Alexander S. BrodskyAssistant Professor of Pathology and Laboratory Medicine (Research)
Dr. Brodsky received his BA from the University of Pennsylvania where he worked with Dr. Ponzy Lu exploring DNA dynamics during electrophoresis. Dr. Brodsky received his PhD from MIT working with Dr. James R. Williamson where he developed a structural model of the HIV tat-TAR protein-RNA interaction using NMR spectroscopy.
Dr. Brodsky received postdoctoral training from Dr. Pamela A. Silver at the Dana-Farber Cancer Institute/Harvard Medical School where he discovered mechanisms of mRNA export. He was among the first to use chromatin immunoprecipitation combined with genomic tiling arrays to define the coupling of transcription and mRNA processing.
Dr. Brodsky joined the Pathology department in 2014.
27. Brown CW, Brodsky AS, Freiman RN. Notch3 Overexpression Promotes Anoikis Resistance in Epithelial Ovarian Cancer via Upregulation of COL4A2. Mol Cancer Res. 2014. doi: 10.1158/1541-7786.MCR-14-0334. PMID: 25169943.
26. Casella C, Miller DH, Lynch K, Brodsky AS*. Oxysterols synergize with statins by inhibiting SREBP-2 in ovarian cancer cells. Gynecologic oncology. 2014. doi: 10.1016/j.ygyno.2014.08.015. PubMed PMID: 25134999.
25. Ellermeier, C., Vang, S., Cleveland, K., Durand, W., Resnick, M. B.* and Brodsky, A. S.* (2014) “Prognostic MicroRNA Expression Signature from Examination of Colorectal Primary and Metastatic Tumors”, Anticancer Research, 34(8) 3957-67. (PMID: 25075017).
24. Brodsky, A. S.*, Fischer, A., Miller, D.H., Vang, S., MacLaughlan, S., Wu, H.-T., Yu, J., Steinhoff, M., Collins, C., Smither, J.S., and Brard, L. (2014) “Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease” PLoS One, 9(4) e94476 [Epub April 14, 2014] (PMID: 24732363, PMC3986100).
23. Vang, S., Wu, H.-T., Fischer, A., Miller, D.H., MacLauglan, S., Douglass, E., Steinhoff, M., Collins, C., Smith, P.J. Brard, L., Brodsky, A.S.* (2013) “Identification of Ovarian Cancer Metastatic miRNAs” PLoS One, 8(3) e58226 [Epub March 12, 2013] (PMID: 23554878, PMCID: PMC3595263).
22. Lu, S., Vincent, M. A., Mangray, S., Cleveland, K., Shillingford, N., Schorl, C., Brodsky, A.S., Resnick, M. B. (2012) “MicroRNA Profiling in Mucosal Biopsies of Eosinophilic Esophagitis Patients Pre and Post Treatment with Steroids and Relationship with mRNA Targets” PLoS One, 7(4) e40676 [Epub July 16, 2012] (PMID: 22815788, PMCID: PMC3398046).
21. Moore, R.G., Lange, T.S., Robinson, K., Kim K.K., Uzun, A, Horan, T.C., Kawar, N., Yano, N., Chu, S.R., Mao, Q., Brard, L., DePaepe, M.E., Padbury, J.F., Arnold, L.A., Brodsky, A., Shen, T.L., Singh, R.K. (2012) “Efficacy of a Non-hypercalcemic Vitamin-D2 Derived Anti-cancer Agent (MT19c) and Inhibition of Fatty Acid Synthesis in an Ovarian Cancer Xenograft Model” PLoS One; 7(4):e34443. Epub 2012 Apr 3. (PMID: 22509304, PMCID: PMC3317945.)
20. Miller D.H., Fischer A., Chu K.F., Burr R., Hillenmeyer S., Brard L., and Brodsky, A. S.* (2011) “T0901317 Inhibits Cisplatin Induced Apoptosis in Ovarian Cancer Cells” Int. J. Gynecol. Cancer [Epub Sep 5, 2011] (PMID 21921802, PMCID: PMC3203312).
19. Stuckey, A., Fischer, A., Miller, D.H., Hillenmeyer, S., Kim, K.K., Singh, R.K., Raphael, B. J., Brard, L., and Brodsky, .A.S.* (2011) “Integrated Genomics of Ovarian Xenograft Tumor Progression and Chemotherapy Response”. BMC Cancer, Jul 22; 11(1): 308 [Epub]. (PMID 21781307, PMCID: PMC3155912).
18. Wood, J., Hillenmeyer, S., Lawrence, C., Chang, C., Hosier, S., Lightfoot, W., Mukerjee, E., Jiang, N., Schorl, C., Brodsky, A.S., Neretti, N., and Helfand, S. L. (2010) “Chromatin Remodeling in the Aging Genome of Drosophila”, Aging Cell, 9(6) 971-8, Epub 2010 Oct 21 (PMID: 20961390, PMCID: PMC2980570).
