Neurobiology

Qiufu Ma, Ph.D.

Associate Professor of Neurobiology

We are interested in investigating the mechanisms underlying the formation of the pain circuitry. In mammals, painful/noxious sensory information is detected by a specialized group of sensory neurons called nociceptors. These neurons express a diverse array of ion channels and receptors that respond to noxious thermal, chemical and mechanical stimuli. Noxious sensory information is relayed through the dorsal horn of the spinal cord to the brain. A major goal of our research is to understand how distinct classes of nociceptors and spinal relay neurons are specified during development.

To address these questions, we have taken a systematic approach to identify transcription factor (TF) genes expressed in the pain circuitry. TF genes are known to play central roles in cell type specification. In the mouse genome, about 1500 genes encode TFs that contain known DNA-binding motifs. In team together with Chuck Stiles lab, we have used in situ hybridization to map the spatial distribution of over 1200 TF genes in the developing mouse nervous system. By this systematic approach, we have gained a global view of TF genes expressed in nociceptors or pain relay neurons.

We are then performing genetic manipulations to study the functions of these candidate TF genes. Towards this end, we have identified two master regulators. First, we find that the runt domain transcription factor Runx1 controls the expression of a wide range of pain sensory channels and receptors. Behavior study showed that Runx1 is required for thermal and neuropathic pain. Second, we found that the Tlx class homeobox gene Tlx3 acts as a selector gene determining the excitatory over inhibitory cell fate in the dorsal horn pain relay station.

Several questions remain. First, many Runx1-dependent channels and receptors are expressed in a mutually exclusive manner, but the underlying mechanisms are unclear. Second, Runx1 expression defines a group of non-peptidergic nociceptors. Now we have a few candidate TF genes that might specify peptidergic nociceptors that are critical for inflammatory and cancer pain. Third, nociceptors undergo extensive phenotypic changes following nerve injury, which underlies the manifestation of neuropathic pain. We are performing a genome-scale screen for TFs that control injury-induced nociceptor plasticity. Fourth, we are developing genetic tools that allow us to address how distinct subtypes of dorsal horn excitatory neurons control pain behaviors. We hope these lines of efforts may eventually provide novel therapeutic targets for the treatment of pain.

Lab members
Yang Liu, Ph.D.
Chuan Cen, Ph.D.
Omar Abdel Samad, Ph.D.
Yi Xu, Ph.D
Fu-chia Yang, Ph.D.
Mila Komitova, Ph.D.