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Suzanne Ostrand-Rosenberg

Prof. Biology, Robert+Jane Meyerhoff Chair

Biological Sciences
Biological Sciences Bldg, Room 221
Phone
410-455-2237
410-455-2237
srosenbe@umbc.edu
Education
Ph D, California Institute of Technology (1975)
Other, Barnard College, Columbia University (1970)
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About

I have more than 37 years of experience as the PI of a laboratory studying the immune system’s response to malignancies. Throughout this period my lab’s long-term goal has been to manipulate an individual's immune response to reject cancer cells. In the 1990’s we were instrumental in demonstrating that CD4+ T helper lymphocytes are essential for immune-mediated tumor rejection. Recently, we were among the first labs to appreciate that myeloid-derived suppressor cells (MDSC) are highly immune suppressive cells present in virtually all cancer patients, and are a significant obstacle to active cancer immunotherapies. Our work demonstrating that MDSC are induced by a variety of pro-inflammatory mediators was described in a Science Magazine “News Focus” article and is the basis for the concept that chronic inflammation increases cancer risk and cancer progression by inducing MDSC which inhibit anti-tumor immunity. Our lab was also the first to demonstrate that macrophages, the other major pro-tumor myeloid cell population that infiltrates solid tumors, undergo cross-talk with MDSC which enhances the pro-tumor activity of both cell populations. Studies to date have identified a variety of physiological conditions and molecules that drive the accumulation and suppressive potency of MDSC and macrophages. However, neutralization of these cells has been unsuccessful because of the multiple pro-inflammatory mediators that drive their accumulation and function. Our preliminary studies, which are the basis for this application, demonstrate that the ubiquitously expressed alarmin, HMGB1, and the pro-inflammatory mediator S100A8/A9, are master regulators that activate MDSC by binding to the Receptor for Advanced Glycation Endproducts (RAGE). These observations led us to hypothesize that pro-tumor MDSC and TAMs may be neutralized by targeting RAGE, HMGB1, and S100A8/A9. If our hypothesis is correct, then our studies will provide a global and universal strategy for eliminating the suppressive activity of these myeloid cell populations and provide a more favorable environment for immunotherapy in cancer patients.

Research Interests

Tumor/cancer immunology; tumor-induced immune suppression; cancer vaccine development

Teaching Interests

Immunology Cell Biology Cancer Biology

Selected Classes
Spring 2014 BIOL 397 – Ethics and Integrity in Scientific Research
Contracts, Fellowships, Grants, and Sponsored Research

Ostrand-Rosenberg, Suzanne (Principal) Darryl, Carter (Supporting) A novel BiTE as an immunotherapy drug for the treatment of cancer Grant (Funded) Sponsored by TEDCO MII program (Sep 28, 2015 – Jun 28, 2016)

Ostrand-Rosenberg, Suzanne (Co-Principal) Fulton, Amy (Principal) Targeting the COX-2 Pathway to Reduce Breast Cancer Mortality Grant (Funded) Sponsored by VA (UMB subcontract to UMBC) (Jun 1, 2015 – May 30, 2019)

Ostrand-Rosenberg, Suzanne (Principal) A novel recombinant molecule that simultaneously inhibits PDL1/PD1-mediated immune suppression and boosts the activation of tumor-reactive T cells. Cooperative Agreement (Funded) Sponsored by MedImmune, Inc. (Sep 3, 2014 – Jun 2, 2016)

Ostrand-Rosenberg, Suzanne (Principal) Does G-CSF promote maternal-fetal tolerance by inducing immune suppressive myeloid-derived suppresser cells (MDSC)? Cooperative Agreement (Funded) Sponsored by Nora Therapeutics (Apr 23, 2014 – Apr 22, 2015)

Ostrand-Rosenberg, Suzanne (Principal) Catherine, Fenselau (Principal) David, Fushman (Principal) Ubiquitinated Proteins in Exosomes of Immune Suppressive Myeloid Cells. Grant (Funded) Sponsored by NIH (Feb 1, 2014 – Jan 31, 2018)

Ostrand-Rosenberg, Suzanne (Supporting) Eduardo, Davila (Principal) Amplifying TCR Responses and Resisting MDSC-mediated Suppression via MyD88 Signaling in T cells Grant (Currently Under Review) Sponsored by NIH

Ostrand-Rosenberg, Suzanne

Intellectual Contributions

Frontline Science: Myeloid-derived suppressor cells (MDSCs) facilitate maternal-fetal tolerance in mice vol. epub Society of Leukocyte Biology Journal of Leukocyte Biology

Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes vol. 5 eLIFE

Myeloid-derived suppressor cells. Encyclopedia of Immunobiology 1 vol. 4 511-525 Oxford Academic Press Elsevier

