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Qiufu Ma, PhD


Researcher


Researcher

  • Associate Professor of Neurobiology, Harvard Medical School

Contact Information

  • Office Phone Number(617) 632-4594
  • Fax(617) 632-4595

Bio

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.

Recent Awards:

  • Pew Scholar 2000
  • SCBA Young Investigator Award 2001

Location

Dana-Farber Cancer Institute
450 Brookline Avenue
Smith 1022B
Boston MA, 02215
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Research

Regulation 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.

Lou S, Pan X, Huang T, Duan B, Yang FC, Yang J, Xiong M, Liu Y, Ma Q. Incoherent feed-forward regulatory loops control segregation of C-mechanoreceptors, nociceptors, and pruriceptors. J Neurosci. 2015 Apr 01; 35(13):5317-29.
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Chiu IM, Barrett LB, Williams EK, Strochlic DE, Lee S, Weyer AD, Lou S, Bryman GS, Roberson DP, Ghasemlou N, Piccoli C, Ahat E, Wang V, Cobos EJ, Stucky CL, Ma Q, Liberles SD, Woolf CJ. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity. Elife. 2014 Dec 19; 3.
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Duan B, Cheng L, Bourane S, Britz O, Padilla C, Garcia-Campmany L, Krashes M, Knowlton W, Velasquez T, Ren X, Ross S, Lowell BB, Wang Y, Goulding M, Ma Q. Identification of spinal circuits transmitting and gating mechanical pain. Cell. 2014 Dec 04; 159(6):1417-1432.
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Ma Q. Merkel cells are a touchy subject. Cell. 2014 Apr 24; 157(3):531-3.
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Yang FC, Tan T, Huang T, Christianson J, Samad OA, Liu Y, Roberson D, Davis BM, Ma Q. Genetic control of the segregation of pain-related sensory neurons innervating the cutaneous versus deep tissues. Cell Rep. 2013 Dec 12; 5(5):1353-64.
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Xu Y, Lopes C, Wende H, Guo Z, Cheng L, Birchmeier C, Ma Q. Ontogeny of excitatory spinal neurons processing distinct somatic sensory modalities. J Neurosci. 2013 Sep 11; 33(37):14738-48.
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Roberson DP, Gudes S, Sprague JM, Patoski HA, Robson VK, Blasl F, Duan B, Oh SB, Bean BP, Ma Q, Binshtok AM, Woolf CJ. Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons. Nat Neurosci. 2013 Jul; 16(7):910-8.
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Lou S, Duan B, Vong L, Lowell BB, Ma Q. Runx1 controls terminal morphology and mechanosensitivity of VGLUT3-expressing C-mechanoreceptors. J Neurosci. 2013 Jan 16; 33(3):870-82.
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Herriges JC, Yi L, Hines EA, Harvey JF, Xu G, Gray PA, Ma Q, Sun X. Genome-scale study of transcription factor expression in the branching mouse lung. Dev Dyn. 2012 Sep; 241(9):1432-53.
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Lopes C, Liu Z, Xu Y, Ma Q. Tlx3 and Runx1 act in combination to coordinate the development of a cohort of nociceptors, thermoceptors, and pruriceptors. J Neurosci. 2012 Jul 11; 32(28):9706-15.
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Liu T, Berta T, Xu ZZ, Park CK, Zhang L, Lü N, Liu Q, Liu Y, Gao YJ, Liu YC, Ma Q, Dong X, Ji RR. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest. 2012 Jun; 122(6):2195-207.
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Yu J, Valerius MT, Duah M, Staser K, Hansard JK, Guo JJ, McMahon J, Vaughan J, Faria D, Georgas K, Rumballe B, Ren Q, Krautzberger AM, Junker JP, Thiagarajan RD, Machanick P, Gray PA, van Oudenaarden A, Rowitch DH, Stiles CD, Ma Q, Grimmond SM, Bailey TL, Little MH, McMahon AP. Identification of molecular compartments and genetic circuitry in the developing mammalian kidney. Development. 2012 May; 139(10):1863-73.
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Ma Q. Population coding of somatic sensations. Neurosci Bull. 2012 Apr; 28(2):91-9.
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Mar L, Yang FC, Ma Q. Genetic marking and characterization of Tac2-expressing neurons in the central and peripheral nervous system. Mol Brain. 2012 Jan 24; 5:3.
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Wang T, Molliver DC, Jing X, Schwartz ES, Yang FC, Samad OA, Ma Q, Davis BM. Phenotypic switching of nonpeptidergic cutaneous sensory neurons following peripheral nerve injury. PLoS One. 2011; 6(12):e28908.
