Research
Our lab studies how cells communicate with one another, a process that regulates nearly all aspects of animal development and, when damaged, leads to many diseases including cancer. Transmembrane proteins are the essential factors that transmit fate signals from the cell's external environment to its interior. In this regard, transmembrane proteins serve as gatekeepers whose initial decisions ultimately determine a cell fate pathway’s final activity state. Much previous research has focused on gene-regulatory events that control cell fate decisions. In contrast, we understand far less about how transmembrane proteins are regulated to produce proper amounts of downstream signals at the right times and places within the organism. This has limited our ability to control cell fate signaling therapeutically. The Myers lab is studying the biochemical and biophysical mechanisms that regulate transmembrane protein activity in cell fate pathways. A better understanding of these processes will help us to therapeutically manage birth defects, regenerative disorders, and malignancies.
Our lab studies how cells communicate with one another, a process that regulates nearly all aspects of animal development and, when damaged, leads to many diseases including cancer. Transmembrane proteins are the essential factors that transmit fate signals from the cell's external environment to its interior. In this regard, transmembrane proteins serve as gatekeepers whose initial decisions ultimately determine a cell fate pathway’s final activity state. Much previous research has focused on gene-regulatory events that control cell fate decisions. In contrast, we understand far less about how transmembrane proteins are regulated to produce proper amounts of downstream signals at the right times and places within the organism. This has limited our ability to control cell fate signaling therapeutically. The Myers lab is studying the biochemical and biophysical mechanisms that regulate transmembrane protein activity in cell fate pathways. A better understanding of these processes will help us to therapeutically manage birth defects, regenerative disorders, and malignancies.
Hedgehog Signal Transduction
Much of our work focuses on the Hedgehog (Hh) pathway, a quintessential cell fate specification cascade and a fascinating model for how membrane proteins and lipids influence cell fate decisions. Hh is a major player in development and regeneration, directing the patterning of nearly every vertebrate organ. Insufficient Hh signaling is linked to common birth defects, while pathway overactivation drives several common cancers. Yet surprisingly, the critical biochemical events regulating Hh signaling at the membrane remain largely unknown. We are dissecting the biochemical processes that enable cells to respond to Hh signals. Our approach utilizes novel optical, biochemical, and electrical sensors to monitor key Hh signal transduction events as they unfold in real-time. By using these sensors to study key Hh pathway steps in both living and cell-free systems, we are gaining a deeper understanding of the underlying transduction mechanism.
Much of our work focuses on the Hedgehog (Hh) pathway, a quintessential cell fate specification cascade and a fascinating model for how membrane proteins and lipids influence cell fate decisions. Hh is a major player in development and regeneration, directing the patterning of nearly every vertebrate organ. Insufficient Hh signaling is linked to common birth defects, while pathway overactivation drives several common cancers. Yet surprisingly, the critical biochemical events regulating Hh signaling at the membrane remain largely unknown. We are dissecting the biochemical processes that enable cells to respond to Hh signals. Our approach utilizes novel optical, biochemical, and electrical sensors to monitor key Hh signal transduction events as they unfold in real-time. By using these sensors to study key Hh pathway steps in both living and cell-free systems, we are gaining a deeper understanding of the underlying transduction mechanism.
The Primary Cilium
Apart from its roles in development and cancer, Hh is perhaps the best model for signal transduction within the vertebrate primary cilium. The cilium is a tiny microtubule-based membrane protrusion critical to the development and function in the nervous, cardiovascular, and musculoskeletal systems. Mutations in ciliary components affect numerous aspects of human physiology and can profoundly influence cancer progression. However, the mechanistic basis for such defects is generally not understood because ciliary signaling pathways are often studied with indirect methods that are unable to fully reveal the elaborately choreographed signaling events within this organelle. We are shedding light on this question by elucidating the underlying physiology of primary cilia – a fascinating area of biology that remains largely unexplored.
Apart from its roles in development and cancer, Hh is perhaps the best model for signal transduction within the vertebrate primary cilium. The cilium is a tiny microtubule-based membrane protrusion critical to the development and function in the nervous, cardiovascular, and musculoskeletal systems. Mutations in ciliary components affect numerous aspects of human physiology and can profoundly influence cancer progression. However, the mechanistic basis for such defects is generally not understood because ciliary signaling pathways are often studied with indirect methods that are unable to fully reveal the elaborately choreographed signaling events within this organelle. We are shedding light on this question by elucidating the underlying physiology of primary cilia – a fascinating area of biology that remains largely unexplored.
How Transmembrane Signaling Specifies Cellular Identity
Throughout animal biology, membrane proteins and lipids are indispensable in determining cellular identity and are often misregulated in cancer. Nevertheless, these molecules remain understudied due to a lack of appropriate tools. Our research on Hh and ciliary pathways will provide a blueprint to tackle other cell fate pathways whose membrane signaling mechanisms are poorly characterized. These studies will dramatically increase our understanding of an entire class of critical regulatory events that specify cell fate. They will also help us engineer better drugs to effectively control transmembrane protein activity while minimizing issues like drug resistance and side effects.
Throughout animal biology, membrane proteins and lipids are indispensable in determining cellular identity and are often misregulated in cancer. Nevertheless, these molecules remain understudied due to a lack of appropriate tools. Our research on Hh and ciliary pathways will provide a blueprint to tackle other cell fate pathways whose membrane signaling mechanisms are poorly characterized. These studies will dramatically increase our understanding of an entire class of critical regulatory events that specify cell fate. They will also help us engineer better drugs to effectively control transmembrane protein activity while minimizing issues like drug resistance and side effects.