Boston University School of Medicine (BUSM) researchers Neil Joseph Ganem, PhD and Anurag Singh, PhD, each have received the Jackie King Young Investigator Awards from the Melanoma Research Alliance (MRA), the largest private funder of melanoma research. Both serve as assistant professors of pharmacology & experimental therapeutics and medicine.
Ganem's research focuses on uncovering the cellular defects that generate chromosome instability in human cancer cells. Preliminary data suggests that oncogenic BRAF (a gene that makes a protein called B-Raf and is involved in cell growth), which is one of the most common drivers of melanoma, may be a potent driver of chromosome instability in melanoma. "Normally, BRAF plays an important role in promoting cell proliferation and is turned on and off appropriately. However, our data suggest that oncogenic BRAF may also contribute to tumor development in a totally new way: by driving chromosome instability. Currently, my lab is attempting to define the mechanisms through which oncogenic BRAF promotes abnormal chromosome segregation and instability, explained Ganem.
In addition, his lab has recently developed an innovative screening approach to comprehensively identify the proteins and molecular pathways required for chromosomally unstable cancer cells to survive and proliferate. "Ultimately, our long-term scientific goal is to develop new strategies to specifically inhibit the growth of abnormal, chromosomally unstable cancer cells expressing oncogenic BRAF while sparing the normal cells from which they originated," Ganem added.
Singh's research involves the functional characterization of gene mutations that drive cutaneous melanoma progression. A number of gene mutations promote the transformation of normal skin melanocyte cells into aggressive cancerous cells. An example is the gene known as NRAS, which is mutated in 20 percent of melanoma cases. "The NRAS oncogene promotes the survival of cancerous melanoma cells. However, it is difficult to block the function of mutant NRAS with anti-cancer agents since NRAS is considered undruggable," Singh explained. His lab studies how NRAS interacts and cooperates with other genes in cancerous melanoma cells to form gene networks, analogous to computer circuits. "We have identified two major types of NRAS networks in melanoma. We hypothesize that these "subtypes" can be treated with selective "targeted" anti-cancer agents or precision medicines. By identifying the key differences in the two types of NRAS networks, we hope to pinpoint vulnerabilities that can be blocked with pharmacological agents," said Singh.
"We are thrilled to be funding both of these researchers at Boston University School of Medicine. The caliber of grant applications was incredibly high, and the Grants Review Committee had the difficult task of selecting the premier research proposals worthy of funding," said Louise M. Perkins, PhD, Chief Science Officer at the Melanoma Research Alliance. "Our goal with this latest round of funding is to improve our understanding of existing melanoma therapies to bring hope to more patients."
Specific epigenetic pathway found to be involved in the development of melanoma drug resistance