Justin M. Balko, Pharm.D., Ph.D.

Assistant Professor

justin.balko@vanderbilt.edu
Faculty Appointments
Assistant Professor of Medicine
Education
Ph.D., Pharmaceutical Sciences, University of Kentucky, Lexington, KentuckyPharm.D., State University of New York, Buffalo, New York
Research Description
Our laboratory is focused on improving treatment outcomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors through translational approaches. To accomplish this, we integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to identify altered pathways in cancer, the functional consequences of these alterations, and ways to directly target them in patients to improve clinical outcomes and survival. These efforts span in silico (publicly available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods.

There are several primary focuses of the laboratory:

1) How do tumor cells evade the immune system in cancer, and how can we target these mechanisms?

We have a strong interest in the intersection between new immunotherapies and tumor cell signaling pathways. We have identified several molecular pathways that are hijacked by tumor cells in order to suppress antigen presentation, which is required for effective immunologic elimination of tumor cells. Pharmacological inhibition of these pathways can restore antigen presentation, and potentiate anti-tumor immunity. However, the mechanisms by which tumor cells evade the immune system are largely unknown. The goal of this focus is to identify these mechanisms and validate approaches to inhibit them for the benefit of patients.

2) What molecular features or biomarkers can identify patients most likely to benefit from immunotherapy?

Immunotherapies have the potential to transform cancer therapy, but not all patients respond, and these drugs are incredibly costly and not without their toxicities (see #3). Thus, identifying patients most likely to benefit from immunotherapy early on, or a priori, could be incredibly valuable in triaging patients unlikely to respond to other therapies from which they are more likely to derive benefit. The discovery of molecular markers of response to immunotherapies is a major focus of the laboratory. We recently identified competence in class-II antigen presentation as a major predictor of outcome in patients treated with anti-PD-1 therapy, and are now exploring the functionality of MHC-II expression as a mediator of anti-tumor immunity.

3) What causes autoimmune-like toxicities in patients treated with immunotherapy?

As mentioned above, immunotherapies have the potential to cause rare, but severe toxicities, sometimes resulting in treatment-related mortality. Understanding the mechanisms behind immunotherapy-induced autoimmunity and the molecular features of patients who exhibit them is critical area of need. Through high level molecular profiling of peripheral blood, tumors, and immune-related adverse event-affected organs, we hope to uncover hints as to why some patients exhibit these toxicities, and try to model these toxicities in the laboratory.



Research Keywords
Translational cancer research with focuses on molecular therapeutics, onco-immunology and bioinformatics
Publications
Nixon MJ, Balko JM. Biomarkers for assessing the effectiveness of immunotherapy in breast cancer. Biomark Med [print-electronic]. 2018 Feb; 12(2): 97-100. PMID: 29338306, DOI: 10.2217/bmm-2017-0408, ISSN: 1752-0371.

Balko JM, Sosman JA. A Critical Need for Better Cancer Immunotherapy Models: Are Organotypic Tumor Spheroid Cultures the Answer?. Cancer Discov. 2018 Feb; 8(2): 143-5. PMID: 29431673, PII: 8/2/143, DOI: 10.1158/2159-8290.CD-17-1356, ISSN: 2159-8290.

Luo N, Nixon MJ, Gonzalez-Ericsson PI, Sanchez V, Opalenik SR, Li H, Zahnow CA, Nickels ML, Liu F, Tantawy MN, Sanders ME, Manning HC, Balko JM. DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer. Nat Commun. 2018 Jan 1/16/2018; 9(1): 248. PMID: 29339738, PMCID: PMC5770411, PII: 10.1038/s41467-017-02630-w, DOI: 10.1038/s41467-017-02630-w, ISSN: 2041-1723.

Croessmann S, Sheehan JH, Lee KM, Sliwoski GR, He J, Nagy RJ, Riddle DA, Mayer IA, Balko JM, Lanman RB, Miller V, Cantley LC, Meiler J, Arteaga CL. PIK3CA C2 domain deletions hyperactivate phosphoinositide 3-kinase (PI3K), generate oncogene dependence and are exquisitely sensitive to PI3Ka inhibitors. Clin. Cancer Res [print-electronic]. 2017 Dec 12/28/2017; PMID: 29284706, PII: 1078-0432.CCR-17-2141, DOI: 10.1158/1078-0432.CCR-17-2141, ISSN: 1078-0432.

