Sandra S. Zinkel, M.D., Ph.D.

Associate Professor

sandra.zinkel@vanderbilt.edu

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Faculty Appointments
Associate Professor of Medicine Associate Professor of Cell and Developmental BiologyAssociate Professor of Pathology, Microbiology and Immunology
Education
B.S., Music, Indiana University, Bloomington, IndianaPh.D., Molecular Biophysics and Biochemistry, Yale University, New Haven, ConnecticutB.S., Chemistry, Indiana University, Bloomington, IndianaM.D., Medicine, University of Chicago, Chicago, Illinois
Office Address
548 PRB
2220 Pierce Avenue
Nashville, TN 6307
Research Description
Our lab studies how inflammation in the bone marrow microenvironment impacts blood diseases such as clonal hematopoiesis, bone marrow failure (myelodysplastic syndrome (MDS) and leukemia and how inhibiting inflammation impacts disease.
We use single cell analysis of mouse models and human samples as well as studies in BioVU (in collaboration with Eric Gamazon) to determine gene pathways that predispose to progression to disease.
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), and find increased necrosis in human MDS bone marrow.
We are also interested in uncovering how genetically determined changes in expression of programmed cell death genes impacts susceptibility to human disease. We have utilized an integrative approach, leveraging mouse models as well as BioVU, to probe how genetically determined variations in gene expression can influence susceptibility to diseases such as myocardial infarction as well as bone marrow failure and leukemia. In addition, we use our mouse models to determine the effects of inhibiting necrosis on bone marrow failure and transformation to leukemia as well as to validate the findings from our BioVU studies. Our studies provide new insights into the the role of inflammatory cell death on the microenvironment and its impact on hematopoiesis, bone marrow failure, and leukemogenesis. An additional focus is to determine the impact of genetically determined alterations in cell death pathways on susceptibility to human disease, using BioVU, in collaboration with Dr. Eric Gamazon.
Research Keywords
Programmed cell death, necroptosis, inflammation, hematopoiesis, Stem cells, DNA damage response, leukemia, Apoptosis, Biochemistry, Cancer, Cell cycle, DNA repair, Knockout, Mass spectroscopy, Mouse, Phosphorylation, Proteomics, Signal transduction, BioVU, PrediXcan.
Publications
Wagner PN, Shi Q, Salisbury-Ruf CT, Zou J, Savona MR, Fedoriw Y, Zinkel SS. Increased Ripk1-mediated bone marrow necroptosis leads to myelodysplasia and bone marrow failure in mice. Blood [print-electronic]. 2018 Nov 11/9/2018; PMID: 30413413, PII: blood-2018-05-847335, DOI: 10.1182/blood-2018-05-847335, ISSN: 1528-0020.

Salisbury-Ruf CT, Bertram CC, Vergeade A, Lark DS, Shi Q, Heberling ML, Fortune NL, Okoye GD, Jerome WG, Wells QS, Fessel J, Moslehi J, Chen H, Roberts Ii LJ, Boutaud O, Gamazon E, Zinkel SS. Bid maintains mitochondrial cristae structure and protects against cardiac disease in an integrative genomics study. Elife [print-electronic]. 2018 Oct 10/3/2018; 7: PMID: 30281024, PII: 40907, DOI: 10.7554/eLife.40907, ISSN: 2050-084X.

Salisbury-Ruf CT, Bertram CC, Vergeade A, Lark DS, Shi Q, Heberling ML, Fortune NL, Okoye GD, Jerome WG, Wells QS, Fessel J, Moslehi J, Chen H, Roberts LJ, Boutaud O, Gamazon ER, Zinkel SS. Bid maintains mitochondrial cristae structure and function and protects against cardiac disease in an integrative genomics study. Elife. 2018 Oct 10/3/2018; 7: PMID: 30281024, PMCID: PMC6234033, PII: 40907, DOI: 10.7554/eLife.40907, ISSN: 2050-084X.

Vergeade A, Bertram CC, Bikineyeva AT, Zackert WE, Zinkel SS, May JM, Dikalov SI, Roberts LJ, Boutaud O. Cardiolipin fatty acid remodeling regulates mitochondrial function by modifying the electron entry point in the respiratory chain. Mitochondrion [print-electronic]. 2016 May; 28: 88-95. PMID: 27085476, PMCID: PMC4860904, PII: S1567-7249(16)30021-6, DOI: 10.1016/j.mito.2016.04.002, ISSN: 1872-8278.

