Junhao Mao PHD
Title Assistant Professor
Institution University of Massachusetts Medical School
Department Cancer Biology
Address University of Massachusetts Medical School
364 Plantation Street, LRB
Worcester MA 01605
Telephone 508-856-4149
Email
Other Positions
Institution UMMS - Graduate School of Biomedical Sciences
Department Cancer Biology
Narrative

Biography

Junhao Mao received his Ph.D. degree from the University of Rochester in 2002. He did his postdoctoral research at Harvard University from 2003 to 2008, where he was supported by the fellowships from Damon Runyon Cancer Research Foundation and Charles A. King Trust.   He joined the Department of Cancer Biology at the University of Massachusetts Medical School in fall 2008. Dr. Mao was also a recipient of the Charles H. Hood Foundation Child Health Research Award in 2009 and the American Cancer Society Research Scholar Award in 2011.   .

 

The Hedgehog (Hh) Signaling Pathway in Development and CancerJunhaoMao

The Hedgehog (Hh) signaling pathway, initially identified by its patterning activity in Drosophila embryos, plays many distinct roles in vertebrate development. Deregulation of Hh signaling has also been implicated in the etiology of a wide range of human cancers.  The overall goal of our research is to understand the mechanisms underlying molecular and cellular control of Hh signaling in mammalian organogenesis and tumorigenesis, with an emphasis on stem cell and progenitor cell function.  Our current efforts consist of two separate projects.

1.  Hh signaling, stem cells, and childhood rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a fast-growing, highly malignant skeletal muscle tumor and the most common soft-tissue sarcoma in children.  Genetic evidence from both human and mouse has demonstrated a clear link between RMS and Hh signaling.  To facilitate the study of Hh signaling in tumorigenesis, we have generated a novel, inducible somatic mouse model of Hh-related sporadic RMS.  Using a combination of cell biological and mouse transgenic approaches, we are now examining the role of Hh signaling in muscle stem cell transformation and tumor initiation.  We are also interested in exploring the possibility of Hh regulation of RMS cancer stem cells and in characterizing Gli-mediated transcriptional networks in Hh-related tumors. 

2.  Hh-mediated mesenchymal regulation in gastrointestinal development and cancer
Recent studies have revealed extensive involvement of Hh signaling in many tumors arising from the gastrointestinal (GI) tract, including carcinomas of the stomach, colon, and pancreas.  Despite the significance of Hh in GI tumorigenesis, the exact function of Hh signaling in GI development remains unclear.  We have identified a primary role for Hh proteins as mitogens for mesenchymal progenitor cells in the developing gut.  We will examine the genetic and cellular interactions between the Hh signaling pathway and other critical pathways, such as BMP, Notch, IGF and Wnt in GI mesenchymal cell growth and differentiation.   Such interactions might form the developmental and mechanistic basis for Hh participation in GI tumorigenesis.

Publications
1. Goel HL, Pursell B, Chang C, Shaw LM, Mao J, Simin K, Kumar P, Kooi CW, Shultz LD, Greiner DL, Norum JH, Toftgard R, Kuperwasser C, Mercurio AM. GLI1 regulates a novel neuropilin-2/a6ß1 integrin based autocrine pathway that contributes to breast cancer initiation. EMBO Mol Med. 2013 Feb 21.
  View in: PubMed
 
2. Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, Yang Y, Li S, Tang K, Chen H, Powell A, Itan Y, Fuller D, Lohmueller J, Mao J, Schachar A, Paymer M, Hostetter E, Byrne E, Burnett M, McMahon AP, Thomas MG, Lieberman DE, Jin L, Tabin CJ, Morgan BA, Sabeti PC. Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell. 2013 Feb 14; 152(4):691-702.
  View in: PubMed
 
3. Rajurkar M, De Jesus-Monge WE, Driscoll DR, Appleman VA, Huang H, Cotton JL, Klimstra DS, Zhu LJ, Simin K, Xu L, McMahon AP, Lewis BC, Mao J. The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis. Proc Natl Acad Sci U S A. 2012 Apr 24; 109(17):E1038-47.
  View in: PubMed
 
4. Kim TH, Kim BM, Mao J, Rowan S, Shivdasani RA. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development. 2011 Aug; 138(15):3225-33.
  View in: PubMed
 
5. Kaneko S, Chen X, Lu P, Yao X, Wright TG, Rajurkar M, Kariya K, Mao J, Ip YT, Xu L. Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci U S A. 2011 Jul 5; 108(27):11127-32.
  View in: PubMed
 
6. Mao J, Kim BM, Rajurkar M, Shivdasani RA, McMahon AP. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development. 2010 May; 137(10):1721-9.
  View in: PubMed
 
7. Hofmann I, Stover EH, Cullen DE, Mao J, Morgan KJ, Lee BH, Kharas MG, Miller PG, Cornejo MG, Okabe R, Armstrong SA, Ghilardi N, Gould S, de Sauvage FJ, McMahon AP, Gilliland DG. Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis. Cell Stem Cell. 2009 Jun 5; 4(6):559-67.
  View in: PubMed
 