Lee KM, Giltnane JM, Balko JM, Schwarz LJ, Guerrero-Zotano AL, Hutchinson KE, Nixon MJ, Estrada MV, Sánchez V, Sanders ME, Lee T, Gómez H, Lluch A, Pérez-Fidalgo JA, Wolf MM, Andrejeva G, Rathmell JC, Fesik SW, Arteaga CL. MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation. Cell Metab. 2017 Oct 10/3/2017; 26(4): 633-647.e7. PMID: 28978427, PII: S1550-4131(17)30560-0, DOI: 10.1016/j.cmet.2017.09.009, ISSN: 1932-7420.

Dushyanthen S, Teo ZL, Caramia F, Savas P, Mintoff CP, Virassamy B, Henderson MA, Luen SJ, Mansour M, Kershaw MH, Trapani JA, Neeson PJ, Salgado R, McArthur GA, Balko JM, Beavis PA, Darcy PK, Loi S. Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer. Nat Commun. 2017 Sep 9/19/2017; 8(1): 606. PMID: 28928458, PMCID: PMC5605577, PII: 10.1038/s41467-017-00728-9, DOI: 10.1038/s41467-017-00728-9, ISSN: 2041-1723.

Axelrod ML, Johnson DB, Balko JM. Emerging biomarkers for cancer immunotherapy in melanoma. Semin. Cancer Biol [print-electronic]. 2017 Sep 9/14/2017; PMID: 28917578, PII: S1044-579X(17)30121-9, DOI: 10.1016/j.semcancer.2017.09.004, ISSN: 1096-3650.

Williams MM, Vaught DB, Joly MM, Hicks DJ, Sanchez V, Owens P, Rahman B, Elion DL, Balko JM, Cook RS. ErbB3 drives mammary epithelial survival and differentiation during pregnancy and lactation. Breast Cancer Res. 2017 Sep 9/8/2017; 19(1): 105. PMID: 28886748, PMCID: PMC5591538, PII: 10.1186/s13058-017-0893-7, DOI: 10.1186/s13058-017-0893-7, ISSN: 1465-542X.

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.

Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O'Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors. Adv Anat Pathol [print-electronic]. 2017 Aug 8/2/2017; PMID: 28777143, DOI: 10.1097/PAP.0000000000000161, ISSN: 1533-4031.

Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, S Rinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O'Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research. Adv Anat Pathol [print-electronic]. 2017 Aug 8/2/2017; PMID: 28777142, DOI: 10.1097/PAP.0000000000000162, ISSN: 1533-4031.

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.

Song W, Hwang Y, Youngblood VM, Cook RS, Balko JM, Chen J, Brantley-Sieders DM. Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers. Oncogene [print-electronic]. 2017 Jun 6/5/2017; PMID: 28581527, PII: onc2017170, DOI: 10.1038/onc.2017.170, ISSN: 1476-5594.

Morales-Betanzos CA, Lee H, Gonzalez-Ericsson PI, Balko JM, Johnson DB, Zimmerman LJ, Liebler DC. Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma. Mol. Cell Proteomics [print-electronic]. 2017 May 5/25/2017; PMID: 28546465, PII: RA117.000037, DOI: 10.1074/mcp.RA117.000037, ISSN: 1535-9484.

Pinto JA, Rolfo C, Raez LE, Prado A, Araujo JM, Bravo L, Fajardo W, Morante ZD, Aguilar A, Neciosup SP, Mas LA, Bretel D, Balko JM, Gomez HL. In silico evaluation of DNA Damage Inducible Transcript 4 gene (DDIT4) as prognostic biomarker in several malignancies. Sci Rep. 2017 May 5/8/2017; 7(1): 1526. PMID: 28484222, PMCID: PMC5431475, PII: 10.1038/s41598-017-01207-3, DOI: 10.1038/s41598-017-01207-3, ISSN: 2045-2322.

Morales-Betanzos CA, Lee H, Gonzalez-Ericsson PI, Balko JM, Johnson DB, Zimmerman LJ, Liebler DC. WITHDRAWN: Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma. Mol. Cell Proteomics [print-electronic]. 2017 Apr 4/17/2017; PMID: 28416578, PII: M117.067942, DOI: 10.1074/mcp.M117.067942, ISSN: 1535-9484.

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.

