2012 Research Grants
Identification and characterization of novel ribosome-associated proteins and their role in the development of blood cancers.
Conducted by Dr. Anne Bothmer at the Beth Israel Deaconness Medical Center, Harvard Medical School. Funded in Partnership with the Damon Runyon Cancer Research Foundation.
Dr. Anne Bothmer will peer into the “black box” of cellular machinery to determine how protein production in cancerous cells differs from that in healthy cells, and how those differences may lead to diseases such as acute myeloid leukemia (AML.) She is investigating a major pathway that affects more than a third of AML patients: the development of cancer from a mutation in the gene NPM1 and the resulting abnormal functioning of a crucial regulator called NPM.
Dr. Bothmer’s theory is that when NPM's functioning is impaired, cellular complexes called "ribosomes" that coordinate the fabrication of proteins are altered and as a result, prevented from playing their intended role in the production of blood cells. As shown in the diagram below, the questions of how ribosomes are altered and the role they play in blood cancers remains a mystery. With the results of Dr. Bothmer’s research, we should be better able to understand the mechanism that leads from gene mutation to disease, and reveal novel targets for therapy that would not otherwise be evident.
Dr. Bothmer, here presenting a poster of her research, will be working with Dr. Pier Paolo Pandolfi at Beth Israel Deconness Medical Center, using a novel mass spectrometry method to analyze differences between normal and cancerous cells. She will also be working in collaboration with Dr. Robert Darnell at Rockerfeller Unversity using techniques of high-throughput sequencing of RNA to understand how the absence of NPM alters the landscape around cellular machinery and can lead to AML and other blood cancers.