Zhou T, Kinney MC, Scott LM, Zinkel SS, Rebel VI. Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research. Blood [print-electronic]. 2015 Aug 8/27/2015; 126(9): 1057-68. PMID: 26077396, PMCID: PMC4551359, PII: blood-2015-01-624239, DOI: 10.1182/blood-2015-01-624239, ISSN: 1528-0020.

Williams CS, Bradley AM, Chaturvedi R, Singh K, Piazuelo MB, Chen X, McDonough EM, Schwartz DA, Brown CT, Allaman MM, Coburn LA, Horst SN, Beaulieu DB, Choksi YA, Washington MK, Williams AD, Fisher MA, Zinkel SS, Peek RM, Wilson KT, Hiebert SW. MTG16 contributes to colonic epithelial integrity in experimental colitis. Gut [print-electronic]. 2013 Oct; 62(10): 1446-55. PMID: 22833394, PMCID: PMC3663894, PII: gutjnl-2011-301439, DOI: 10.1136/gutjnl-2011-301439, ISSN: 1468-3288.

Zinkel SS, Yin XM, Gross A. Rejuvenating Bi(d)ology. Oncogene [print-electronic]. 2013 Jul 7/4/2013; 32(27): 3213-9. PMID: 23069655, PMCID: PMC4037911, PII: onc2012454, DOI: 10.1038/onc.2012.454, ISSN: 1476-5594.

Zinkel SS, Yin XM, Gross A. Rejuvenating Bi(d)ology. Oncogene [print-electronic]. 2013 Jul 7/4/2013; 32(27): 3213-9. PMID: 23069655, PMCID: PMC4037911, PII: onc2012454, DOI: 10.1038/onc.2012.454, ISSN: 1476-5594.

Biswas S, Shi Q, Wernick A, Aiello A, Zinkel SS. The loss of the BH3-only Bcl-2 family member Bid delays T-cell leukemogenesis in Atm-/- mice. Cell Death Differ [print-electronic]. 2013 Jul; 20(7): 869-77. PMID: 23470523, PMCID: PMC3679453, PII: cdd201316, DOI: 10.1038/cdd.2013.16, ISSN: 1476-5403.

Biswas S, Shi Q, Wernick A, Aiello A, Zinkel SS. The loss of the BH3-only Bcl-2 family member Bid delays T-cell leukemogenesis in Atm-/- mice. Cell Death Differ [print-electronic]. 2013 Jul; 20(7): 869-77. PMID: 23470523, PMCID: PMC3679453, PII: cdd201316, DOI: 10.1038/cdd.2013.16, ISSN: 1476-5403.

Liu Y, Aiello A, Zinkel SS. Bid protects the mouse hematopoietic system following hydroxyurea-induced replicative stress. Cell Death Differ [print-electronic]. 2012 Oct; 19(10): 1602-12. PMID: 22522598, PMCID: PMC3438491, PII: cdd201238, DOI: 10.1038/cdd.2012.38, ISSN: 1476-5403.

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 [print-electronic]. 2012 Jun 6/29/2012; 423(2): 224-8. PMID: 22634010, PMCID: PMC3389218, PII: S0006-291X(12)00935-7, DOI: 10.1016/j.bbrc.2012.05.058, ISSN: 1090-2104.

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 [print-electronic]. 2011 Nov; 31(21): 4298-309. PMID: 21859891, PMCID: PMC3209332, PII: MCB.05737-11, DOI: 10.1128/MCB.05737-11, ISSN: 1098-5549.

Liu Y, Bertram CC, Shi Q, Zinkel SS. Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress. Cell Death Differ [print-electronic]. 2011 May; 18(5): 841-52. PMID: 21113148, PMCID: PMC3074003, PII: cdd2010151, DOI: 10.1038/cdd.2010.151, ISSN: 1476-5403.

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 [print-electronic]. 2010 Dec 12/9/2010; 116(24): 5237-46. PMID: 20813900, PMCID: PMC3012541, PII: blood-2010-04-279687, DOI: 10.1182/blood-2010-04-279687, ISSN: 1528-0020.

Danthi P, Pruijssers AJ, Berger AK, Holm GH, Zinkel SS, Dermody TS. Bid regulates the pathogenesis of neurotropic reovirus. PLoS Pathog. 2010; 6: e1000980. PMID: 20617182, PMCID: PMC2895667, DOI: 10.1371/journal.ppat.1000980, ISSN: 1553-7374.

Zinkel SS. Investigation of the proapoptotic BCL-2 family member bid on the crossroad of the DNA damage response and apoptosis. Meth. Enzymol. 2008; 442: 231-50. PMID: 18662573, PII: S0076-6879(08)01412-2, DOI: 10.1016/S0076-6879(08)01412-2, ISSN: 1557-7988.