Siska PJ, Johnpulle RAN, Zhou A, Bordeaux J, Kim JY, Dabbas B, Dakappagari N, Rathmell JC, Rathmell WK, Morgans AK, Balko JM, Johnson DB. Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling. Oncoimmunology. 2017; 6(4): e1305535. PMID: 28507813, PMCID: PMC5414873, PII: 1305535, DOI: 10.1080/2162402X.2017.1305535, ISSN: 2162-4011.

Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA, Anders RA, Sosman JA, Moslehi JJ. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N. Engl. J. Med. 2016 Nov 11/3/2016; 375(18): 1749-55. PMID: 27806233, PMCID: PMC5247797, DOI: 10.1056/NEJMoa1609214, ISSN: 1533-4406.

Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol [print-electronic]. 2016 Nov; 13(11): 674-90. PMID: 27184417, PII: nrclinonc.2016.66, DOI: 10.1038/nrclinonc.2016.66, ISSN: 1759-4782.

Johnson DB, Frampton GM, Rioth MJ, Yusko E, Xu Y, Guo X, Ennis RC, Fabrizio D, Chalmers ZR, Greenbowe J, Ali SM, Balasubramanian S, Sun JX, He Y, Frederick DT, Puzanov I, Balko JM, Cates JM, Ross JS, Sanders C, Robins H, Shyr Y, Miller VA, Stephens PJ, Sullivan RJ, Sosman JA, Lovly CM. Targeted Next Generation Sequencing Identifies Markers of Response to PD-1 Blockade. Cancer Immunol Res [print-electronic]. 2016 Nov; 4(11): 959-67. PMID: 27671167, PMCID: PMC5134329, PII: 2326-6066.CIR-16-0143, DOI: 10.1158/2326-6066.CIR-16-0143, ISSN: 2326-6074.

Johnson DB, Roszik J, Shoushtari AN, Eroglu Z, Balko JM, Higham C, Puzanov I, Patel SP, Sosman JA, Woodman SE. Comparative analysis of the GNAQ, GNA11, SF3B1, and EIF1AX driver mutations in melanoma and across the cancer spectrum [letter]. Pigment Cell Melanoma Res. 2016 Jul; 29(4): 470-3. PMID: 27089234, DOI: 10.1111/pcmr.12482, ISSN: 1755-148X.

Schwarz LJ, Balko JM. Maybe we don't know JAK?. Mol Cell Oncol. 2016 Jul; 3(4): e1192713. PMID: 27652332, PMCID: PMC4972112, PII: 1192713, DOI: 10.1080/23723556.2016.1192713.

Mayer IA, Abramson V, Formisano L, Balko JM, Estrada MV, Sanders M, Juric D, Solit D, Berger MF, Won H, Li Y, Cantley LC, Winer EP, Arteaga CL. A Phase Ib Study of Alpelisib (BYL719), a PI3Ka-specific Inhibitor, with Letrozole in ER+/HER2-Negative Metastatic Breast Cancer. Clin. Cancer Res [print-electronic]. 2016 Apr 4/28/2016; PMID: 27126994, PII: 1078-0432.CCR-16-0134, DOI: 10.1158/1078-0432.CCR-16-0134, ISSN: 1078-0432.

Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Dávila-González D, Wang K, Sánchez V, Dean PT, Combs SE, Hicks D, Pinto JA, Landis MD, Doimi FD, Yelensky R, Miller VA, Stephens PJ, Rimm DL, Gómez H, Chang JC, Sanders ME, Cook RS, Arteaga CL. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Sci Transl Med. 2016 Apr 4/13/2016; 8(334): 334ra53. PMID: 27075627, PII: 8/334/334ra53, DOI: 10.1126/scitranslmed.aad3001, ISSN: 1946-6242.

Amato KR, Wang S, Tan L, Hastings AK, Song W, Lovly CM, Meador CB, Ye F, Lu P, Balko JM, Colvin DC, Cates JM, Pao W, Gray NS, Chen J. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer. Cancer Res [print-electronic]. 2016 Jan 1/15/2016; 76(2): 305-18. PMID: 26744526, PMCID: PMC4715957, PII: 0008-5472.CAN-15-0717, DOI: 10.1158/0008-5472.CAN-15-0717, ISSN: 1538-7445.

Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB, Opalenik SR, Vilgelm AE, Feld E, Johnson AS, Greenplate AR, Sanders ME, Lovly CM, Frederick DT, Kelley MC, Richmond A, Irish JM, Shyr Y, Sullivan RJ, Puzanov I, Sosman JA, Balko JM. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat Commun. 2016; 7: 10582. PMID: 26822383, PMCID: PMC4740184, PII: ncomms10582, DOI: 10.1038/ncomms10582, ISSN: 2041-1723.

Pinto JA, Araujo J, Cardenas NK, Morante Z, Doimi F, Vidaurre T, Balko JM, Gomez HL. A prognostic signature based on three-genes expression in triple-negative breast tumours with residual disease. NPJ Genom Med. 2016; 1: 15015. PMID: 29263808, PMCID: PMC5685288, DOI: 10.1038/npjgenmed.2015.15, ISSN: 2056-7944.

Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clin. Cancer Res [print-electronic]. 2015 Oct 10/29/2015; PMID: 26515496, PII: 1078-0432.CCR-15-1125, DOI: 10.1158/1078-0432.CCR-15-1125, ISSN: 1078-0432.

Dillon LM, Bean JR, Yang W, Shee K, Symonds LK, Balko JM, McDonald WH, Liu S, Gonzalez-Angulo AM, Mills GB, Arteaga CL, Miller TW. P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT and MEK/ERK signaling in breast cancer. Oncogene [print-electronic]. 2015 Jul 7/23/2015; 34(30): 3968-76. PMID: 25284585, PMCID: PMC4387124, PII: onc2014328, DOI: 10.1038/onc.2014.328, ISSN: 1476-5594.

Bhola NE, Jansen VM, Bafna S, Giltnane JM, Balko JM, Estrada MV, Meszoely I, Mayer I, Abramson V, Ye F, Sanders M, Dugger TC, Allen EV, Arteaga CL. Kinome-wide functional screen identifies role of PLK1 in hormone-independent, ER-positive breast cancer. Cancer Res [print-electronic]. 2015 Jan 1/15/2015; 75(2): 405-14. PMID: 25480943, PMCID: PMC4297507, PII: 0008-5472.CAN-14-2475, DOI: 10.1158/0008-5472.CAN-14-2475, ISSN: 1538-7445.

Castaneda CA, Lopez-Ilasaca M, Pinto JA, Chirinos-Arias M, Doimi F, Neciosup SP, Rojas KI, Vidaurre T, Balko JM, Arteaga CL, Gomez HL. PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers. Hematol Oncol Stem Cell Ther [print-electronic]. 2014 Dec; 7(4): 142-8. PMID: 25467032, PII: S1658-3876(14)00084-3, DOI: 10.1016/j.hemonc.2014.09.007, ISSN: 1658-3876.

Baglia ML, Cai Q, Zheng Y, Wu J, Su Y, Ye F, Bao PP, Cai H, Zhao Z, Balko J, Zheng W, Lu W, Shu XO. Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome. Breast Cancer Res. Treat [print-electronic]. 2014 Nov; 148(1): 211-20. PMID: 25281216, PMCID: PMC4200532, DOI: 10.1007/s10549-014-3127-z, ISSN: 1573-7217.

Johnson DB, Dahlman KH, Knol J, Gilbert J, Puzanov I, Means-Powell J, Balko JM, Lovly CM, Murphy BA, Goff LW, Abramson VG, Crispens MA, Mayer IA, Berlin JD, Horn L, Keedy VL, Reddy NM, Arteaga CL, Sosman JA, Pao W. Enabling a genetically informed approach to cancer medicine: a retrospective evaluation of the impact of comprehensive tumor profiling using a targeted next-generation sequencing panel. Oncologist [print-electronic]. 2014 Jun; 19(6): 616-22. PMID: 24797823, PMCID: PMC4041676, PII: theoncologist.2014-0011, DOI: 10.1634/theoncologist.2014-0011, ISSN: 1549-490X.

Giltnane JM, Balko JM. Rationale for targeting the Ras/MAPK pathway in triple-negative breast cancer. Discov Med. 2014 May; 17(95): 275-83. PMID: 24882719, ISSN: 1944-7930.

Mayer IA, Abramson VG, Isakoff SJ, Forero A, Balko JM, Kuba MG, Sanders ME, Yap JT, Van den Abbeele AD, Li Y, Cantley LC, Winer E, Arteaga CL. Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J. Clin. Oncol [print-electronic]. 2014 Apr 4/20/2014; 32(12): 1202-9. PMID: 24663045, PMCID: PMC3986383, PII: JCO.2013.54.0518, DOI: 10.1200/JCO.2013.54.0518, ISSN: 1527-7755.

Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gómez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA. Emergence of constitutively active estrogen receptor-a mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin. Cancer Res [print-electronic]. 2014 Apr 4/1/2014; 20(7): 1757-67. PMID: 24398047, PMCID: PMC3998833, PII: 1078-0432.CCR-13-2332, DOI: 10.1158/1078-0432.CCR-13-2332, ISSN: 1078-0432.

Balko JM, Giltnane JM, Wang K, Schwarz LJ, Young CD, Cook RS, Owens P, Sanders ME, Kuba MG, Sánchez V, Kurupi R, Moore PD, Pinto JA, Doimi FD, Gómez H, Horiuchi D, Goga A, Lehmann BD, Bauer JA, Pietenpol JA, Ross JS, Palmer GA, Yelensky R, Cronin M, Miller VA, Stephens PJ, Arteaga CL. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov [print-electronic]. 2014 Feb; 4(2): 232-45. PMID: 24356096, PMCID: PMC3946308, PII: 2159-8290.CD-13-0286, DOI: 10.1158/2159-8290.CD-13-0286, ISSN: 2159-8290.

Balko JM, Schwarz LJ, Bhola NE, Kurupi R, Owens P, Miller TW, Gómez H, Cook RS, Arteaga CL. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Cancer Res [print-electronic]. 2013 Oct 10/15/2013; 73(20): 6346-58. PMID: 23966295, PMCID: PMC4090144, PII: 0008-5472.CAN-13-1385, DOI: 10.1158/0008-5472.CAN-13-1385, ISSN: 1538-7445.

Morrison MM, Hutchinson K, Williams MM, Stanford JC, Balko JM, Young C, Kuba MG, Sánchez V, Williams AJ, Hicks DJ, Arteaga CL, Prat A, Perou CM, Earp HS, Massarweh S, Cook RS. ErbB3 downregulation enhances luminal breast tumor response to antiestrogens. J. Clin. Invest [print-electronic]. 2013 Oct; 123(10): 4329-43. PMID: 23999432, PMCID: PMC3784526, PII: 66764, DOI: 10.1172/JCI66764, ISSN: 1558-8238.

Hanker AB, Pfefferle AD, Balko JM, Kuba MG, Young CD, Sánchez V, Sutton CR, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Aug 8/27/2013; 110(35): 14372-7. PMID: 23940356, PMCID: PMC3761610, PII: 1303204110, DOI: 10.1073/pnas.1303204110, ISSN: 1091-6490.

Young CD, Pfefferle AD, Owens P, Kuba MG, Rexer BN, Balko JM, Sánchez V, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL. Conditional loss of ErbB3 delays mammary gland hyperplasia induced by mutant PIK3CA without affecting mammary tumor latency, gene expression, or signaling. Cancer Res [print-electronic]. 2013 Jul 7/1/2013; 73(13): 4075-85. PMID: 23633485, PMCID: PMC3702683, PII: 0008-5472.CAN-12-4579, DOI: 10.1158/0008-5472.CAN-12-4579, ISSN: 1538-7445.

Dennison JB, Molina JR, Mitra S, González-Angulo AM, Balko JM, Kuba MG, Sanders ME, Pinto JA, Gómez HL, Arteaga CL, Brown RE, Mills GB. Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer. Clin. Cancer Res [print-electronic]. 2013 Jul 7/1/2013; 19(13): 3703-13. PMID: 23697991, PMCID: PMC3727144, PII: 1078-0432.CCR-13-0623, DOI: 10.1158/1078-0432.CCR-13-0623, ISSN: 1078-0432.

Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, Stanford J, Cook RS, Arteaga CL. TGF-ß inhibition enhances chemotherapy action against triple-negative breast cancer. J. Clin. Invest [print-electronic]. 2013 Mar; 123(3): 1348-58. PMID: 23391723, PMCID: PMC3582135, PII: 65416, DOI: 10.1172/JCI65416, ISSN: 1558-8238.

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.

Balko JM, Mayer IA, Sanders ME, Miller TW, Kuba MG, Meszoely IM, Wagle N, Garraway LA, Arteaga CL. Discordant cellular response to presurgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification. Mol. Cancer Ther [print-electronic]. 2012 Oct; 11(10): 2301-5. PMID: 22879364, PMCID: PMC3682668, PII: 1535-7163.MCT-12-0511, DOI: 10.1158/1535-7163.MCT-12-0511, ISSN: 1538-8514.

