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Amir Mitchell, PhD, assistant professor of molecular medicine in the Program in Systems Biology, has received the Maximizing Investigators' Research Award from the National Institute of General Medical Sciences to support research into cellular decoding of signaling dynamics.
Dr. Mitchell will use the five-year, nearly $2.1 million grant to study how intracellular dysfunctions, as mutations, corrupt information encoding and which cellular processes need to be targeted in order to restore proper encoding.
“Healthy cells in the human body use temporal patterns of activity in signaling pathways to encode information about the extracellular environment. Many diseases, foremost cancer, stem from corruption of these temporal signaling patterns which culminates in maladaptive outcomes as uncontrolled cell proliferation,” Mitchell said.
The Mitchell lab will focus on trying to understand the genetic and non-genetic mechanisms that contribute to different cellular “behaviors,” as signaling and gene expression.
“We want to take well studied cell lines and closely look at how two sister cells might respond differently to anti-cancer therapy. It’s quite remarkable and scary that differences in drug sensitivity can already manifest after a single cell division. The molecular mechanisms driving such differences can’t be based on de-novo genetic mutations. In the future, if we can target the mechanism that allows cells to rapidly diverge in behavior, we will perhaps be able to target these mechanisms and compel cells to force behave more homogeneously. Homogeneous cell response can greatly simplify treatment,” he said.
To conduct the research, the Mitchell lab will use high-throughput microscopy and screening approaches to identify and segregate the cells that behaved differently.
“This research will impact the broad scientific community by demonstrating a strategy and methodology for resolving the intricate connections between signaling dynamics and cell-fate decisions – a connection that emerges as fundamental for many cell decisions and multiple diseases,” Mitchell said.
