Biomedical Research Education & Training
Faculty Member

Zinkel, Sandra S., M.D., Ph.D.
Assistant Professor of Medicine
Assistant Professor of Cancer Biology
Assistant Professor of Cell and Developmental 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, 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, DNA damage response, leukemia, Apoptosis, Biochemistry, Cancer, Cell cycle, DNA repair, Knockout, Mass spectroscopy, Mouse, Phosphorylation, Proteomics, Signal transduction, Stem cells

Research Description
My lab is interested in understanding the mechanisms by which normal and malignant cells regulate programmed cell death or apoptosis following DNA damage. 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.
Current studies focus on the pro-death BCL-2 family member BID. The deletion of BID in mice prolongs the lives of myeloid cells culminating in the development of a fatal disorder resembling the human disease chronic myelomonocytic leukemia (CMML). Our recent work has shown an additional role for BID in preserving genomic integrity that is distinct from its pro-apoptotic role. Following DNA damage, BID is phosphorylated by the DNA damage kinase ATM and plays a role in cell cycle checkpoint control. Cells initiate a complex series of responses subsequent to DNA damage including activation of cell cycle checkpoints, promoting DNA repair, or activating apoptosis. BID, with its dual function in apoptosis and the DNA damage response, is well situated to serve as a mediator in determining cell fate following DNA damage.
An additional focus of the lab is on the role of the Bcl-2 family of proteins in hematopoietic differentiation and stem cell function.
The projects in my lab use hematopoietic cell culture systems, mouse models, immunofluorescence, as well as apoptosis, cell cycle checkpoint and DNA repair assays to understand the signals and protein interactions that direct BID to assume an apoptotic or cell cycle checkpoint/DNA repair role following treatment with agents inducing DNA damage. 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 cell cycle checkpoint/DNA repair responses following DNA damage, and their role in myeloid homeostasis 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
07/24/2012