Brian P. Rubin, M.D., Ph.D.

Staff

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:L2-237
rubinb2@ccf.org
Phone: (216) 445-5551
Fax: (216) 445-3707



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.


Ashley  Burtscher B.S.
Ashley Burtscher B.S.
Research Technologist

Location:NE2-215
Phone:(216) 445-4841
kendiga@ccf.org
Fax:(216) 444-0512
laboratory

Kepeng  Che Ph.D.
Kepeng Che Ph.D.
Postdoctoral Fellow

Location:NE2-216B
Phone:(216) 445-4841
chek@ccf.org
Fax:(216) 444-5012
laboratory

Shuang  Ma Ph.D.
Shuang Ma Ph.D.
Research Associate

Location:NE2-216B
Phone:(216) 445-4841
mas@ccf.org
Fax:(216) 444-0512
laboratory

Andrea  Wallace B.S.
Andrea Wallace B.S.
Research Technologist

Location:NE2-216B
Phone:(216) 445-4841
wallaca2@ccf.org
Fax:(216) 444-0512
laboratory


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.