Qiufu Ma, PhD
Office phone: 617-632-4594
Preferred contact method: email
Area of ResearchRegulation of Trigeminal Neuron Differentiation and Axonal Projection
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Ma received his PhD from the University of California, Los Angeles, in 1994, and his postdoctoral training in developmental neurobiology at the California Institute of Technology, where he isolated a transcriptional factor that functions as a mammalian neuronal fate-determination factor. He joined DFCI in 1999 and became an associate professor in 2004.
- SCBA Young Investigator Award, 2001
- Pew Scholar, 2000
ResearchRegulation of Trigeminal Neuron Differentiation and Axonal Projection
We are interested in investigating the molecular mechanisms that govern the formation and function of pain sensory neurons. In mammals, painful 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. Under pathological conditions - such as inflammation, nerve injuries, or cancer cell invasion - nociceptors can be sensitized, resulting in persistent chronic pain disorders. Few effective medicines are available for neuropathic pain, and over 45% of cancer patients in the United States suffer untreatable pain. A major goal of our research is to understand how distinct classes of nociceptors are specified during development and how nociceptors come to be sensitized during pathological conditions, with the ultimate goal of developing new therapeutic targets for pain treatment.
To address these questions, we have taken a systematic approach to identifying 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 collaboration with the laboratory of Dr. Charles Stiles, we have used in situ hybridization to map the spatial distribution of over 1200 TF genes in the developing mouse nervous system. This genome-scale screen allows us to gain a global view of TF genes expressed in nociceptors.
We also perform genetic manipulations to study the functions of these candidate TF genes in pain sensory neuron development. Towards this end, we have identified two key regulators. First, we found that the runt domain transcription factor Runx1 controls the expression of a wide range of pain sensory channels and receptors. Behavior studies showed that Runx1 is required selectively for thermal and neuropathic pain. Second, we found that the Tlx class homeobox gene Tlx3 determines the excitatory neurotransmitter phenotype in pain relay neurons in the dorsal horn of the spinal cord.
The genome-scale TF analysis also allows us to address several remaining questions. 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; we now have a few candidate TF genes that may specify peptidergic nociceptors, which are known to be critical for inflammatory and cancer pain. Third, we will screen small chemicals that block the expression or function of Runx1 and other TFs, with the goal of developing new therapeutic targets for pain treatment.
- * Cheng L, Abdel Samad O, Xu Y, Mizuguchi RM, Luo P, Goulding M, Ma Q. Lbx1 and Tlx3 act as opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes. Nat Neurosci 2005. In press.
- Gray PA, Fu H, Luo P, Zhao Q, Yu J, Ferrari A, Tenzen T, Yuk DI, Tsung EF, Cai Z, Alberta JA, Cheng LP, Liu Y, Stenman JM, Valerius MT, Billings N, Kim HA, Greenberg ME, McMahon AP, Rowitch DH, Stiles CD, Ma Q. Mouse brain organization revealed through direct genome-scale TF expression analysis. Science 2004;306:2255-7.
- Cheng L, Arata A, Mizuguchi R, Qian Y, Karunaratne A, Gray PA, Arata S, Shirasawa S, Bouchard M, Luo P, Chen CL, Busslinger M, Goulding M, Onimaru H, Ma Q. Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nat Neurosci 2004;7:510-7.
- Cheng L, Chen CL, Luo P, Tan M, Qiu M, Johnson R, Ma Q. Lmx1b, Pet-1 and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype. J Neurosci 2003;23:9961-7.
- Abdel-Samad, Omar, PhD
- Cen, Chuan, PhD
- Liu, Yang, PhD
- Xu, Yi, MD, PhD
- Yang, Fu-Chia, PhD