Zinkel SS, Hurov KE, Gross A. Bid plays a role in the DNA damage response [letter]. Cell. 2007 Jul 7/13/2007; 130(1): 9-10; author reply 10. PMID: 17632047, PII: S0092-8674(07)00840-9, DOI: 10.1016/j.cell.2007.06.035, ISSN: 0092-8674.

Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ [print-electronic]. 2006 Aug; 13(8): 1351-9. PMID: 16763616, PII: 4401987, DOI: 10.1038/sj.cdd.4401987, ISSN: 1350-9047.

Zinkel SS, Hurov KE, Ong C, Abtahi FM, Gross A, Korsmeyer SJ. A role for proapoptotic BID in the DNA-damage response. Cell. 2005 Aug 8/26/2005; 122(4): 579-91. PMID: 16122425, PII: S0092-8674(05)00641-0, DOI: 10.1016/j.cell.2005.06.022, ISSN: 0092-8674.

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 [print-electronic]. 2005 Jan 1/26/2005; 24(2): 368-81. PMID: 15635450, PMCID: PMC545811, PII: 7600521, DOI: 10.1038/sj.emboj.7600521, ISSN: 0261-4189.

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. 2003 Jan 1/15/2003; 17(2): 229-39. PMID: 12533511, PMCID: PMC195974, DOI: 10.1101/gad.1045603, ISSN: 0890-9369.

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. 2002 Jan; 34(1-2): 37-41. PMID: 11867899, PII: 48885, DOI: 48885, ISSN: 0014-312X.

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 [print-electronic]. 2001 Dec 12/18/2001; 98(26): 15318-23. PMID: 11742085, PMCID: PMC65027, PII: 261323298, DOI: 10.1073/pnas.261323298, ISSN: 0027-8424.

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. 1999 Aug 8/26/1999; 400(6747): 886-91. PMID: 10476969, DOI: 10.1038/23730, ISSN: 0028-0836.

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. 1999; 64: 343-50. PMID: 11232306, ISSN: 0091-7451.

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. 1997 Jan 1/7/1997; 94(1): 219-26. PMID: 8990189, PMCID: PMC19291, ISSN: 0027-8424.

Zinkel S, Fuchs E. Skin cancer and transgenic mice. Semin. Cancer Biol. 1994 Feb; 5(1): 77-90. PMID: 8186391, ISSN: 1044-579X.

Zinkel SS, Pal SK, Szeberényi J, Cooper GM. Identification of a negative regulatory element that inhibits c-mos transcription in somatic cells. Mol. Cell. Biol. 1992 May; 12(5): 2029-36. PMID: 1533271, PMCID: PMC364373, ISSN: 0270-7306.

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. 1991 Oct; 11(10): 5190-6. PMID: 1833632, PMCID: PMC361551, ISSN: 0270-7306.

Zinkel SS, Crothers DM. Catabolite activator protein-induced DNA bending in transcription initiation. J. Mol. Biol. 1991 May 5/20/1991; 219(2): 201-15. PMID: 1645410, PII: 0022-2836(91)90562-K, ISSN: 0022-2836.

Zinkel SS, Crothers DM. Comparative gel electrophoresis measurement of the DNA bend angle induced by the catabolite activator protein. Biopolymers. 1990 Jan; 29(1): 29-38. PMID: 2158360, DOI: 10.1002/bip.360290106, ISSN: 0006-3525.

Zinkel SS, Crothers DM. DNA bend direction by phase sensitive detection. Nature. 1987 Jul 7/9/1987; 328(6126): 178-81. PMID: 3600796, DOI: 10.1038/328178a0, ISSN: 0028-0836.

Available Postdoctoral Position Details
Posted: 2/14/2020

The Zinkel Lab in the Department of Medicine at Vanderbilt University School of Medicine is seeking a highly-motivated individual to join our team. Our lab studies how inflammation in the bone marrow microenvironment impacts blood diseases such as clonal hematopoiesis, bone marrow failure (myelodysplastic syndrome (MDS) and leukemia and how inhibiting inflammation impacts disease. We use single cell analysis of mouse models and human samples as well as studies in BioVU (in collaboration with Eric Gamazon) to determine gene pathways that predispose to progression to disease. The successful candidate will have a PhD and/or MD with experience in molecular and cellular biology and a solid publication record. Vanderbilt offers a highly collaborative research environment focused on interdisciplinary research. Please send a curriculum vita, the names of three references, and a letter describing your research interests to: Dr. Sandra Zinkel (Sandra.zinkel@VUMC.org)