Cancer cachexia is the simultaneous wasting away syndrome of fat and muscle tissue. It is prevalent in 50% of all cancer patients, and it’s ultimately responsible for 25% of all cancer deaths. A 5% or greater weight loss is the clinical definition of this syndrome, but a molecular definition is needed to enable an unbiased exploration of this process. We’ve developed both in vivo xenographs of human cancer cell lines in nude mice and in vitro models of primary human target tissues of cachexia (e.g. skeletal muscle and adipose) upon which we will examine the effects of cachexia-inducing and non-inducing cancer cell lines. We have shown that these models recapitulate relevant pathophysiologic responses on a biochemical, morphological, and transcriptional level and will allow us to generate a robust molecular definition of this complex disease. These high-throughput models will also enable us to interrogate cachexia's underlying biology in an unbiased manner using genomic approaches such as metabolomic and proteomic analysis of the secreted factors that drive this process and the genetic programs that initiate it through genome-wide loss-of-function and gain-of-function experiments.
PROJECT: Genomic Approaches to Cancer Cachexia: Models and Assays
The SRPG program has been an invaluable summer experience which has really opened my eyes to a new generation of science. I’ve been fortunate enough to engage in discussions and even work with some of the innovative scientists at the Broad. From all my interactions with these individuals, perhaps the most valuable lesson that I’ve learned is not to be afraid of tackling complex problems. Scientists at the Broad are passionate about what they do, but what makes this institution so special is its collaborative spirit. It’s contagious. Everyone is so excited about these ambitious projects and wants to be a part of them. This community-wide drive across many different disciplines really raises the bar and ultimately leads to significant progress in science and technology.