Marsha Rosner, PhD

  • Charles B. Huggins Professor of Ben May Department of Cancer Research
  • Research and Scholarly Interests: Cancer, Breast, Exosomes, Macrophages, Metastasis, Oxidative Stress, Phosphorylation, Signal Transduction Pathways, Single Cell Analysis
  • Websites: Rosner Lab, Research Network Profile
  • Contact: m-rosner@uchicago.edu

Cancer is the second leading cause of death but, unlike heart disease, it has been a difficult disease to effectively understand or treat. The reason relates to the complexity and heterogeneity of the disease. Most tumors have complicated origins and are driven by rare mutations. Furthermore, different tissues have distinct cancers, individual tissues have multiple cancer subtypes, and tumors are composed of cells that are both genetically and phenotypically diverse. Thus, every tumor is unique and dynamic. The cause of lethality in most solid tumors such as breast cancer is the metastatic dissemination of tumor cells throughout the body. Metastasis is characterized by many distinct properties that are driven by changing stresses in the tumor microenvironment. Underlying all of these events are subcellular signaling pathways within tumor and environmental cells that are ultimately responsible for driving cells to a tumorigenic state.



The current focus of my laboratory is to understand fundamental signaling mechanisms leading to the generation of tumor cells and their progression to metastatic disease, particularly in triple-negative breast cancer that lacks targeted therapies. We use systems level approaches including activity-based proteomics, RNAseq, ChIPseq, and mass spectrometry as well as computational, molecular, biophysical, cellular and mouse model-based methodologies to identify and characterize key regulators of tumor growth and metastasis. As an additional tool, we have utilized a specific physiological suppressor of metastasis, Raf Kinase Inhibitory Protein (RKIP or PEBP1), and a downstream target of RKIP in cells, BACH1, to identify both molecular and cellular mediators of metastasis.



Our recent studies have shown that regulators of metastasis control multiple processes within the tumor cell microenvironment including metabolism, redox state, extracellular matrix, and recruitment and programming of tumor-associated macrophages. These factors also direct extracellular vesicles (exosomes) secreted by tumor cells to reprogram other cells in the body toward a pro-metastatic phenotype. Correlating omic-generated data from these studies with clinical data from cancer patients led to the identification of novel signaling modules that we used to build gene signatures that predict the metastatic potential of a tumor. More recently, our studies have led us to potential therapeutic treatments based on the concept of targeting key regulators of tumorigenesis, mimicking the action of metastasis suppressors such as RKIP or reprogramming signaling networks in cells to sensitize tumors to therapeutic agents.

Harvard University
Cambridge, MA
AB - Biochemistry
06/1972

Massachusetts Institute of Technology
Cambridge, MA
Ph.D. - Biochemistry
06/1978

Massachusetts Institute of Technology
Cambridge, MA
Postdoctoral Fellow - Biochemistry/MolBio
09/1981

Massachusetts Institute of Technology
Cambridge, MA
Instructor - Biochemistry/MolBio
09/1982

Interaction of tRNA with MEK2 in pancreatic cancer cells.
Wang X, Chow CR, Ebine K, Lee J, Rosner MR, Pan T, Munshi HG. Interaction of tRNA with MEK2 in pancreatic cancer cells. Sci Rep. 2016 06 15; 6:28260.
PMID: 27301426

Overexpression of initiator methionine tRNA leads to global reprogramming of tRNA expression and increased proliferation in human epithelial cells.
Pavon-Eternod M, Gomes S, Rosner MR, Pan T. Overexpression of initiator methionine tRNA leads to global reprogramming of tRNA expression and increased proliferation in human epithelial cells. RNA. 2013 Apr; 19(4):461-6.
PMID: 23431330

Anti-tumor effects of an engineered "killer" transfer RNA.
Zhou DH, Lee J, Frankenberger C, Geslain R, Rosner M, Pan T. Anti-tumor effects of an engineered "killer" transfer RNA. Biochem Biophys Res Commun. 2012 Oct 12; 427(1):148-53.
PMID: 22989754

Innate immune and chemically triggered oxidative stress modifies translational fidelity.
Netzer N, Goodenbour JM, David A, Dittmar KA, Jones RB, Schneider JR, Boone D, Eves EM, Rosner MR, Gibbs JS, Embry A, Dolan B, Das S, Hickman HD, Berglund P, Bennink JR, Yewdell JW, Pan T. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 2009 Nov 26; 462(7272):522-6.
PMID: 19940929

tRNA over-expression in breast cancer and functional consequences.
Pavon-Eternod M, Gomes S, Geslain R, Dai Q, Rosner MR, Pan T. tRNA over-expression in breast cancer and functional consequences. Nucleic Acids Res. 2009 Nov; 37(21):7268-80.
PMID: 19783824

Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration.
Shemon AN, Eves EM, Clark MC, Heil G, Granovsky A, Zeng L, Imamoto A, Koide S, Rosner MR. Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration. PLoS One. 2009 Jun 24; 4(6):e6028.
PMID: 19551145

RKIP regulates MAP kinase signaling in cells with defective B-Raf activity.
Zeng L, Ehrenreiter K, Menon J, Menard R, Kern F, Nakazawa Y, Bevilacqua E, Imamoto A, Baccarini M, Rosner MR. RKIP regulates MAP kinase signaling in cells with defective B-Raf activity. Cell Signal. 2013 May; 25(5):1156-65.
PMID: 23416466

Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target.
Zeng L, Imamoto A, Rosner MR. Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert Opin Ther Targets. 2008 Oct; 12(10):1275-87.
PMID: 18781826

Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1.
Hong J, Doebele RC, Lingen MW, Quilliam LA, Tang WJ, Rosner MR. Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1. J Biol Chem. 2007 Jul 06; 282(27):19781-7.
PMID: 17491018

Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism.
Shen Y, Joachimiak A, Rosner MR, Tang WJ. Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature. 2006 Oct 19; 443(7113):870-4.
PMID: 17051221

View All Publications

Fellow, American Association for the Advancement of Science (AAAS)
University of Chicago
2014 - 2014

Gerald N Wogan Prize Lecture, Massachusetts Institute of Technology
University of Chicago
2011 - 2011

Quantrell Award for Excellence in Undergraduate Teaching (Cancer Biology)
University of Chicago
2001 - 2001

Fellow, Institute of Medicine of Chicago
University of Chicago
1999 - pres

Quantrell Award for Excellence in Undergraduate Teaching, (Cell Biology)
University of Chicago
1991 - 1991

International Life Sciences Institute Research Foundation Award
MIT
1986 - 1986

American Cancer Society Postdoctoral Fellowship
MIT
1978 - 1980

Inst. National Research Service Award
MIT
1975 - 1977

Sloan Research Traineeship (Biophysics)
MIT
1973 - 1975

MIT Endowed Fellowship
MIT
1972 - 1972