin cancer and transgenic mice. Semin Cancer Biol, 5(1), 77-90, 1994

Zinkel, SS, Pal, SK, Szeber??nyi, J, Cooper, GM. Identification of a negative regulatory element that inhibits c-mos transcription in somatic cells. Mol Cell Biol, 12(5), 2029-36, 1992 PMCID:364373

Pal, SK, Zinkel, SS, Kiessling, AA, Cooper, GM. c-mos expression in mouse oocytes is controlled by initiator-related sequences immediately downstream of the transcription initiation site. Mol Cell Biol, 11(10), 5190-6, 1991 PMCID:361551

Zinkel, SS, Crothers, DM. Catabolite activator protein-induced DNA bending in transcription initiation. J Mol Biol, 219(2), 201-15, 1991

Zinkel, SS, Crothers, DM. Comparative gel electrophoresis measurement of the DNA bend angle induced by the catabolite activator protein. Biopolymers, 29(1), 29-38, 1990

Zinkel, SS, Crothers, DM. DNA bend direction by phase sensitive detection. Nature, 328(6126), 178-81, 1987


Postdoctoral Position Available
Yes

Postdoctoral Position Details
I have an opening for a highly motivated post-doctoral fellow with a strong record of productivity. My laboratory studies the role of BCL-2 family members in cell cycle control, DNA repair and apoptosis following DNA damage (Zinkel et al., Cell 122:579-591(2005). Zinkel et al., Genes & Dev. 17:229-239 (2003).) We utilize molecular, cellular and biochemical approaches as well as mouse models to investigate the role of the pro-apoptotic family member BID in the DNA damage response and leukemogenesis.
Interested applicants should send a cover letter along with a curriculum vita and the names of three to five references to:
Sandra.zinkel@vanderbilt.edu

Updated Date
07/11/2014