Thomas P. Stricker, M.D., Ph.D.

Assistant Professor

thomas.stricker@vanderbilt.edu
Faculty Appointments
Assistant Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Molecular Cell Biology, Washington University, Saint Louis, MissouriM.D., Medicine, Washington University, Saint Louis, MissouriB.S., University of Iowa, Iowa City, Iowa
Research Description
One of the surprising findings coming out of large cancer re-sequencing studies, such as The Cancer Genome Atlas (TCGA), was the large number of recurrent mutations in transcriptional regulators and chromatin remodeling enzymes. Research in my lab is focused on understanding how mutations in these genes contribute to the malignant phenotype. Projects in the lab analyze large, publicly available datasets, such as TCGA, with a focus on integrative analyses, as well as ChIPseq and RNAseq datasets generated in house in manipulatable cell line models.

Currently, research in the lab is focusing on mutation of chromatin remodeling enzymes in breast cancer. In particular, KMT2C/MLL3, which is mutated in about 7% of all estrogen receptor positive breast cancers, is a histone methyltransferase that creates the H3K4me1 mark at enhancers. We hypothesize that loss of MLL3/KMT2C function leads to a shift in the enhancer landscape, altering the sites available for estrogen receptor binding and thus changing gene transcription in breast cancer. A second project focuses on sequence-specific transcription factors that are recurrently mutated in breast cancer, such as FOXA1, GATA3, and TBX3. Evidence from mouse knockout models and human mendelian disorders suggest that these transcription factors have a function in determining cell identify in the developing breast. We are currently testing the hypothesis that these transcription factors form a genomic regulatory network, and disruption of that network by mutation destabilizes gene expression programs, contributing to malignancy.
Research Keywords
Cancer, breast cancer, genomics, ChIP-seq, RNAseq, Mutations, chromatin, transcription, epigenetics
Publications
Giltnane JM, Hutchinson KE, Stricker TP, Formisano L, Young CD, Estrada MV, Nixon MJ, Du L, Sanchez V, Ericsson PG, Kuba MG, Sanders ME, Mu XJ, Van Allen EM, Wagle N, Mayer IA, Abramson V, G¿mez H, Rizzo M, Toy W, Chandarlapaty S, Mayer EL, Christiansen J, Murphy D, Fitzgerald K, Wang K, Ross JS, Miller VA, Stephens PJ, Yelensky R, Garraway L, Shyr Y, Meszoely I, Balko JM, Arteaga CL. Genomic profiling of ER(+) breast cancers after short-term estrogen suppression reveals alterations associated with endocrine resistance. Sci Transl Med. 2017 Aug 8/9/2017; 9(402): PMID: 28794284, PII: 9/402/eaai7993, DOI: 10.1126/scitranslmed.aai7993, ISSN: 1946-6242.

Formisano L, Stauffer KM, Young CD, Bhola NE, Guerrero-Zotano AL, Jansen VM, Estrada MM, Hutchinson KE, Giltnane JM, Schwarz LJ, Lu Y, Balko JM, Deas O, Cairo S, Judde JG, Mayer IA, Sanders M, Dugger TC, Bianco R, Stricker T, Arteaga CL. Association of FGFR1 with ERamaintains ligand-independent ER transcription and mediates resistance to estrogen deprivation in ER+ breast cancer. Clin. Cancer Res [print-electronic]. 2017 Jul 7/27/2017; PMID: 28751448, PII: 1078-0432.CCR-17-1232, DOI: 10.1158/1078-0432.CCR-17-1232, ISSN: 1078-0432.

Hanker AB, Estrada MV, Bianchini G, Moore PD, Zhao J, Cheng F, Koch JP, Gianni L, Tyson DR, Sánchez V, Rexer BN, Sanders ME, Zhao Z, Stricker TP, Arteaga CL. Extracellular Matrix/Integrin Signaling Promotes Resistance to Combined Inhibition of HER2 and PI3K in HER2(+) Breast Cancer. Cancer Res [print-electronic]. 2017 Jun 6/15/2017; 77(12): 3280-92. PMID: 28396358, PMCID: PMC5482178, PII: 0008-5472.CAN-16-2808, DOI: 10.1158/0008-5472.CAN-16-2808, ISSN: 1538-7445.

Stricker TP, Brown CD, Bandlamudi C, McNerney M, Kittler R, Montoya V, Peterson A, Grossman R, White KP. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression. PLoS Genet. 2017 Mar; 13(3): e1006589. PMID: 28263985, PMCID: PMC5367891, PII: PGENETICS-D-14-02927, DOI: 10.1371/journal.pgen.1006589, ISSN: 1553-7404.

Williams MM, Lee L, Hicks DJ, Joly MM, Elion D, Rahman B, McKernan C, Sanchez V, Balko JM, Stricker T, Estrada MV, Cook RS. Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade. Mol. Cancer Res [print-electronic]. 2017 Mar; 15(3): 259-68. PMID: 28039357, PMCID: PMC5334148, PII: 1541-7786.MCR-16-0280-T, DOI: 10.1158/1541-7786.MCR-16-0280-T, ISSN: 1557-3125.

