TOBEY J MACDONALD, MD
Medical Practice at Michigan Ave, Washington, DC
License number
DC MD31175
Category
Medical Practice
Type
Pediatric Hematology-Oncology
Address
Address
111 Michigan Ave NW, Washington, DC 20010
Phone
(202) 884-2140
Personal information
See more information about TOBEY J MACDONALD at radaris.comName
Address
Phone
3000 Connecticut Ave NW, Washington, DC 20008
Professional information
Tobey J Macdonald, Washington DC
Specialties:
Pediatric Hematologist / Oncologist
Address:
111 Michigan Ave Nw, Washington, DC 20010
Education:
Cornell University, Weill Cornell Medical College - Doctor of Medicine
Childrens Hospital Los Angeles - Fellowship - Pediatric Hematology/Oncology (Pediatrics)
Childrens Hospital Los Angeles - Fellowship - Pediatric Hematology/Oncology (Pediatrics)
Board certifications:
American Board of Pediatrics Certification in Pediatrics, American Board of Pediatrics Sub-certificate in Pediatric Hematology/Oncology (Pediatrics)
Gene Expression Based Method For Distinguishing Metastatic From Non-Metastatic Forms Of A Tumor, And Use In Designing Therapeutic Drugs
US Patent:
2004012, Jul 1, 2004
Filed:
Aug 29, 2001
Appl. No.:
09/940454
Inventors:
Dietrich Stephan - Falls Church VA, US
Tobey MacDonald - Washington DC, US
Kevin Brown - Washington DC, US
Tobey MacDonald - Washington DC, US
Kevin Brown - Washington DC, US
International Classification:
C12Q001/68
US Classification:
435/006000
Abstract:
Gene expression profiling of tumors, clinically designated as either metastatic (M+) or non-metastatic (M0), identifies genes whose expression differed significantly between classes. A class-prediction algorithm based on these medulloblastoma genes assigned the sample class to these tumors (M+ or M0) with 72% accuracy and to four additional independent tumors with a 100% accuracy. Class prediction also assigned the metastatic medulloblastoma cell line Daoy to the metastatic class. Notably upregulated in the M+ tumors were platelet derived growth factor receptor alpha (PDGFRA) and members of the downstream RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway. Immunohistochemical validation on an independent set of tumors showed significant overexpression of PDGFRA in M+ tumors as compared to M0 tumors. In in vitro assays, PDGFA enhanced medulloblastoma migration and increased downstream MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK1 (p42 MAPK), and MAPK3 (p44 MAPK) phosphorylation in a dose-dependent manner. Neutralizing antibodies to PDGFRA or U0126, a highly specific chemical inhibitor of MAP2K1 and MAP2K2 known as U0126, blocked MAP2K1, MAP2K2, and MAPK1/3 phosphorylation, inhibited migration, and prevented PDGFA-stimulated migration. These results provide the first insight into the genetic regulation of medulloblastoma metastasis and are the first to suggest a role for and the RAS/MAPK signaling pathway in medulloblastoma metastasis. Inhibitors of PDGFRA and RAS proteins, among others overexpressed M+ genes identified herein, represent novel therapeutic targets in medulloblastomas and other M+/MO tumors. The inventive method of prediction and targeted therapy is applicable to any tumor that exists in both M+ and MO forms, such as the neurotumors glioma, neuroblastoma and ependymoma, as well as lung and breast cancers.