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Suzanne Ostrand-Rosenberg

Prof. Biology, Robert+Jane Meyerhoff Chair

Biological Sciences
Biological Sciences Bldg, Room 221
Phone
410-455-2237
srosenbe@umbc.edu
Education
Ph D, California Institute of Technology (1975)
Other, Barnard College, Columbia University (1970)
CV View CV
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 (Supporting) Mechanisms of trans-cell action of tumor suppressors expressed in myeloid cells Grant (Currently Under Review) Sponsored by NIH (Sep 1, 2018)

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 – Jun 30, 2018)

Ostrand-Rosenberg, Suzanne

Ostrand-Rosenberg, Suzanne (Supporting) Eduardo, Davila (Principal) Amplifying TCR Responses and Resisting MDSC-mediated Suppression via MyD88 Signaling in T cells Grant (Not Funded) Sponsored by NIH

Intellectual Contributions

vol. 51 68-75 Current Opinion in Immunology .

vol. 17 486-498 American Society of Biological Chemistry Journal of Proteome Research .

vol. 200 422-431 American Association of Immunologists Journal of Immunology .

vol. 17 315-324 American Society of Biological Chemistry Journal of Proteome Research .

vol. 6 59-68 American Association of Cancer Research Cancer Immunology Research .

CD3xPDL1 bi-specific T cell engager (BiTE) simultaneously activates T cells and kills PDL1+ tumor cells vol. 8 57964-57980 Oncotarget

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

Tumor Immunoenvironment NY, Heidelberg,Dordrecht, London Springer

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

Understanding the Tumor Immune Microenvironment (TIME) for effective therapy springer/Nature Nature Medicine

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

Research in Progress

Myeloid-derived suppressor cells (MDSC) promote tumor progression and weight gain, but protect against metabolic dysfunction in obese mice Scholarly (On-Going) Mar 1, 2015

Presentations

1st European Symposium on Myeloid Regulatory Cells in Health and Disease Lecture Mye-EUNITER Essen, Germany

Infection and Immunity Research Forum (IIRF) Annual conference Keynote/Plenary Address IIRF Western University, London, Ontario Canada

Progress in Vaccination Against Cancer 18 Lecture PIVAC 18 Oslo, Norway

Frontiers in Molecular Oncology International Conference Keynote/Plenary Address Myeloid-derived suppressor cells: Potent immune suppressors in the tumor microenvironment Universidade Estadual Paulista Sao Paulo, Brazil

(Author & Presenter) American Association of Immunologists Annual conference Lecture Writing Scientific Manuscripts and Responding to Reviewers American Association of Immunologists Austin, TX

(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