Ofer Reizes, PhD
Staff
The Laura J. Fogarty Endowed Chair for Uterine Cancer Research
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
There is a dearth of targeted therapies for women’s cancers and our projects seek to address this shortage by a focused approach on novel new pathways that we recently discovered. We focus on the most therapeutically challenging triple negative breast and gynecologic cancers. Due to limited available therapies, less than 50% of women survive more than 5 years with these cancers.
Biography
Ofer Reizes, PhD is professor and staff in the Department of Cardiovascular and Metabolic Sciences at the Cleveland Clinic Lerner Research Institute (LRI) and the inaugural holder of The Laura J. Fogarty Endowed Chair for Uterine Cancer Research. Dr. Reizes earned a Bachelor of Arts in Molecular and Cellular Biology from the University of Maryland – Baltimore County and a PhD in molecular pharmacology from the University of Texas Southwestern Medical Center – Dallas. He subsequently pursued a post-doctoral fellowship in developmental biology and metabolic disease from The Children’s Hospital Boston/Harvard Medical Center. In 2001, Dr. Reizes was recruited to Procter & Gamble Pharmaceuticals where he led drug discovery efforts in metabolic diseases for 5 years. In 2006, he moved from industry to academia to investigate the mechanistic links between metabolic disease and cancer.
His lab at the Cleveland Clinic focuses on unmasking chemoresistance mechanisms in breast and gynecologic cancers to identify strategies to improve patient outcomes. The research includes investigation of cancer stem cells, hyperthermic intraperitoneal chemotherapy and the impact of the microbiome on tumor growth and chemosensitivity. Dr. Reizes applies his previous drug discovery and development expertise to identification and approaches for cancer therapeutics. His research is published in multiple high impact journals including Cell, Journal of Clinical Investigation, Journal of Experimental Medicine, Nature Communications, Cancer Research and Molecular Cancer.
Education & Professional Highlights
Post-doctoral Fellowship, Developmental Biology and Endocrinology
The Children’s Hospital Boston – Harvard Medical School
1999
PhD, Molecular Pharmacology
University of Texas – Southwestern Medical Center at Dallas
1993
BA, Molecular and Cellular Biology
University of Maryland – Baltimore County
1987
Professional appointments
Cleveland Clinic Lerner Research Institute
Staff
present
The Laura J. Fogarty Endowed Chair for Uterine Cancer Research
Holder
Present
Cleveland Clinic Lerner Research Institute
Associate Staff
2006 - 2014
Procter & Gamble Pharmaceutical, Metabolic Diseases Discovery
Senior Scientist
2001 - 2006
The Children’s Hospital Boston -- Harvard Medical School
Research Instructor
1999 - 2001
Research
Complement independent signaling in ovarian cancer.
In the U.S., ovarian cancer is the second most common gynecologic malignancy, but the top cause of gynecologic cancer death, and is responsible for 5% of all cancer deaths in women. In 2017, 22,440 new cases and 14,080 deaths are estimated to occur. Of these, 10% of ovarian cancers demonstrate an appearance of endometrioid tumor (ET) subtype.
Treatment for gynecologic malignancy is traditionally comprised of debulking surgery and platinum/taxane-based chemotherapy. Patients initially respond to cytotoxic chemotherapy, however for many the tumor recurs and becomes resistant to platinum. As such, there is a significant unmet medical need to treat ETs. An underlying cause of this resistance is the presence of a cancer stem cell population that contributes to tumor growth, recurrence, and treatment resistance and has been observed in ETs. CSCs offer a potential target population for therapeutic intervention. In published studies, we identified the cell surface protein CD55 as a therapeutic target for ET cancer stem cells and platinum-resistant disease. Our studies focus on defining mechanisms for overcoming resistance and targeting cancer stem cells.
Connexin/Focal Adhesion Kinase/NANOG complex in Triple Negative Breast Cancer.
Triple-negative breast cancer is the most aggressive breast cancer subtype and is resistant to therapies. Our objective is to identify unique, targetable mechanisms to neutralize cancer stem cells, which are thought to underlie resistance to chemotherapeutics, as well as recurrence and metastasis, and minimize collateral damage to surrounding cells. To identify key processes that are important for cancer stem cell function, we developed a reporter system to track and study these cells in real time. With this reporter, we identified that the protein connexin 26 (Cx26) is necessary and sufficient for the survival of cancer stem cells in triple-negative breast cancer models. While Cx26 was previously proposed to be a tumor suppressor, epidemiological studies suggest otherwise, as patients with high Cx26 had a poorer prognosis. Our studies indicate that Cx26 promotes cancer stem cell survival by forming a protein complex with the transcription factor NANOG, a master regulator of cancer stem cell function, and focal adhesion kinase in triple-negative breast cancer but not in other breast cancers. Our objective is to prevent this complex from forming and thereby inhibit cancer stem cell survival and growth.
Our Team
Selected Publications
Reizes, O., Lincecum, J., Wang, Z., et al. Transgenic expression of syndecan-1 uncovers a novel control of feeding behavior by hypothalamic syndecan-3. Cell 2001, 106: 105-116
Strader, A.D*, Reizes, O.* et al. Syndecan-3 null mice are resistant to diet induced obesity. J. Clin. Invest. 2004, 114: 1354-1360.
Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale JS, Rao V, Demelash A, Saygin C, China A, Alban TJ2, Hitomi M, Torre-Healy LA, Alvarado AG, Jarrar A, Wiechert A, Adorno-Cruz V, Fox PL, Calhoun BC, Guan JL, Liu H, Reizes O, Lathia JD. Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase. Nat Commun. 2018 Feb 8;9(1):578. doi: 10.1038/s41467-018-02938-1.
Saygin C, Wiechert A, Rao VS, Alluri R, Connor E, Thiagarajan PS, Hale JS, Li Y, Chumakova A, Jarrar A, Parker Y, Lindner DJ, Nagaraj AB, Kim JJ, DiFeo A, Abdul-Karim FW, Michener C, Rose PG, DeBernardo R, Mahdi H, McCrae KR, Lin F, Lathia JD, Reizes O. CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors. J Exp Med. 2017 Sep 4;214(9):2715-2732. doi: 10.1084/jem.20170438. Epub 2017 Aug 24.
Careers
Research News
Two investigators are combining their expertise to better understand protein CD55 and its role in chemoresistance.
Discovering a new way a protein behaves in ovarian cancer led to new research, potential treatments.
A peptide drug candidate based on a Cleveland Clinic discovery disrupted cancer growth and self-renewal.
Reassessing antibiotic dosage and type could improve survival rates in deadliest gynecologic malignancy, Cleveland Clinic research finds.
Triple-negative breast cancer (TNBC) cells lack the receptors needed to bind to hormones and growth factors, meaning typical cancer treatments that target these areas are ineffective.