Balko JM, Cook RS, Vaught DB, Kuba MG, Miller TW, Bhola NE, Sanders ME, Granja-Ingram NM, Smith JJ, Meszoely IM, Salter J, Dowsett M, Stemke-Hale K, González-Angulo AM, Mills GB, Pinto JA, Gómez HL, Arteaga CL. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat. Med. 2012 Jul; 18(7): 1052-9. PMID: 22683778, PMCID: PMC3693569, PII: nm.2795, DOI: 10.1038/nm.2795, ISSN: 1546-170X.

Balko JM, Arteaga CL. Molecular signatures of lung cancer: defining new diagnostic and therapeutic paradigms. Mol Diagn Ther. 2012 Feb 2/1/2012; 16(1): 1-6. PMID: 22339590, DOI: 10.2165/11597430-000000000-00000, ISSN: 1179-2000.

Balko JM, Miller TW, Morrison MM, Hutchinson K, Young C, Rinehart C, Sánchez V, Jee D, Polyak K, Prat A, Perou CM, Arteaga CL, Cook RS. The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2012 Jan 1/3/2012; 109(1): 221-6. PMID: 22178756, PMCID: PMC3252958, PII: 1115802109, DOI: 10.1073/pnas.1115802109, ISSN: 1091-6490.

Bryant JL, Britson J, Balko JM, Willian M, Timmons R, Frolov A, Black EP. A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT. Br. J. Cancer [print-electronic]. 2012 Jan 1/3/2012; 106(1): 148-56. PMID: 22045191, PMCID: PMC3251842, PII: bjc2011465, DOI: 10.1038/bjc.2011.465, ISSN: 1532-1827.

Oh YT, Yue P, Zhou W, Balko JM, Black EP, Owonikoko TK, Khuri FR, Sun SY. Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation of ERK and JNK signaling. J. Biol. Chem [print-electronic]. 2012 Jan 1/2/2012; 287(1): 257-67. PMID: 22065586, PMCID: PMC3249076, PII: M111.304006, DOI: 10.1074/jbc.M111.304006, ISSN: 1083-351X.

Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J. Clin. Oncol [print-electronic]. 2011 Nov 11/20/2011; 29(33): 4452-61. PMID: 22010023, PMCID: PMC3221526, PII: JCO.2010.34.4879, DOI: 10.1200/JCO.2010.34.4879, ISSN: 1527-7755.

Fox EM, Miller TW, Balko JM, Kuba MG, Sánchez V, Smith RA, Liu S, González-Angulo AM, Mills GB, Ye F, Shyr Y, Manning HC, Buck E, Arteaga CL. A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res [print-electronic]. 2011 Nov 11/1/2011; 71(21): 6773-84. PMID: 21908557, PMCID: PMC3206206, PII: 0008-5472.CAN-11-1295, DOI: 10.1158/0008-5472.CAN-11-1295, ISSN: 1538-7445.

Miller TW, Balko JM, Fox EM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, Jiang A, Smith RA, Maira SM, Manning HC, González-Angulo AM, Mills GB, Higham C, Chanthaphaychith S, Kuba MG, Miller WR, Shyr Y, Arteaga CL. ERa-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov [print-electronic]. 2011 Sep; 1(4): 338-51. PMID: 22049316, PMCID: PMC3204388, PII: 2159-8290.CD-11-0101, DOI: 10.1158/2159-8290.CD-11-0101, ISSN: 2159-8290.

Balko JM, Arteaga CL. Dead-box or black-box: is DDX1 a potential biomarker in breast cancer?. Breast Cancer Res. Treat [print-electronic]. 2011 May; 127(1): 65-7. PMID: 20694745, DOI: 10.1007/s10549-010-1105-7, ISSN: 1573-7217.

Miller TW, Balko JM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, González-Angulo AM, Mills GB, Miller WR, Wu H, Shyr Y, Arteaga CL. A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. Clin. Cancer Res [print-electronic]. 2011 Apr 4/1/2011; 17(7): 2024-34. PMID: 21346144, PMCID: PMC3221728, PII: 1078-0432.CCR-10-2567, DOI: 10.1158/1078-0432.CCR-10-2567, ISSN: 1078-0432.