17. Bronson, M. W., Hillenmeyer, S., Park, P. W., and Brodsky, A. S.* (2010) “Estrogen Coordinates Translation and Transcription Revealing a Role for NRSF in Human Breast Cancer Cells” Mol Endo, Jun;24(6):1120-35. Epub 2010 Apr 14 (PMID: 20392875, PMCID: PMC2875799).
16. Neretti, N., Wang, P.Y., Brodsky, A.S., Nyguyen, H.H., White, K.P., Rogina, B., and Helfand, S.L. (2009). Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage. Proc Natl Acad Sci U S A 106: 2277-2282 (PMID: 19164521).
14. Swinburne, I.A., Meyer, C.A., Liu, X.S., Silver, P.A., and Brodsky, A.S.* (2006). Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription. Genome Res 16: 912-921 (PMID: 16769980).
13. Gama-Carvalho, M., Barbosa-Morais, N.L., Brodsky, A.S., Silver, P.A., and Carmo-Fonseca, M. (2006). Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors. Genome Biol 7: R113 (PMID: 17137510).
11. Carroll, J.S., Liu, X.S., Brodsky, A.S., Li, W., Meyer, C.A., Szary, A.J., Eeckhoute, J., Shao, W., Hestermann, E.V., Geistlinger, T.R., Fox, E.A., Silver, P.A., and Brown, M. (2005). Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 122: 33-43 (PMID: 16009131).
10. Brodsky, A.S.*, Meyer, C.A., Swinburne, I.A., Hall, G., Keenan, B.J., Liu, X.S., Fox, E.A., and Silver, P.A. (2005). Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells. Genome Biol 6: R64 (PMID: 16086846).
9. Brodsky, A.S., Johnston, A.P., Trau, M., and Silver, P.A. (2003). Analysis of RNA-protein interactions by flow cytometry. Curr Opin Mol Ther 5: 235-240 (PMID: 12870432).
7. Brodsky, A.S., and Silver, P.A. (2002). Identifying proteins that affect mRNA localization in living cells. Methods 26: 151-155 (PMID: 12054891).
6. Brodsky, A.S.*, and Silver, P.A. (2002). A microbead-based system for identifying and characterizing RNA-protein interactions by flow cytometry. Mol Cell Proteomics 1: 922-929 (PMID: 12543929).
8. Dayie, K.T., Brodsky, A.S., and Williamson, J.R. (2002). Base flexibility in HIV-2 TAR RNA mapped by solution (15)N, (13)C NMR relaxation. J Mol Biol 317: 263-278 (PMID: 11902842).
5. Hennig, M., Williamson, J.R., Brodsky, A.S., and Battiste, J.L. (2001). Recent advances in RNA structure determination by NMR. Curr Protoc Nucleic Acid Chem Chapter 7: Unit 7.7 (PMID: 18428875).
4. Brodsky, A.S., and Silver, P.A. (2000). Pre-mRNA processing factors are required for nuclear export. RNA 6: 1737-1749 (PMID: 11142374).
3. Brodsky, A.S., and Silver, P.A. (1999). Nuclear transport HEATs up. Nat Cell Biol 1: E66-67 (PMID: 10559913).
2. Brodsky, A.S., Erlacher, H.A., and Williamson, J.R. (1998). NMR evidence for a base triple in the HIV-2 TAR C-G.C+ mutant-argininamide complex. Nucleic Acids Res 26: 1991-1995 (PMID: 9518494).
1. Brodsky, A.S., and Williamson, J.R. (1997). Solution structure of the HIV-2 TAR-argininamide complex. J Mol Biol 267: 624-639 (PMID: 9126842).
Our goal is to understand which tumors respond to chemotherapy and which do not. We have compared primary and metastatic tumors to identify which tumors are the most aggressive and resistant to treatment. We have discovered new proteins and microRNA biomarkers strongly associated with chemotherapy response and survival. In the laboratory, we have discovered a new approach to enhance the anti-tumor activity of statins and are investigating how statins could be used to prevent tumor relapse.
My laboratory uses an variety of approaches to understand tumor relapse and chemosensitivity. We examine tumors from patients and mouse models as well as in vitro models to develop biomarkers and new drug combinations.
We have identified a key feedback loop important for the regulation of cholesterol that mediates ovarian and breast cancer growth and survival. We are investigating the mechanisms of this regulation and translating our discoveries to develop novel anti-tumor drug combinations.
We are exploring the role of RNA processing in response to hormones such as estrogen in breast cancer. We are identifying novel components mediating hormone control of cancer cells that are regulated post-transcriptionally.
We are characterizing the key differences between ovarian primary and metastatic tumors. This has led to the discovery of new microRNAs and pathways important for ovarian cancer cell survival and response to chemotherapy.
Mary Kay Foundation (PI)
Ellison Medical Foundation (PI) (completed)
Susan G. Komen Breast Cancer Foundation (co-PI) (completed)
ARRA Supplement: Biocurrents Research Center (PI subcontract) (completed)
DOD/CDMRP Breast Cancer Synergy Award(Completed)
NHGRI K22 Genome Scholar Career Development Award (Completed)