Massey researcher awarded $1.5M to study enzyme's role and relationship to the growth of melanoma and colorectal cancer
VCU Massey Cancer Center researcher Rong Huang, Ph.D., was recently awarded a $1.5 million grant from the National Institute of General Medical Sciences to study the structure, regulation and inhibition of a class of proteins that have been previously implicated to be involved in the development of malignant melanoma and colorectal cancer. She hopes the results of the five-year study will eventually lead to her long-term goal of discovery of new, effective cancer therapies.
The R01 grant will fund a research project titled “Protein N-Terminal Methylation Mechanisms and Inhibition,” in which Huang will lead a team of investigators studying a new class of enzymes called protein N-terminal methyltransferases (NTMTs) that catalyze protein alpha-N-terminal methylation. This methylation plays an essential role in regulating cell mitosis, chromatin interactions and DNA repair. The research team hopes to fully understand the biochemical pathways through which these enzymes contribute to cancer growth and potentially create effective drugs that inhibit their effects.
An overexpression of NTMTs were found in more than 90 percent of the tissue in malignant melanoma cancer patients, compared to a relatively low expression in normal tissues. Although it is a rare form of skin cancer, melanoma is the most severe, claiming responsibility for nearly three-quarters of all skin cancer deaths. Melanoma rates have been on the rise for the past three decades, and the American Cancer Society estimates that more than 76,000 new melanomas will be diagnosed in 2016.
A similarly high expression level of NTMTs was also detected in other cancers including colorectal cancer, which is the third most common cancer diagnosed among both men and women in the United States.
This overexpression lead Huang to believe that NTMTs might act as significant contributors to the pathogenesis (biological progression) of cancer and other developmental defects.
Although the research is primarily focused on elucidating the biochemical pathways mediated by NTMTs that contribute to the pathogenesis of cancer, Huang hopes the findings will provide tools for scientists to investigate the impacts of this methyltransferase family and functions of other similar protein methyltransferases.
“We believe that this research effort has the great potential to provide a clearer understanding of mechanisms and inhibition of NTMTs, and shed light on the biological impact of protein N-terminal methylation,” said Huang, a member of Massey’s Developmental Therapeutics research program, an assistant professor in medicinal chemistry and member of the Institute for Structural Biology, Drug Discovery and Development at the VCU School of Pharmacy.
Huang also said that a long-term goal is to use her research findings to develop new drugs that treat cancer through the inhibition of NTMTs.
“Blocking damaged DNA repair pathways and cell division represents a new approach to personalized cancer therapy since it may sensitize cancer cells to the DNA-damaging effects of chemotherapy,” Huang said. “Accomplishment of the proposed work will not only provide new chemical tools for both basic NTMT biology research, but also facilitate the development of novel therapeutic approaches to target NTMT and NTMT-involved pathways.”
Huang earned her Ph.D. in medicinal chemistry at Purdue University, and completed a postdoctoral fellowship in chemical biology at Johns Hopkins University. She joined Massey in 2011.
She is collaborating on this research with Jinrong Min, Ph.D., of the Structural Genomics Consortium at the University of Toronto; and Darrell L. Peterson, Ph.D., professor in biochemistry and molecular biology at the VCU School of Medicine.