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Qiufu Ma, Ph.D.

Associate Professor of Neurobiology

Dana Farber Cancer Institute
Cancer Biology/MA, Smith 1022
44 Binney St
Boston, MA 02115
Telephone: 617-632-4594
Email: Qiufu_MA@dfci.harvard.edu
Predocs: 0 Postdocs: 6 Completed PhD's: 0

 Qiufu MA

We are interested in investigating the molecular mechanisms underlying the formation of pain sensory 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 underlie the initial reaction to noxious thermal, chemical and mechanical stimuli. Noxious sensory information is relayed to the brain through the dorsal horn of the spinal cord. A major goal of our research is to understand how distinct classes of nociceptors and spinal relay neurons are specified.

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 dorsal horn neurons.

We are then performing genetic manipulations to study the functions of these candidate TF genes. Towards this end, we have identified two key 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 selectively for thermal and neuropathic pain, but not for mechanical 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 of the spinal cord.

The genome scale TF analysis puts us in a position to address several remaining outstanding questions. First, many Runx1-dependent channels and receptors are expressed in a mutually exclusive manner, but the underlying mechanisms are completely unclear. Second, Runx1 expression defines a group of non-peptidergic nociceptors necessary for thermal and neuropathic pain. Now we have a few candidate TF genes that might specify peptidergic nociceptors, which are likely critical for mechanical and inflammatory pain. Third, we have also identified a number of TF genes that may be responsible for the generation of dorsal horn relay neuron diversity. Forth, pain management remains a big medical problem. The identification of key regulators may eventually provide novel therapeutic targets to treat chronic pain disorders.

 

References

  • Xu, Y, Lopes, C, Qian, Y, Liu, Y, Cheng, L, Goulding, M, Turner, E, Lima, D, and Ma, Q. (2007) Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons (submitted)
  • Liu, Y, Yang, F, Okuda, T, Dong, X, Zylka-M, Chen, C, and Ma, Q. (2007) Mechanisms of compartmentalized expression of nociceptive sensory receptors (submitted)

  • Woolf, C. and Ma, Q. (2007) Nociceptors – noxious stimulus detectors. Neuron 55:353-64.

  • Chen, C, Broom D, Liu, Y, de Nooij, J, Li, Z., Cen, C.,