Igor V. Garkavtsev, MD, PhD
Assistant Professor of Radiation Oncology
Harvard Medical School
Edwin L. Steele Laboratory for Tumor Biology
As part of the Edwin L. Steele Laboratory for Tumor Biology, research at the Garkavtsev Lab focuses on mechanisms governing the development of brain tumors, with primary emphasis on the identification and characterization of novel tumor suppressor genes. We are particularly interested in understanding how these genes are involved in the regulation of brain tumor angiogenesis and invasion. A detailed understanding of this regulation may lead to the rational selection of molecular targets for anti-cancer drug development.
Gliomas are the most common primary tumors of the central nervous system, with nearly 15,000 diagnosed annually in the U.S. and a mortality approaching 80% within the first year after diagnosis. Malignant gliomas are very aggressive, highly invasive, and one of the deadliest of human cancers.
Glioblastomas have been linked to the inactivation of the ING4 tumor suppressor gene. The predicted amino acid sequence revealed that ING4 encodes a protein containing 249 amino acids with a molecular mass of 29 kDa. ING4 expression is significantly diminished in gliomas compared to normal human brain tissue, and the extent of reduction correlates with tumor progression from lower to higher grades of tumors. We have shown that ING4 is a component of the NF-kB signaling pathway and that ING4 regulates brain tumor angiogenesis through transcriptional repression of the NF-kB target genes. The molecular mechanisms underlying upstream regulation and interaction of this gene with other brain tumor suppressors are under investigation.