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Liu Y, Abdel Samad O, Zhang L, Duan B, Tong Q, Lopes C, Ji RR, Lowell BB, Ma Q. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron. 2010 Nov 04; 68(3):543-56.
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Ma Q. Labeled lines meet and talk: population coding of somatic sensations. J Clin Invest. 2010 Nov; 120(11):3773-8.
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Liu Y, Ma Q. Generation of somatic sensory neuron diversity and implications on sensory coding. Curr Opin Neurobiol. 2011 Feb; 21(1):52-60.
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Abdel Samad O, Liu Y, Yang FC, Kramer I, Arber S, Ma Q. Characterization of two Runx1-dependent nociceptor differentiation programs necessary for inflammatory versus neuropathic pain. Mol Pain. 2010 Jul 30; 6:45.
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Ross SE, Mardinly AR, McCord AE, Zurawski J, Cohen S, Jung C, Hu L, Mok SI, Shah A, Savner EM, Tolias C, Corfas R, Chen S, Inquimbert P, Xu Y, McInnes RR, Rice FL, Corfas G, Ma Q, Woolf CJ, Greenberg ME. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010 Mar 25; 65(6):886-98.
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Ma Q. RETouching upon mechanoreceptors. Neuron. 2009 Dec 24; 64(6):773-6.
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Fu H, Cai J, Clevers H, Fast E, Gray S, Greenberg R, Jain MK, Ma Q, Qiu M, Rowitch DH, Taylor CM, Stiles CD. A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development. J Neurosci. 2009 Sep 09; 29(36):11399-408.
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Gao YJ, Zhang L, Samad OA, Suter MR, Yasuhiko K, Xu ZZ, Park JY, Lind AL, Ma Q, Ji RR. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J Neurosci. 2009 Apr 01; 29(13):4096-108.
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Schüller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH, Ligon KL. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008 Aug 12; 14(2):123-34.
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Ma YC, Song MR, Park JP, Henry Ho HY, Hu L, Kurtev MV, Zieg J, Ma Q, Pfaff SL, Greenberg ME. Regulation of motor neuron specification by phosphorylation of neurogenin 2. Neuron. 2008 Apr 10; 58(1):65-77.
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Xu Y, Lopes C, Qian Y, Liu Y, Cheng L, Goulding M, Turner EE, Lima D, Ma Q. Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons. J Neurosci. 2008 Apr 09; 28(15):4037-46.
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Liu Y, Yang FC, Okuda T, Dong X, Zylka MJ, Chen CL, Anderson DJ, Kuner R, Ma Q. Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors. J Neurosci. 2008 Jan 02; 28(1):125-32.
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Woolf CJ, Ma Q. Nociceptors--noxious stimulus detectors. Neuron. 2007 Aug 02; 55(3):353-64.
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Schüller U, Kho AT, Zhao Q, Ma Q, Rowitch DH. Cerebellar 'transcriptome' reveals cell-type and stage-specific expression during postnatal development and tumorigenesis. Mol Cell Neurosci. 2006 Nov; 33(3):247-59.
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Ma Q. Transcriptional regulation of neuronal phenotype in mammals. J Physiol. 2006 Sep 01; 575(Pt 2):379-87.
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Chen CL, Broom DC, Liu Y, de Nooij JC, Li Z, Cen C, Samad OA, Jessell TM, Woolf CJ, Ma Q. Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain. Neuron. 2006 Feb 02; 49(3):365-77.
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Cheng L, Samad OA, Xu Y, Mizuguchi R, Luo P, Shirasawa S, Goulding M, Ma Q. Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes. Nat Neurosci. 2005 Nov; 8(11):1510-5.
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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 Dec 24; 306(5705):2255-7.
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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 May; 7(5):510-7.
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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 Nov 05; 23(31):9961-7.
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Qian Y, Shirasawa S, Chen CL, Cheng L, Ma Q. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Genes Dev. 2002 May 15; 16(10):1220-33.
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