"Support from The Sontag Foundation offers my laboratory the opportunity to use basic research on survival and adaptive plasticity within the central nervous system to gain insight into mechanisms underlying brain cancer and to aid in the identification of potential therapeutic targets."
- Dr. Mollie K. Meffert
- Associate Professor, Biological Chemistry, Johns Hopkins School of Medicine
About DSA-Funded Research
Cancer is thought to develop in phases. An initiating event, generally involving genetic damage, is followed by a promotion phase involving proliferation of initiated pre-cancerous cells and the possibility of incurring additional genetic mutations. The NF-kB proteins regulate transcription and are key players in tumor promotion in many tissues. NF-kB activation not only increases the expression of genes causing cells to grow and multiply, but also inhibits cell death by inducing death-suppressing genes. In healthy tissue, NF-kB contributes to cell survival and defense from toxic stimuli. However, uncontrolled NF-kB activation is found in tumors from many different tissues and can essentially "immortalize" cells as well as rendering them resistant to chemo- or radiotherapy. Components of the NF-kB signaling pathway are therefore attractive therapeutic targets for multiple cancers. Recently, uncontrolled NF-kB activation was documented in both glioblastoma and neuroblastoma tumors, indicating that it may feature prominently in tumor biology of the central nervous system (CNS) as well. However, NF-kB's role in apoptosis and proliferation within the CNS is far less clear than in other tissues since both pro-death and pro-survival functions have been reported. This proposal aims to shed light on the puzzle of how NF-kB regulates survival and proliferation in the brain by investigating the possibility that different outcomes could result from NF-kB activation in distinct cell types and pathways. Ultimately, our goal is to gain insights that provide direction for achieving specificity in therapeutic efforts to target NF-kB in CNS tumors while minimizing adverse effects on healthy tissue.
"Mollie is both an effective and dedicated bench scientist and a thoughtful analyst of the meaning of her results. She is fully prepared to make discoveries that will materially move neuroscience ahead."
David Baltimore, Ph.D.
California Institute of Technology, Pasadena
"I would describe Mollie as being the most open minded and the most willing and able to chart a new scientific direction with a great deal of independence... . She will aggressively and successfully pursue important cancer research."
Howard Schulman, Ph.D.