Shaver TM, Lehmann BD, Beeler JS, Li CI, Li Z, Jin H, Stricker TP, Shyr Y, Pietenpol JA. Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies. Cancer Res [print-electronic]. 2016 Aug 8/15/2016; 76(16): 4850-60. PMID: 27231203, PMCID: PMC4987189, PII: 0008-5472.CAN-16-0058, DOI: 10.1158/0008-5472.CAN-16-0058, ISSN: 1538-7445.

Kanteti R, Dhanasingh I, El-Hashani E, Riehm JJ, Stricker T, Nagy S, Zaborin A, Zaborina O, Biron D, Alverdy JC, Im HK, Siddiqui S, Padilla PA, Salgia R. C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype. Cancer Biol. Ther. 2016; 17(1): 91-103. PMID: 26574927, DOI: 10.1080/15384047.2015.1108495, ISSN: 1555-8576.

Barham W, Chen L, Tikhomirov O, Onishko H, Gleaves L, Stricker TP, Blackwell TS, Yull FE. Aberrant activation of NF-¿B signaling in mammary epithelium leads to abnormal growth and ductal carcinoma in situ. BMC Cancer. 2015 Sep 9/30/2015; 15: 647. PMID: 26424146, PMCID: PMC4590702, PII: 10.1186/s12885-015-1652-8, DOI: 10.1186/s12885-015-1652-8, ISSN: 1471-2407.

Young CD, Zimmerman LJ, Hoshino D, Formisano L, Hanker AB, Gatza ML, Morrison MM, Moore PD, Whitwell CA, Dave B, Stricker T, Bhola NE, Silva GO, Patel P, Brantley-Sieders DM, Levin M, Horiates M, Palma NA, Wang K, Stephens PJ, Perou CM, Weaver AM, O'Shaughnessy JA, Chang JC, Park BH, Liebler DC, Cook RS, Arteaga CL. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer. Mol. Cell Proteomics [print-electronic]. 2015 Jul; 14(7): 1959-76. PMID: 25953087, PMCID: PMC4587316, PII: M115.049783, DOI: 10.1074/mcp.M115.049783, ISSN: 1535-9484.

Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M, Rieke D, Endhardt K, Fang P, Brägelmann J, DeBoer R, El-Dinali M, Aktolga S, Lei Z, Tan P, Rozen SG, Salgia R, Weichselbaum RR, Lingen MW, Story MD, Ang KK, Cohen EE, White KP, Vokes EE, Seiwert TY. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin. Cancer Res [print-electronic]. 2015 Feb 2/15/2015; 21(4): 870-81. PMID: 25492084, PII: 1078-0432.CCR-14-2481, DOI: 10.1158/1078-0432.CCR-14-2481, ISSN: 1078-0432.

Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, Brown C, Pugh TJ, Stojanov P, Cho J, Lawrence MS, Getz G, Brägelmann J, DeBoer R, Weichselbaum RR, Langerman A, Portugal L, Blair E, Stenson K, Lingen MW, Cohen EE, Vokes EE, White KP, Hammerman PS. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin. Cancer Res [print-electronic]. 2015 Feb 2/1/2015; 21(3): 632-41. PMID: 25056374, PMCID: PMC4305034, PII: 1078-0432.CCR-13-3310, DOI: 10.1158/1078-0432.CCR-13-3310, ISSN: 1078-0432.

Khattri A, Zuo Z, Brägelmann J, Keck MK, El Dinali M, Brown CD, Stricker T, Munagala A, Cohen EE, Lingen MW, White KP, Vokes EE, Seiwert TY. Rare occurrence of EGFRvIII deletion in head and neck squamous cell carcinoma. Oral Oncol [print-electronic]. 2015 Jan; 51(1): 53-8. PMID: 25255959, PII: S1368-8375(14)00248-6, DOI: 10.1016/j.oraloncology.2014.08.014, ISSN: 1879-0593.

Cates JM, Stricker TP. Surgical resection margins in desmoid-type fibromatosis: a critical reassessment. Am. J. Surg. Pathol. 2014 Dec; 38(12): 1707-14. PMID: 25392923, PII: 00000478-201412000-00016, DOI: 10.1097/PAS.0000000000000276, ISSN: 1532-0979.

Cates JM, Stricker TP, Sturgeon D, Coffin CM. Desmoid-type fibromatosis-associated Gardner fibromas: prevalence and impact on local recurrence. Cancer Lett [print-electronic]. 2014 Oct 10/28/2014; 353(2): 176-81. PMID: 25064609, PII: S0304-3835(14)00367-X, DOI: 10.1016/j.canlet.2014.07.020, ISSN: 1872-7980.

Guo Y, Zhao S, Lehmann BD, Sheng Q, Shaver TM, Stricker TP, Pietenpol JA, Shyr Y. Detection of internal exon deletion with exon Del. BMC Bioinformatics. 2014 Oct 10/16/2014; 15: 332. PMID: 25322818, PMCID: PMC4288651, PII: 1471-2105-15-332, DOI: 10.1186/1471-2105-15-332, ISSN: 1471-2105.

