Brian Rubin, MD, PhD
Staff
Location: Cleveland Clinic Main Campus
Research
Our laboratory is focused on understanding the pathogenesis of bone and soft tissue cancers, collectively known as sarcomas. We take a comprehensive approach by analyzing actual human tumors, human tumor cell lines, mouse tumor cell lines and mouse models. Our major focus is to understand signal transduction pathways in sarcomas to identify therapeutic targets. Our major project is to understand the pathogenesis of gastrointestinal stromal tumor (GIST), the most common sarcoma of the gastrointestinal tract. Most GISTs harbor activating mutations in either KIT or PDGFRA, which encode receptor tyrosine kinases important in cellular proliferation. By targeting KIT and PDGFRA with small molecule inhibitors such as imatinib mesylate (Gleevec, Novartis) or sunitinib maleate (Sutent; Pfizer), we can “turn off” KIT and PDGFRA signaling, which has a dramatic effect on patients with GIST. However, drug resistance is an increasing problem. We have developed cell lines and genetically engineered mouse models to address these issues and have begun to probe the mechanisms of drug resistance. We are also using these models to study various aspects of disease progression. Finally, we use our mouse models as preclinical systems to test new therapies.
Biography
Brian Rubin, MD, PhD, is certified by the American Board of Pathology in anatomic pathology. He specializes in the diagnosis of diseases of bone and soft tissue and is an expert in the diagnosis of sarcomas.
Education & Professional Highlights
Education & Fellowships
Residency - Brigham & Women's Hospital
Anatomic and Clinical Pathology
Boston, MA USA
2000
Medical Education - Cornell University Medical College
MD
New York, NY USA
1995
Undergraduate - University of California at Berkeley
Berkeley, CA USA
1983
Professional Highlights
- Treasurer, International Society of Bone and Soft Tissue Pathology
- Board Member, Connective Tissue Oncology Society
- Member of Working Group, 2002 WHO Classification of Tumours of Bone and Soft Tissue
- Senior Associate Editor, Laboratory Investigation
Certifications
- Pathology - Anatomic Pathology
- Pathology - Pathology Recertification
Memberships
- International Society of Bone and Soft Tissue Pathology
- College of American Pathologists
- Connective Tissue Oncology Society
- United States and Canadian Academy of Pathology
- American Association for the Advancement of Science
Research
Our laboratory is focused on understanding the pathogenesis of bone and soft tissue cancers, collectively known as sarcomas. We take a comprehensive approach by analyzing actual human tumors, human tumor cell lines, mouse tumor cell lines and mouse models. Our major focus is to understand signal transduction pathways in sarcomas to identify therapeutic targets. Our major project is to understand the pathogenesis of gastrointestinal stromal tumor (GIST), the most common sarcoma of the gastrointestinal tract. Most GISTs harbor activating mutations in either KIT or PDGFRA, which encode receptor tyrosine kinases important in cellular proliferation. By targeting KIT and PDGFRA with small molecule inhibitors such as imatinib mesylate (Gleevec, Novartis) or sunitinib maleate (Sutent; Pfizer), we can “turn off” KIT and PDGFRA signaling, which has a dramatic effect on patients with GIST. However, drug resistance is an increasing problem. We have developed cell lines and genetically engineered mouse models to address these issues and have begun to probe the mechanisms of drug resistance. We are also using these models to study various aspects of disease progression. Finally, we use our mouse models as preclinical systems to test new therapies.
Our Team
Selected Publications
View publications for Brian Rubin, MD, PhD
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Rubin, BP et al. 2001. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 15:8118-8121.
Rubin, BP et al. 2002. Molecular targeting of PDGFB by imatinib mesylate (STI571/Gleevec) in a patient with metastatic dermatofibrosarcoma protuberans. J Clin Oncol 20:3586-3591.
Rubin BP et al. 2005. A knock-in mouse model of gastrointestinal stromal tumor harboring Kit K641E. Cancer Res 65:6631-6639.
Gupta A et al. 2010. Autophagy inhibition and antimalarials promote cell death in gastrointestinal stromal tumor (GIST). Proc Natl Acad Sci U S A 107:14333-14338.
Rubin BP et al. 2011. Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma. Cancer Cell 19:177-91.
Liang R et al.. 2011. The phosphatidyl inositol 3-kinase pathway is central to the pathogenesis of Kit-activated melanoma. Pigment Cell Melanoma Res 24:714-23.
Tanas MR et al. 2011. Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med. Aug 31;3(98):98ra82.
Careers
Research News
Dr. Rubin used a novel approach to target the gene fusion that causes epithelioid hemgioendothelioma, engineering a novel, first-of-its-kind mouse model of the disease, which will help advance studies to identify new treatments.