Myeloid-Derived Suppressor Cell Survival and Function Are Regulated by the Transcription Factor Nrf2 vol. 196 3470-3478 American Association of Immunologists Journal of Immunology

High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy vol. 100 463-470 Society of Leukocyte Biology Journal of Leukocyte Biology

Tolerance and immune suppression in the tumor microenvironment vol. 299 23-29 Elsevier Cellular Immunology

Myeloid-derived suppressor cells: critical cells driving immune suppression in the tumor microenvironment Advances in Cancer Research vol. 128 95-139 Advances in Cancer Research

Novel strategies for inhibiting PD-1 pathway-mediated immune suppression while simultaneously delivering activating signals to tumor-reactive T cells vol. 64 1287-1293 Springer, Cancer Immunology, Immunotherapy

Top-down analysis of low mass proteins in exosomes shed by murine myeloid-derived suppressor cells. vol. 378 264-269 International Journal of Mass Spectrometry

Ubiquitinated proteins in exosomes secreted by myeloid-derived suppressor cells vol. 13 5965-5972 Journal of Proteome Research

The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity vol. 193 3835-3841 American Association of Immunologists The Journal of Immunology

Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors vol. 96 1109-1118 Society of Leukocyte Biology Journal of Leukocyte Biology

vol. 13 836-843 American Chemical Society J. Proteome Research

Tumor-Induced Immune Suppression - Mechanisms and Therapeutic Reversal 185-212 NY, Heidelberg,Dordrecht, London Springer

vol. 191 2829-2836 J. of Immunology

vol. 62 1663-1673 NY, Heidelberg,Dordrecht, London Springer

vol. 62 1-2 Berlin-Heidelberg Springer-Verlag

Tumor Immunoenvironment NY, Heidelberg,Dordrecht, London Springer

Soluble CD80 protein delays tumor growth and promotes tumor infiltrating lymphocytes American Association of Cancer Research Cancer Immunology Research

Encyclopedia of Immunology Elsevier

Intellectual Property

Patent Recombinant Bi-specific Polypeptides for Coordinately Activating Tumor-reative T Cells and Neutralizing Immune Suppression 62092506 (application number) Application: Dec 16, 2014

Patent Solulble CD80 as a therapeutic to reverse immune suppression in cancer patients 13/660,037 Application: Oct 25, 2012 Approved: Dec 5, 2014

Presentations

(Author & Presenter) Cold Spring Harbor Symposium on Tumor Immunology & Immunotherapy Lecture Immune suppression in obesity and tumor progression Cold Spring Harbor Suzhou, China

(Author & Presenter) Progress in Vaccination Against Cancer , 17th edition Keynote/Plenary Address The good, the bad, and the in-between: immune suppression, obesity, and tumor progression PIVAC (Progress in Vaccination Against Cancer) Loutraki, Greece

(Author & Presenter) 47th Annual meeting of the German Society for Immunology Lecture Obesity, immune suppression, & tumor progression German Society for Immuno9logy Erlangen, Germany

(Author & Presenter) 22nd Congress of the European Hematology Association Lecture Myeloid-derived suppressor cells (MDSC): Critical cells that link obesity to cancer and drive immune suppression in the tumor microenvironment European Hematology Association Madrid, Spain

(Author & Presenter) American Association of Immunologists annual meeting 2017 Keynote/Plenary Address The good, the bad, and the in-between: immune suppression, obesity, and tumor progression American Association of Immunologists Washington, DC

(Author & Presenter) II congreso Internacional de Immuno-Oncologia Keynote/Plenary Address Understanding and neutralizing cancer-induced immune suppression to promote antitumor immunity Mexican National Cancer Institute, Sonora Cancer Research Center, Mexican Society of Medical Oncology Ciudad Obregon, Sonora, Mexico

(Author & Presenter) Rutgers University Seminar Myeloid-derived Suppressor Cells (MDSC): Bad If You Have Cancer; Good If You’re Pregnant Rutgers University Rutgers University

(Author & Presenter) Regulatory Myeloid Suppressor Cells Lecture MDSC: Multi-talented immune suppressive cells that mediate both detrimental & beneficial effects Wistar Institute Philadelphia, PA

(Author & Presenter) Immunology, Membrane Dynamics, and Beyond: A Symposium in Honor of Professor Michael Edidin Lecture Immune suppression: bad if you have a tumor, but good if you’re pregnant Johns Hopkins University Baltimore, MD

(Author & Presenter) Tumor Immunology Meets Oncology (TIMO) Lecture Enhancing antitumor immunity & neutralization of immune suppression in the tumor microenvironment Martin Luther University, Halle-Wittenberg, Germany University Hospital Halle

(Author & Presenter) TEDCO Oral Presentation A novel BiTE as an immunotherapy drug for the treatment of cancer TEDCO Columbia, MD

