Research Faculty


NEED PHOTO

Yaping Sun, M.D., Ph.D.
Research Investigator

yapings@umich.edu
Phone: 734-615-7127

Campus address:
University of Michigan Comprehensive Cancer Center
Room 3420/SPC 5934
1500 E Medical Center Dr., Ann Arbor, MI 48109

Research Interests

Histone deacetylase (HDAC) inhibition modulates immune function, but the mechanisms by which HDAC inhibition  modulates immune responses remain largely unknown. STAT-3 is a transcription factor shown to negatively regulate  DC functions by  promoting the transcription of IDO. These findings demonstrate a novel functional role for posttranslational modification of STAT-3 through acetylation and provide mechanistic insights into HDAC inhibition-mediated immunoregulation.

As an important transcription factor, STAT3, once acetylated  and activated, may have more targets which impact immunomodulation. We are pursuing the genome-wide targets for activated-STAT3 and exploring its regulatory network  in immune system, together with in vitro and in vivo functional studies.

We are still continuing to identify the targets by pan or specific HDAC inhibition and to explore the details for the overall and differential acetylated protein pools (acetylomes). The identified proteins will be further studied for their differentially functional roles in immunomodulation.   

miRNAs are the short noncoding single-strand RNA species found in a wide variety of organisms. The role of miRNAs in cell fate decision linked to proliferation, differentiation and apoptosis. The importance of miRNAs on immune system development and response has only been recently become evident.  miRNA control has emerged as a critical regulatory principle in the mammalian immune system. We recently found a navel microRNA, miR-142-3p, which is heamatopoietic system specific, and targets immune system by either degrading mRNA or inhibiting translation of particular cytokine to regulate immune response. We have generated gene KO mice to study its role  in BMT and immune response. Moreover, we have produced an atlas for hematopoietic-specific microRNAs by a novel CLIP-Chip technology to identify allogeneic specific miRNAs in T cells. This work will get deeper insight into the regulatory function of these hematopoietic-specific miRNAs in T cells in vitro and in vivo. 

 

Education and Training

1982 M.D., Anhui Medical University, China
1987 M.S., Biochemistry, Jiangxi Medical College, China
1995 Ph.D., Biochemistry and Molecular Biology, Shanghai Medical University, China
1998-2000 Postdoc Training, Department of Pharmaceutical Sciences, Texas Technological University, Molecular Endocrinology and Cancer Biology
2001-2006 Postdoc Training, Department of Biological Science and Biochemistry, University of Toledo, Molecular BIology of Cytokine and Innate Immunity
2006-2010 Postdoc Training, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, GVHD/GVL and Immunomodulation

Honors & Awards

1994 Outstanding graduate student award, Shanghai Medical University
1994 First Place Award - Outstanding presentation at National Medical Science Academic Meeting, Beijing, China
1997 Outstanding Research Award, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China


Selected Publications (2008-present)

Reddy P, Sun Y, Toubai T, Duran-Struuck R, Clouthier SG, Weisiger E, Maeda Y, Tawara I, Krijanovski O, Gatza E, Liu C, Malter C, Mascagni P, Dinarello CA, Ferrara JL. Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice. J Clin Invest, 2008 Jul; 118(7):2562-2573. (PMID 18568076)  PMC 2430497.

Sun Y
, Chin YE, Weisiger E, Malter C, Tawara I, Toubai T, Gatza E, Mascagni P, Dinarello CA, Reddy P. Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3. J Immunol, 2009 May 15; 182(10):5899-5903. (PMID 19414739).

Paczesny S, Hanauer D, Sun Y, Reddy P.  New perspectives on the biology of acute GVHD. Bone Marrow Transplant, 2010 Jan; 45(1):1-11. (PMID 19946340).

Toubai T, Malter C, Tawara I, Liu C, Nieves E, Lowler KP, Sun Y, Reddy P. Immunization with host-type CD8{alpha}+ dendritic cells reduces experimental acute GVHD in an IL-10-dependent manner. Blood, 2010 Jan 21; 115(3):724-735. (PMID 19965670)  PMC 2810989.