Stricker TP, Morales La Madrid A, Chlenski A, Guerrero L, Salwen HR, Gosiengfiao Y, Perlman EJ, Furman W, Bahrami A, Shohet JM, Zage PE, Hicks MJ, Shimada H, Suganuma R, Park JR, So S, London WB, Pytel P, Maclean KH, Cohn SL. Validation of a prognostic multi-gene signature in high-risk neuroblastoma using the high throughput digital NanoString nCounter™ system. Mol Oncol [print-electronic]. 2014 May; 8(3): 669-78. PMID: 24560446, PMCID: PMC4004665, PII: S1574-7891(14)00024-6, DOI: 10.1016/j.molonc.2014.01.010, ISSN: 1878-0261.

Papp G, Krausz T, Stricker TP, Szendroi M, Sápi Z. SMARCB1 expression in epithelioid sarcoma is regulated by miR-206, miR-381, and miR-671-5p on Both mRNA and protein levels. Genes Chromosomes Cancer [print-electronic]. 2014 Feb; 53(2): 168-76. PMID: 24327545, DOI: 10.1002/gcc.22128, ISSN: 1098-2264.

Stricker TP, Henriksen KJ, Tonsgard JH, Montag AG, Krausz TN, Pytel P. Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation. Mod. Pathol [print-electronic]. 2013 Jul; 26(7): 930-43. PMID: 23370767, PII: modpathol2012242, DOI: 10.1038/modpathol.2012.242, ISSN: 1530-0285.

Papp G, Changchien YC, Péterfia B, Pecsenka L, Krausz T, Stricker TP, Khoor A, Donner L, Sápi Z. SMARCB1 protein and mRNA loss is not caused by promoter and histone hypermethylation in epithelioid sarcoma. Mod. Pathol [print-electronic]. 2013 Mar; 26(3): 393-403. PMID: 23174932, PII: modpathol2012190, DOI: 10.1038/modpathol.2012.190, ISSN: 1530-0285.

Balko JM, Stricker TP, Arteaga CL. The genomic map of breast cancer: which roads lead to better targeted therapies?. Breast Cancer Res. 2013; 15(4): 209. PMID: 23905624, PMCID: PMC3979080, PII: bcr3435, DOI: 10.1186/bcr3435, ISSN: 1465-542X.

Zou Z, Schmaier AA, Cheng L, Mericko P, Dickeson SK, Stricker TP, Santoro SA, Kahn ML. Negative regulation of activated alpha-2 integrins during thrombopoiesis. Blood [print-electronic]. 2009 Jun 6/18/2009; 113(25): 6428-39. PMID: 19258597, PII: blood-2008-08-175356, DOI: 10.1182/blood-2008-08-175356, ISSN: 1528-0020.

Edelson BT, Stricker TP, Li Z, Dickeson SK, Shepherd VL, Santoro SA, Zutter MM. Novel collectin/C1q receptor mediates mast cell activation and innate immunity. Blood [print-electronic]. 2006 Jan 1/1/2006; 107(1): 143-50. PMID: 16166590, PMCID: PMC1895357, PII: 2005-06-2218, DOI: 10.1182/blood-2005-06-2218, ISSN: 0006-4971.

Dumin JA, Dickeson SK, Stricker TP, Bhattacharyya-Pakrasi M, Roby JD, Santoro SA, Parks WC. Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen. J. Biol. Chem [print-electronic]. 2001 Aug 8/3/2001; 276(31): 29368-74. PMID: 11359786, PII: M104179200, DOI: 10.1074/jbc.M104179200, ISSN: 0021-9258.

Stricker TP, Dumin JA, Dickeson SK, Chung L, Nagase H, Parks WC, Santoro SA. Structural analysis of the alpha(2) integrin I domain/procollagenase-1 (matrix metalloproteinase-1) interaction. J. Biol. Chem [print-electronic]. 2001 Aug 8/3/2001; 276(31): 29375-81. PMID: 11359774, PII: M102217200, DOI: 10.1074/jbc.M102217200, ISSN: 0021-9258.

Snitsarev V, Budde T, Stricker TP, Cox JM, Krupa DJ, Geng L, Kay AR. Fluorescent detection of Zn(2+)-rich vesicles with Zinquin: mechanism of action in lipid environments. Biophys. J. 2001 Mar; 80(3): 1538-46. PMID: 11222314, PMCID: PMC1301345, PII: S0006-3495(01)76126-7, DOI: 10.1016/S0006-3495(01)76126-7, ISSN: 0006-3495.

Kay AR, Alfonso A, Alford S, Cline HT, Holgado AM, Sakmann B, Snitsarev VA, Stricker TP, Takahashi M, Wu LG. Imaging synaptic activity in intact brain and slices with FM1-43 in C. elegans, lamprey, and rat. Neuron. 1999 Dec; 24(4): 809-17. PMID: 10624945, PII: S0896-6273(00)81029-6, ISSN: 0896-6273.