Marsha Rosner, PhD

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.

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

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

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

Harvard University
Cambridge, MA
AB - Biochemistry
1972

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses.
Nguyen LC, Yang D, Nicolaescu V, Best TJ, Gula H, Saxena D, Gabbard JD, Chen SN, Ohtsuki T, Friesen JB, Drayman N, Mohamed A, Dann C, Silva D, Robinson-Mailman L, Valdespino A, Stock L, Suárez E, Jones KA, Azizi SA, Demarco JK, Severson WE, Anderson CD, Millis JM, Dickinson BC, Tay S, Oakes SA, Pauli GF, Palmer KE. Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses. Sci Adv. 2022 Feb 25; 8(8):eabi6110.
PMID: 35050692

Harnessing RKIP to Combat Heart Disease and Cancer.
Lorenz K, Rosner MR. Harnessing RKIP to Combat Heart Disease and Cancer. Cancers (Basel). 2022 Feb 09; 14(4).
PMID: 35205615

New strategies for targeting kinase networks in cancer.
Yesilkanal AE, Johnson GL, Ramos AF, Rosner MR. New strategies for targeting kinase networks in cancer. J Biol Chem. 2021 10; 297(4):101128.
PMID: 34461089

Tumor Extracellular Vesicles Regulate Macrophage-Driven Metastasis through CCL5.
Rabe DC, Walker ND, Rustandy FD, Wallace J, Lee J, Stott SL, Rosner MR. Tumor Extracellular Vesicles Regulate Macrophage-Driven Metastasis through CCL5. Cancers (Basel). 2021 Jul 10; 13(14).
PMID: 34298673

Limited inhibition of multiple nodes in a driver network blocks metastasis.
Yesilkanal AE, Yang D, Valdespino A, Tiwari P, Sabino AU, Nguyen LC, Lee J, Xie XH, Sun S, Dann C, Robinson-Mailman L, Steinberg E, Stuhlmiller T, Frankenberger C, Goldsmith E, Johnson GL, Ramos AF, Rosner MR. Limited inhibition of multiple nodes in a driver network blocks metastasis. Elife. 2021 05 11; 10.
PMID: 33973518

Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response.
Nguyen LC, Yang D, Nicolaescu V, Best TJ, Ohtsuki T, Chen SN, Friesen JB, Drayman N, Mohamed A, Dann C, Silva D, Gula H, Jones KA, Millis JM, Dickinson BC, Tay S, Oakes SA, Pauli GF, Meltzer DO, Randall G, Rosner MR. Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response. bioRxiv. 2021 Mar 10.
PMID: 33758843

Observation and Control of Gene Expression Noise: Barrier Crossing Analogies Between Drug Resistance and Metastasis.
Guinn MT, Wan Y, Levovitz S, Yang D, Rosner MR, Balázsi G. Observation and Control of Gene Expression Noise: Barrier Crossing Analogies Between Drug Resistance and Metastasis. Front Genet. 2020; 11:586726.
PMID: 33193723

Teaching Intersectionality of Sexual Orientation, Gender Identity, and Race/Ethnicity in a Health Disparities Course.
Bi S, Vela MB, Nathan AG, Gunter KE, Cook SC, López FY, Nocon RS, Chin MH. Teaching Intersectionality of Sexual Orientation, Gender Identity, and Race/Ethnicity in a Health Disparities Course. MedEdPORTAL. 2020 07 31; 16:10970.
PMID: 21602892

Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer.
Tiwari P, Blank A, Cui C, Schoenfelt KQ, Zhou G, Xu Y, Khramtsova G, Olopade F, Shah AM, Khan SA, Rosner MR, Becker L. Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer. J Exp Med. 2019 06 03; 216(6):1345-1358.
PMID: 31053611

Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism.
Lee J, Yesilkanal AE, Wynne JP, Frankenberger C, Liu J, Yan J, Elbaz M, Rabe DC, Rustandy FD, Tiwari P, Grossman EA, Hart PC, Kang C, Sanderson SM, Andrade J, Nomura DK, Bonini MG, Locasale JW, Rosner MR. Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism. Nature. 2019 04; 568(7751):254-258.
PMID: 30842661

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