Ghosh R, Narasanna A, Wang SE, Liu S, Chakrabarty A, Balko JM, González-Angulo AM, Mills GB, Penuel E, Winslow J, Sperinde J, Dua R, Pidaparthi S, Mukherjee A, Leitzel K, Kostler WJ, Lipton A, Bates M, Arteaga CL. Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers. Cancer Res [print-electronic]. 2011 Mar 3/1/2011; 71(5): 1871-82. PMID: 21324925, PMCID: PMC3221734, PII: 0008-5472.CAN-10-1872, DOI: 10.1158/0008-5472.CAN-10-1872, ISSN: 1538-7445.

Balko JM, Black EP. Do the genes tell us the path of most resistance?. Cancer Biol. Ther. 2011 Jan 1/15/2011; 11(2): 213-5. PMID: 21263213, PII: 13922, DOI: 10.4161/cbt.11.2.13922, ISSN: 1555-8576.

Available Postdoctoral Position Details
Posted Position
2/27/2018

We are seeking a postdoctoral fellow to conduct multidisciplinary translational research in tumor immunology at the cutting-edge intersection of cancer biology and immunotherapy, bioinformatics, and clinical research. The ideal applicant will have a strong track record of graduate training in tumor immunology, with knowledge/proficiency in molecular and cancer biology, genomic screens, and/or basic immunology. Experience with ex vivo and in vivo murine model systems are preferred.

Our laboratory is focused on improving treatment outcomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors through translational approaches. To accomplish this, we integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to identify altered pathways in cancer, the functional consequences of these alterations, and ways to directly target them in patients to improve clinical outcomes and survival. These efforts span in silico (publicly available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods. There are several primary focuses of the laboratory:

1) How do tumor cells evade the immune system in cancer, and how can we target these mechanisms? We have a strong interest in the intersection between new immunotherapies and tumor cell signaling pathways. We have identified several molecular pathways that are hijacked by tumor cells in order to suppress antigen presentation, which is required for effective immunologic elimination of tumor cells. Pharmacological inhibition of these pathways can restore antigen presentation, and potentiate anti-tumor immunity. However, the mechanisms by which tumor cells evade the immune system are largely unknown. The goal of this focus is to identify these mechanisms and validate approaches to inhibit them for the benefit of patients.

2) What molecular features or biomarkers can identify patients most likely to benefit from immunotherapy? Immunotherapies have the potential to transform cancer therapy, but not all patients respond, and these drugs are incredibly costly and not without their toxicities (see #3). Thus, identifying patients most likely to benefit from immunotherapy early on, or a priori, could be incredibly valuable in triaging patients unlikely to respond to other therapies from which they are more likely to derive benefit. The discovery of molecular markers of response to immunotherapies is a major focus of the laboratory. We recently identified competence in class-II antigen presentation as a major predictor of outcome in patients treated with anti-PD-1 therapy, and are now exploring the functionality of MHC-II expression as a mediator of anti-tumor immunity.

3) What causes autoimmune-like toxicities in patients treated with immunotherapy? As mentioned above, immunotherapies have the potential to cause rare, but severe toxicities, sometimes resulting in treatment-related mortality. Understanding the mechanisms behind immunotherapy-induced autoimmunity and the molecular features of patients who exhibit them is critical area of need. Through high level molecular profiling of peripheral blood, tumors, and immune-related adverse event-affected organs, we hope to uncover hints as to why some patients exhibit these toxicities, and try to model these toxicities in the laboratory.

Fellows or trained research scientists with interest and skills in any or all of the areas are encouraged to contact the PI. The fellow will have the opportunity to:

1) Work with multidimensional data arising from exciting new human immunotherapy clinical trials being conducted by the PI to drive mechanistic studies elucidating mechanisms of sensitivity and resistance

2) Enjoy a well-funded and inter-disciplinary collaborative environment for large-scope projects in the molecular and immunotherapy translational space.

3) Drive dedicated self-directed projects in addition to collaborative projects. Applicants will be encouraged to work in a research space with a clear potential for patient impact, in a well-funded, publication-forward laboratory setting.

