Milan Radovich, PhD
Assistant Professor of Surgery
Specialty: General Surgery
Dr. Milan Radovich is an assistant professor in the Department of Surgery at the Indiana University School of Medicine. He is also a member of the IU Simon Cancer Center, IU Center for Computational Biology and Bioinformatics, and the Indiana Institute for Personalized Medicine. His research focuses on the use of next-generation sequencing in translational oncology. In particular, his laboratory focuses on the use of next-generation sequencing for drug development, pharmacogenomics, and understanding mutational causes of cancer. In addition, a major focus of his work is integration of next-generation sequencing into cancer clinical trials with a special focus on using genomics for precision medicine.
Basic Research Interests:
My laboratory is focused on the use of next-generation sequencing technology in translational oncology. In particular, we are using this technology to identify novel drug targets to better treat triple-negative breast cancer, inflammatory breast cancer, and thymic malignancies. We are also using the technology to identify novel mutations that can help explain the causation of these diseases. Our work is very integrated into the clinical enterprise of the Indiana University Simon Cancer Center, and actively works with a team of clinicians to recruit patient samples and to apply findings to correlative studies within clinical trials. Current research revolves around three main projects:
- Project 1. Triple-negative breast cancer and the normal breast: We have recently sequenced and analyzed the entire transcriptomes of triple-negative breast cancers and normal breast tissues. Our normal controls were derived from microdissected ductal epithelium collected from the unique resource of the Susan G. Komen Tissue Bank at the IU Simon Cancer Center. This data has revealed transcriptional differences that have leant understanding into why previous targeted therapies in triple-negative breast cancer have failed in clinical trial, and also has identified new targets that are now active in drug development. We are also identifying novel mutations that are lending clues into the possible causation and chemotherapeutic sensitivity of triple-negative breast cancers.
- Project 2. Inflammatory Breast Cancer: Our newest project is studying the transcriptomes of inflammatory breast cancers (IBC), a rare and aggressive breast cancer that carries a poor prognosis. This disease is characterized by the dissemination of tumor cells into the subdermal lymphatics leading to an inflammatory response. In partnership with the IBC Research Foundation and NYU, we are using next-generation RNA sequencing to understand the key gene expression perturbations and mutational events that comprises this disease. In addition, we are leveraging our expertise in the transcriptomics of the normal breast to understand the key genes that differentiates IBC from normal breast tissue.
- Project 3. Thymic Malignancies: Thymomas and thymic carcinomas are rare diseases with only ~500 cases in the US per year. The Indiana University Simon Cancer Center is a world leader in thymic malignancies and cares for a large proportion of affected patients. Using the unique tissue resources available at our institution for this disease, we have recently completed the RNA-sequencing of a cohort of thymic malignancies. Preliminary data has demonstrated that gene expression profiling can perfectly delineate the WHO subtypes for thymomas, which has traditionally been difficult to assess using standard histopathologic features. Further, preliminary data is identifying recurrent mutations in key driver genes that may lead to understanding the causation and possible treatment of this rare disease.
Using data derived from these projects, we are actively translating these findings into further downstream pre-clinical investigations and clinical applications including: further elucidation of the intrinsic tumor biology, development of diagnostics, and development of novel therapeutics.
- Zhang P, Schwartz O, Pantelic M, Li G, Knazze Q, Nobile C, Radovich M, He J, Hong SC, Klena J, Chen T. DC-SIGN (CD209) recognition of Neisseria gonorrhoeae is circumvented by lipooligosaccharide variation. J Leukoc Biol. 2006 Apr;79(4):731-8. Epub 2006 Feb 3. PubMed PMID: 16461738.
- Schneider BP, Radovich M, Sledge GW, Robarge JD, Li L, Storniolo AM, Lemler S, Nguyen AT, Hancock BA, Stout M, Skaar T, Flockhart DA. Association of polymorphisms of angiogenesis genes with breast cancer. Breast Cancer Res Treat. 2008 Sep;111(1):157-63. Epub 2007 Sep 20. PubMed PMID: 17891484.
- Schneider BP, Radovich M, Flockhart DA, Carpenter JS, Li L, Robarge JD, Storniolo AM, Hancock BA, Skaar TC, Sledge GW. Exploratory study evaluating the association of polymorphisms of angiogenesis genes with hot flashes. Breast Cancer Res Treat. 2009 Aug;116(3):543-9. Epub 2008 Sep 11. PubMed PMID: 18785001.
- Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD; ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008 Oct 1;26(28):4672-8. Erratum in: J Clin Oncol. 2009 Jun 20;27(18):3070. PubMed PMID: 18824714; PubMed Central PMCID: PMC2653128.
- Miao J, Jin Y, Marunde RL, Kim S, Quinney S, Radovich M, Li L, Hall SD. Association of genotypes of the CYP3A cluster with midazolam disposition in vivo. Pharmacogenomics J. 2009 Oct;9(5):319-26. Epub 2009 Jun 9. PubMed PMID: 19506580; PubMed Central PMCID: PMC2749890.
- Wang X, Wang K, Radovich M, Wang Y, Wang G, Feng W, Sanford JR, Liu Y. Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing. BMC Genomics. 2009 Jul 7;10 Suppl 1:S4. PubMed PMID: 19594881; PubMed Central PMCID: PMC2709265.
- Schneider BP, Radovich M, Miller KD. The role of vascular endothelial growth factor genetic variability in cancer. Clin Cancer Res. 2009 Sep 1;15(17):5297-302. Epub 2009 Aug 25. PubMed PMID: 19706811.
- Radovich M, Hancock BA, Kassem N, Mi D, Skaar TC, Schneider BP. Resequencing of the vascular endothelial growth factor promoter reveals haplotype structure and functional diversity. Angiogenesis. 2010 Sep;13(3):211-8. Epub 2010 Jun 16.PubMed PMID: 20552269.
- Wessels AM, Flockhart DA, Carpenter JS, Radovich M, Li L, Miller KD, Sledge GW, Storniolo AM, Otte JL, Lemler SM, Schneider BP. Cytochrome P450 polymorphisms and their relationship with premature ovarian failure in premenopausal women with breast cancer receiving doxorubicin and cyclophosphamide. Breast J. 2011 Sep-Oct;17(5):536-8. doi: 10.1111/j.1524-4741.2011.01144.x. Epub 2011 Aug 9. PubMed PMID: 21827565.
- Slee R, Steiner CM, Herbert B-S, Vance GH, Hickey RJ, Schwarz T, Christan S, Radovich M, Schneider BP, Schindelhauer D, Grimes BR. Cancer associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. Oncogene. 2011 Nov 14. doi: 10.1038/onc.2011.502. [Epub ahead of print] PubMed PMID: 22081068.
- Sakarya O, Breu H, Radovich M, Chen Y, Wang YN, Barbacioru C, Utiramerur S, Whitley PP, Brockman JP, Vatta P, Zhang Z, Popescu L, Muller MW, Kudlingar V, Garg N, Li C-Y, Kong BS, Bodeau JP, Nutter RC, Gu J, Bramlett KS, Ichikawa JK, Hyland FC, Siddiqui AS. RNA-Seq Mapping and Detection of Gene Fusions with a Suffix Array Algorithm. PLoS Comput Biol. 2012 Apr;8(4):e1002464. Epub 2012 Apr 5. PubMed PMID: 22496636; PubMed Central PMCID: PMC3320572.
- Radovich, M. Next Generation Sequencing in Breast Cancer: Translational Science and Clinical Integration. Pharmacogenomics. 2012 Apr;13(6):637-9. PubMed PMID:22515604.
- Schneider BP, Gray R, Radovich M, Shen F, Vance GH, Li L, Jiang G, Miller KD, Gralow J, Dickler MN, Cobleigh M, Perez EA, Shenkier TN, Nielsen KV, Müller S, Thor AD, Sledge GW, Sparano JA, Davidson NE, Badve S. Prognostic and predictive value of tumor VEGF gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial. Clin Cancer Res. 2013 Jan 22. [Epub ahead of print] PubMed PMID: 23340303.
- Juan L, Wang G, Radovich M, Schneider BP, Clare SE, Wang Y, Liu Y. Potential roles of microRNAs in regulating long intergenic noncoding RNAs. BMC Med Genomics. 2013;6 Suppl 1:S7. doi:10.1186/1755-8794-6-S1-S7. Epub 2013 Jan 23. PubMed PMID: 23369519; PubMed Central PMCID: PMC3552696.