Cancer, we now know, is caused by the uncontrolled growth of a single cell. . . In a normal cell, powerful genetic circuits regulate cell division and cell death. In a cancer cell, these circuits have been broken, unleashing a cell that cannot stop growing.
That this seemingly simple mechanism – cell growth without barriers – can lie at the heart of this grotesque and multifaceted illness is a testament to the power of cell growth.
            -Siddhartha Mukherjee, The Emperor of All Maladies


Cell signaling and metabolism in cancer, metabolic diseases, and aging.

Research in the Manning Lab is focused on unraveling the key regulatory circuits that control cell growth. They are delineating how signals from nutrients and growth factors are propagated to coordinately regulate metabolism, with implications in a wide variety of complex human diseases. Research efforts are defining the molecular control mechanisms and functions of the ubiquitous PI3K-mTOR signaling network, which senses and relays signals from nutrients and other growth cues to alter key metabolic processes in cells and tissues.

The PI3K-mTOR network integrates diverse signals and underlies a wide array of pathological states

Frequent dysregulation of the PI3K-mTOR network contributes to a diverse set of seemingly unrelated human diseases, including those with uncontrolled cell growth and metabolism as an underlying feature. This network is aberrantly regulated in, or believed to contribute to, the majority of human cancers, genetic tumor syndromes (e.g, tuberous sclerosis complex, lymphangioleiomyomatosis, PTEN syndrome), metabolic diseases (e.g., obesity, diabetes, cardiovascular disease), autoimmune and inflammatory diseases (e.g., arthritis, lupus, hepatitis), and neurological disorders (e.g., epilepsy, autism, neurodegeneration). This signaling network also influences the lifespan of organisms and serves as a major connection between diet and the aging process. The Manning lab seeks to decipher the circuitry of the PI3K-mTOR network under both physiological and pathological states, and how its downstream functions contribute to metabolic homeostasis and dysfunction in human health and disease.


Areas of Focus for the Manning Lab