Rosalind Segal, MD, PhD

Sensory Neurons

The nervous system inputs sensory information, processes that information, and executes actions, so we can interact with the world around us. Several specialized attributes of sensory neurons enable input of information about our surroundings: these neurons have distinctive nerve endings that are in close contact with the external environment, their axons traverse great distances and they are able to transmit information rapidly and unidirectionally. Much of our research focuses on the largest set of primary sensory neurons, the dorsal root ganglia (DRG) neurons that innervate the skin and transmit sensations of touch, pain, temperature and motion.

• How is gene expression regulated in distinct intracellular sites within large sensory neurons?

Sensory neurons traverse long distances. However it is not known how proteins are differentially localized within distinct intracellular domains of sensory neurons, so that peripheral axons can initiate tactile sensation and central axons can form synapses in the spinal cord. Recent studies have highlighted the importance of mRNA transport and localized protein synthesis in spatial regulation of gene expression. We have identified mRNAs that are localized and translated in the peripheral axons of sensory neurons. We are addressing how RNA binding proteins orchestrate mRNA trafficking and protein expression within peripheral terminals and so enable tactile sensation.

• How do long peripheral axons withstand damage so they are maintained throughout life?

We identified the bcl2 family member bclw as an anti-apoptotic component highly expressed in axons of sensory neurons, and we demonstrated that loss of bclw results in progressive, sensory neuropathy due to axonal degeneration.  Current studies to define mechanisms that regulate bclw expression, and to determine how bclw exerts its distinctive ability to promote axon viability and prevent axon degeneration may lead to new therapeutic approaches for degenerative disorders that impact sensory neurons.

Brain Tumor Biology

A major project in the laboratory focuses on brain tumor biology.  Brain tumors now represent the most common cause of cancer-related death in children.  New genomic insights identify several key pathways that promote regulated growth during development, and also contribute to deregulated growth of pediatric brain tumors, including the Sonic Hedgehog (Shh) pathway. Our studies focus on the biology of the Shh signaling pathway in development and disease. Current studies are aimed at developing therapeutic approaches to pediatric brain tumors by targeting novel components in the Shh signaling cascade or by targeting synergistic signaling pathways.

"Several specialized attributes of sensory neurons enable input of information about our surroundings."