The trainee will be expected to work independently, and contribute creative outside-the-box ideas to the laboratory. Primarily (junior) postdoctoral fellows with a desire to work toward independent faculty academic positions or industry will be considered. Please forward your CV and a list of 3 references to justin.balko@vanderbilt.edu

2/24/2018

We are seeking a junior postdoctoral researcher with skills in molecular and cancer biology, translational animal models, and/or pathology to pursue novel strategies to treat a unique subtype of breast cancer called 'Inflammatory Breast Cancer'.  

Inflammatory breast cancer (IBC) is a rare special subtype of invasive breast cancer (1-5% of all breast cancers) characterized by a unique clinical presentation and molecular features. Patients presenting with IBC are often misdiagnosed due to the extreme swelling, bruising and redness of the breast, which is often a characteristic of other diseases or conditions, like mastitis. One of the key molecular features of IBC is its propensity to form tumor emboli (clusters of tumor cells) which preferentially invade into the local lymphatic system of the dermis. This feature is responsible in a large part for the clinical presentation of the disease, and also is likely related to its association with advanced clinical stage at diagnosis (almost always stage III-IV) because of local lymph node involvement. It is thought that overexpression of the tight-junction protein E-cadherin (and it’s cleavage by calpain) may be partially responsible for the formation of tumor emboli, but the reason behind the propensity of these emboli to invade and clog the lymphatic system is not known. One hypothesis for this feature is a unique response to cytokines in the microenvironment, such as IL6 and IL8, among others.

Aside from these clinical and molecular features, genomic studies have not elucidated substantial enrichments for genetic abnormalities unique to IBC. Furthermore, IBC can exist as all molecular subtypes of breast cancer, but most commonly triple-negative breast cancer (TNBC). For these reasons, IBC is often treated therapeutically as TNBC (except in rarer cases of HER2 or hormone receptor positivity). Chemotherapy is the mainstay of TNBC treatment, and response rates to chemotherapy are similar among IBC-TNBC and non-IBC-TNBC, although retrospective analyses demonstrate that IBC has a comparably poor prognosis, and is a unique molecular entity. As such, it becomes apparent that an improved understanding of the molecular features that dictate the unique clinical and pathological presentation of IBC will be paramount to designing appropriately targeted therapies to address this currently underserved molecular subtype of breast cancer.

The IBC Network Research Fellow will be supported by generous funding from the IBC Network Foundation and will work to develop murine and xenograft models of inflammatory breast cancer to test novel therapeutic strategies that can be translated for patient benefit.  Furthermore, through collaborations with Dana Farber Cancer Center and Genentech, the fellow will work with clinical human specimens of IBC to identify pathognomonic features of IBC that can be targeted and tested in the context of animal models and eventually clinical trials.

The fellow should have substantial evidence of productivity, creative thought, and independent thinking.  The ability to independently lead a project to completion is required, but the fellow will have substantial support form the PI and his laboratory.  Furthermore, a strong translational research community within the institution and laboratory can be leveraged to advance the project toward patient benefit.  

Please send a cover letter with a short write-up on interest specifically associated with this field and project, a current CV and list of three references to justin.balko@vanderbilt.edu.



1/3/2017

We are seeking a postdoctoral fellow or research scientist to conduct multidisciplinary translational research in computational biology/bioinformatics at the cutting-edge intersection of cancer biology and immunotherapy, bioinformatics, and clinical research.

The ideal applicant will have a strong computational biology background, with knowledge/proficiency in molecular and cancer biology, and/or immunology. Particular experience or expertise in TCR sequencing analysis, single-cell analysis, and neoantigen prediction are highly desired.  Fellows or trained research scientists with skills in any or all of the areas are encouraged to contact the PI.

The fellow/research scientist will have the opportunity to:

1) Work with multidimensional data arising from exciting new human immunotherapy clinical trials being conducted by the PI (TCR sequencing, whole-exome sequencing, RNAseq)

2) Collaborate on computational projects in the laboratory with other trainees (mouse, human, cell line studies) for additional publications

3) Enjoy a well-funded and inter-disciplinary collaborative environment for large-scope data-driven projects in the molecular and immunotherapy translational space.

4) Drive dedicated self-directed projects in addition to collaborative projects.

Applicants will be encouraged to work in a research space with a clear potential for patient impact, in a well-funded, publication-forward laboratory setting. The trainee will be expected to work independently, and contribute creative outside-the-box ideas to the laboratory. Both postdoctoral fellows and longer-term research scientists (with possibility of promotion within the laboratory) will be considered. 

Please forward your CV and a list of 3 references to justin.balko@vanderbilt.edu