8. Mao J, McGlinn E, Huang P, Tabin CJ, McMahon AP. Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb. Dev Cell. 2009 Apr; 16(4):600-6.
  View in: PubMed
 
9. 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.
  View in: PubMed
 
10. Kim BM, Miletich I, Mao J, McMahon AP, Sharpe PA, Shivdasani RA. Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen. Development. 2007 Oct; 134(20):3603-13.
  View in: PubMed
 
11. Kim BM, Mao J, Taketo MM, Shivdasani RA. Phases of canonical Wnt signaling during the development of mouse intestinal epithelium. Gastroenterology. 2007 Aug; 133(2):529-38.
  View in: PubMed
 
12. Mao J, Ligon KL, Rakhlin EY, Thayer SP, Bronson RT, Rowitch D, McMahon AP. A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res. 2006 Oct 15; 66(20):10171-8.
  View in: PubMed
 
13. Mao J, Barrow J, McMahon J, Vaughan J, McMahon AP. An ES cell system for rapid, spatial and temporal analysis of gene function in vitro and in vivo. Nucleic Acids Res. 2005; 33(18):e155.
  View in: PubMed
 
14. Zhang Y, Wang Y, Li X, Zhang J, Mao J, Li Z, Zheng J, Li L, Harris S, Wu D. The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd. Mol Cell Biol. 2004 Jun; 24(11):4677-84.
  View in: PubMed
 
15. Jeong J, Mao J, Tenzen T, Kottmann AH, McMahon AP. Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia. Genes Dev. 2004 Apr 15; 18(8):937-51.
  View in: PubMed
 
16. Weaver C, Farr GH, Pan W, Rowning BA, Wang J, Mao J, Wu D, Li L, Larabell CA, Kimelman D. GBP binds kinesin light chain and translocates during cortical rotation in Xenopus eggs. Development. 2003 Nov; 130(22):5425-36.
  View in: PubMed
 
17. Mao J, Maye P, Kogerman P, Tejedor FJ, Toftgard R, Xie W, Wu G, Wu D. Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1. J Biol Chem. 2002 Sep 20; 277(38):35156-61.
  View in: PubMed
 
18. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002 May 16; 346(20):1513-21.
  View in: PubMed
 
19. Mao J, Wu D. Functional interaction of G alpha 13 with p115RhoGEF determined with transcriptional reporter system. Methods Enzymol. 2002; 345:404-10.
  View in: PubMed
 
20. Li L, Mao J, Sun L, Liu W, Wu D. Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J Biol Chem. 2002 Feb 22; 277(8):5977-81.
  View in: PubMed
 
21. Mao J, Wang J, Liu B, Pan W, Farr GH, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 2001 Apr; 7(4):801-9.
  View in: PubMed
 
22. Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J. Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway. Nat Struct Biol. 2000 Dec; 7(12):1178-84.
  View in: PubMed
 
23. Yuan H, Mao J, Li L, Wu D. Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation. J Biol Chem. 1999 Oct 22; 274(43):30419-23.
  View in: PubMed
 
24. Li L, Yuan H, Weaver CD, Mao J, Farr GH, Sussman DJ, Jonkers J, Kimelman D, Wu D. Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. EMBO J. 1999 Aug 2; 18(15):4233-40.
  View in: PubMed
 
25. Li L, Yuan H, Xie W, Mao J, Caruso AM, McMahon A, Sussman DJ, Wu D. Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells. J Biol Chem. 1999 Jan 1; 274(1):129-34.
  View in: PubMed
 
26. Mao J, Yuan H, Xie W, Wu D. Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein alpha subunit Galpha13. Proc Natl Acad Sci U S A. 1998 Oct 27; 95(22):12973-6.
  View in: PubMed
 
27. Mao J, Yuan H, Xie W, Simon MI, Wu D. Specific involvement of G proteins in regulation of serum response factor-mediated gene transcription by different receptors. J Biol Chem. 1998 Oct 16; 273(42):27118-23.
  View in: PubMed
 
28. Mao J, Xie W, Yuan H, Simon MI, Mano H, Wu D. Tec/Bmx non-receptor tyrosine kinases are involved in regulation of Rho and serum response factor by Galpha12/13. EMBO J. 1998 Oct 1; 17(19):5638-46.
  View in: PubMed
 
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Keyword
Last Name
Institution
    
 
 
 
Keywords   
Hedgehog Proteins
DNA-Binding Proteins
Proteins
Zebrafish Proteins
Signal Transduction
See all (190) keywords
Co-Authors  
Greiner, Dale
Ip, Yicktung
Shultz, Leonard
Simin, Karl
Zhu, Lihua
See all (9) people
Physical Neighbors  
Bergmann, Andreas
Goel, Hira
Kelliher, Michelle
Cantor, Sharon
Lyle, Stephen

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