Tawara I, Shlomchik WD, Jones A, Zou W, Nieves E, Liu C, Toubai T, Duran-Struuck R, Sun Y, Clouthier SG, Evers R, Lowler KP, Levy RB, Reddy P.  A crucial role for host APCs in the induction of donor CD4+CD25+ regulatory T cell-mediated suppression of experimental graft-versus-host disease. J Immunol, 2010 Oct 1; 185(7):3866-3872. (PMID 20810991) PMC 2981818.

Tawara I, Koyama M, Liu C, Toubai T, Thomas D, Evers R, Chockley P, Nieves E, Sun Y, Lowler KP, Malter C, Nishimoto N, Hill GR, Reddy P.  Interleukin-6 modulates graft-versus-host responses after experimental allogeneic bone marrow transplantation. Clin Cancer Res, 2011 Jan 1; 17(1):77-88. (PMID 21047980)  PMC 3058832.

Sun Y
, Varambally S, Maher CA, Cao Q, Chockley P, Toubai T, Malter C, Nieves E, Tawara I, Wang Y, Ward PA, Chinnaiyan A, Reddy P.  Targeting of microRNA-142-3p in dendritic cells regulates endotoxin-induced mortality. Blood, 2011 Jun 9; 117(23):6172-6183. (PMID 21474672)  PMC 3122940.

Toubai T, Sun Y, Tawara I, Friedman A, Liu C, Evers R, Nieves E, Malter C, Chockley P, Maillard I, Winandy S, Reddy P.  Ikaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease. Blood, 2011 Jul 7; 118(1):192-204. (PMID 21471527) PMC 3139384.

Tawara I, Nieves E, Liu C, Evers R, Toubai T, Sun Y, Alrubaie M, Reddy P.  Host basophils are dispensable for induction of donor T helper 2 cell differentiation and severity of experimental graft-versus-host disease. Biol Blood Marrow Transplant, 2011 Dec; 17(12):1747-1753. (PMID 21871863)  PMC 3220796.

Tawara I, Sun Y, Lewis EC, Toubai T, Evers R, Nieves E, Azam T, Dinarello CA, Reddy P. Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation. Proc Natl Acad Sci U S A, 2012 Jan 10; 109(2):564-569. (PMID 22203983)  PMC 3258603.

Tawara I, Sun Y, Liu C, Toubai T, Nieves E, Evers R, Alrubaie M, Mathewson N, Tamaki H, Reddy P. Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease. J Leukoc Biol, 2012 Apr; 91(4):667-675. (PMID 22262800)  PMC 3317273.

Toubai T, Tawara I, Sun Y, Liu C, Nieves E, Evers R, Friedman T, Korngold R, Reddy P. Induction of acute GVHD by sex-mismatched H-Y antigens in the absence of functional radiosensitive host hematopoietic-derived antigen-presenting cells. Blood, 2012 Apr 19; 119(16):3844-3853. (PMID 22101894)  PMC 3335388.

Tawara I, Liu C, Tamaki H, Toubai T, Sun Y, Evers R, Nieves E, Mathewson N, Nunez G, Reddy P. Influence of donor microbiota on the severity of experimental graft-versus-host-disease. Biol Blood Marrow Transplant, 2013 Jan; 9(1):164-168. (PMID 22982686) PMC 3529780.

Toubai T, Sun Y, Luker G, Liu J, Luker KE, Tawara I, Evers R, Liu C, Mathewson N, Malter C, Nieves E, Choi S, Murphy KM, Reddy P.  Host derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood, 2013 Mar 21. (PMID 23520337).

Sun Y
, Sun J, Tomomi T, Nieves E, Mathewson N, Tamaki H, Evers R, Reddy P. PU.1-Dependent Transcriptional Regulation of miR-142 Contributes to Its Hematopoietic Cell-Specific Expression and Modulation of IL-6. J Immunol, 2013 Apr 15; 190(8):4005-4013. (PMID 23509362)  PMC 3619529.