(Author & Presenter) IASLC 16th Annual Targeted Therapies of Lung Cancer Conference Lecture Other Immune Suppressive Mechanisms & Their Potential Therapies International Association for the Study of Lung Cancer Santa Monica, CA

(Author & Presenter) Joint scientific meeting MedImmune and UMD Lecture A novel recombinant molecule that simultaneously inhibits PDL1/PD1-mediated immune suppression and boosts the activation of tumor-reactive T cells MedImmune/UMD Gaithersberg, MD

(Author & Presenter) 3rd Annual Summit on Thoracic Malignancies & Head & Neck Cancers Lecture Novel, non-antibody approaches for blocking the PD-1 immune suppressive pathway and enhancing antitumor immunity International Association for the study of lung cancer San Juan, Puerto Rico

Seminar Novel approaches for blocking the PD-1 immune suppressive pathway and enhancing antitumor immunity University of Rochester Rochester, NY

(Author & Presenter) Lecture Tumor-induced immune suppression: the last obstacle (or just another bump in the road) to global success of cancer immunotherapies? University of Utah Salt Lake City, UT

(Author & Presenter) Lecture Myeloid cells as an obstacle to cancer immunotherapy Karolinska Institutet for Cancer Research Stockholm, Sweden

(Author & Presenter) Cancer Immunotherapy & Immunomonitoring Conference (CITIM) Lecture how to survive inf you are a myeloid-derived suppressor cell (MDSC) CITIM Society Ljubljana, Slovenia

Look Ahead Symposium Keynote/Plenary Address The immune system vs. cancer: winners, losers, and complications UMBC UMBC

(Author & Presenter) Seminar Novel approaches for blocking the PD1 immune suppressive pathway and enhancing antitumor immunity Wistar Institute Philadelphia, PA

(Author & Presenter) MedImmune Lecture Novel Strategies for Neutralizing PD-1 Pathway-mediated Immune Suppression in Cancer MedImmune, Inc. Gaitherburg, MD

(Author & Presenter) Baylor College of Medicine Seminar Inflammation, Alarmins,and Immune Suppression in the Tumor Microenvironment: It’s the RAGE Baylor College of Medicine Dallas, TX

UMBC President's Council Oral Presentation Activating a Patient’s Immune System to Destroy Cancer Cells UMBC United States

(Author & Presenter) Loyola University Cancer Immunotherapy Retreat Keynote/Plenary Address Inflammation and Immune Suppression in the Tumor Microenvironment Loyola University of Chicago Loyola University, Chicago

(Author & Presenter) Univ. of Michigan Immunology Seminar Series Seminar Inflammation, Alarmins,and Immune Suppression in the Tumor Microenvironment: It’s the RAGE Univ. of Michigan, Dept. of Immunology Ann Arbor, MI

(Author & Presenter) NIH student and post-doc seminar series Seminar Inflammation-induced immune suppression in cancer: It’s the RAGE NIH NIH, Bethesda, MD

(Author & Presenter) Midwinter Immunology conference Lecture Inflammation, Alarmins, and Immune Suppression – It’s the RAGE Midwinter Immunology conference Asilomar, CA

Uniformed Services University of the Health Sciences Lecture Inflammation-induced immune suppression in cancer: It’s the RAGE Uniformed Services University of the Health Sciences Bethesda, MD

(Author & Presenter) (Coordinator/Organizer) Progress in Vaccination Against Cancer (PIVAC) 15 Lecture The continuing saga of understanding & improving anti-tumor immunity: from cancer vaccines to myeloid-derived suppressor cells & PDL1 Progress in Vaccination Against Cancer Society Tubingen, Germany

4th International Symposium on Regulators of Adaptive Immunity Lecture Inflammation-induced immune suppression in cancer: It’s the RAGE Erlangen University U. of Erlangen, Germany

Institute for Human Virology Lecture Inflammation-induced immune suppression in cancer: It’s the RAGE Institute for Human Virology Baltimore, MD

International Congress of Immunology Lecture Tumor-induced Inflammation and Immune Suppression – It’s the RAGE International Congress of Immunology Milan, Italy

Japanese Society of Cancer Immunology Annual meeting Keynote/Plenary Address Inflammation-induced immune suppression in cancer: Myeloid-derived suppressor cells Japanese Society of Cancer Immunology Yamaguchi, Japan

The Association for Cancer Immunotherapy (CIMT) annual conference Lecture Inflammation, alarmins, and immune suppression - It's the RAGE CIMT Mainz, Germany

Cancer Immunotherapy and Immunomonitoring (CITIM) Keynote/Plenary Address Inflammation, alarmins, and immune suppression - It's all about RAGE CITIM Krakow, Poland

(Presenter) Progress in vaccination against cancer 12 (PIVAC12) Keynote/Plenary Address A tale of two cytokines: inflammation-amplified cross-talk between myeloid cells drives tumor progression. PIVAC Nottingham, UK