"The Venneti lab studies the relationship between cancer metabolism and epigenetics in brain tumors. Metabolic reprogramming is a hallmark of cancer that is essential to generate energy and biomass in tumor cells. Metabolic pathways can also directly regulate epigenetic pathways including DNA and histone methylation. We aim to define the interface between cancer metabolism and epigenetics in childhood ependymomas. Our work will help understand the pathology of these devastating tumors to enable the development of effective therapeutic strategies to treat these tumors."
- Dr. Sriram Venneti
- Assistant Professor, Department of Pathology and Neuropathology, University of Michigan Medical School, 2014-present
About DSA-Funded Research
Ependymomas in children occur mainly in the posterior fossa (EPF) of the brain and are devastating tumors. Current treatments including surgery and chemo/radiation therapy are not curative underscoring the importance to develop effective treatments. We have discovered that a subset of childhood EPF tumors with poor prognosis (designated group-A, EPF-A) exhibit increases in an epigenetic mark on a histone protein termed H3. DNA is wound around histones including histone H3. Histone H3 has an amino acid termed lysine (K) at position 27 designated as H3K27. H3K27 can undergo a process called acetylation, which enables increased gene expression. EPF-A tumors exhibited high acetylation of H3K27 levels and this corresponded to elevated expression of many genes related to glucose metabolism. Glucose is a central fuel for cancer cells and glucose metabolism enables the uncontrolled growth of tumor cells. We aim to prevent both H3K27 acetylation and the ability of ependymoma tumor cells to metabolize glucose. We expect that this will cause tumor cells to die and will lay the foundation to find effective treatments for children with ependymomas.
"Sriram is an outstanding academic pathologist and scientist with a clear vision for the future of neuro-oncology. His work on understanding metabolism and epigenetics in ependymomas and applying that knowledge to develop biomarkers will make him a leader in the field."
Charles A. Parkos, M.D., Ph.D.
University of Michigan
"Sriram is a superb clinical neuropathologist and a molecularly driven basic scientist who has the potential to influence the treatment -diagnosis-prevention of brain tumors using his innovative research methods."
Craig B. Thompson, M.D.
Memorial Sloan Kettering Cancer Center