Immunotherapy Center
Links:
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Research Program
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Faculty Laboratories:
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| Andrew Mellor, PhD |
| David Munn, MD |
| Pandelakis Koni, PhD |
| Michiko Shimoda, PhD |
| Affiliated Faculty: |
| Yukia He, MD, PhD |
Andrew L. Mellor Ph.D.
email: amellor@mcg.edu
Research Emphasis:
Our laboratory studies the regulation of T cell activation by antigen-presenting cells (dendritic cells) and regulatory T cells (Tregs). A major focus of the laboratory is the immunoregulatory role of tryptophan metabolism via the enzyme indoleamine 2,3-dioxygenase (IDO) expressed by antigen-presenting cells. Active projects include: (1) the role of IDO-expressing plasmacytoid dendritic cells in the regulation of immune responses; (2) the role of IDO in inflammation with emphasis on tumors, transplantation and auto-immune disease; (3) the role of IDO in Leishmania; (4) Treg activation by IDO. Goals are to develop new immunotherapies for clinical application based on fundamental research on IDO.
Laboratory members:
Phillip Chandler, PhD; Levi Makala PhD, David Kahler (Graduate Student); Burles Johnson III (MD/PhD Student); Doris McCool, Diane Addis, Anita Singh, Anita Singh, and Babak Baban, PhD.
Selected recent publications:
- Munn DH, Zhou M, Attwood JT, Bondarev I, Conway S, Marshall B, Brown C, Mellor AL. (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191-1193,
- Baban B, Hansen AM, Chandler PR, Manlapat A, Bingaman A, Kahler DJ, Munn DH, Mellor AL. (2005) A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation. Int Immunol. 17:909-19.
- Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH. (2005) Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN Type 1 signaling. J Immunol. 175:5601-5.
- Manlapat AK, Kahler DJ, Chandler PR, Munn DH, Mellor AL. (2007)
Cell-autonomous control of interferon type I expression by indoleamine 2,3-dioxygenase in regulatory CD19+ dendritic cells. Eur J Immunol 37:1064-71.
- Singh N, Chandler PR, Seki Y, Baban B, Takezaki M, Kahler DJ, Munn DH, Larsen CP, Mellor AL, Iwashima M. (2007) Role of CD28 in fatal autoimmune disorder in scurfy mice.
Blood. 2007;110:1199-206.
- Munn DH, Mellor AL. (2007) Indoleamine 2,3-dioxygenase and tumor-induced tolerance.
J Clin Invest.;117:1147-54. Review.
- Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest. 117:2570-82.
- Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Taylor PA, Mellor AL, Munn DH, Blazar BR. (2007) Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality. Blood. 2008:3257-65.
- Banerjee T, Duhadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ. (2008) A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3-dioxygenase. Oncogene. 27:2851-7.
- Keskin DB, Marshall B, Munn DH, Mellor AL, & Gearhart DA. (2007). Decreased protein nitration in macrophages that overexpress indoleamine 2,3 dioxygenase. Cell Mol Biol Lett 12:82-102.
- Mellor AL, Munn, DH. (2008) Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol. 74-80. Review
- Xu H, Oriss TB, Mingjian F, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, and Ray A. (2008) Indoleamine 2,3-Dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation Proc.Natl. Acad. Sci. (USA) , 105:6690-5.
- Mohib K, Wang S, Guan Q, Mellor AL, Sun H, Du C, Jevnikar AM. (2008) Indoleamine 2,3-dioxygenase (IDO) activity promotes renal ischemia reperfusion injury.
Am J Physiol Renal Physiol. (In Press)
- Harrington L, Srikanth CV, Antony R, Rhee SJ, Mellor AL, Shi HN, Cherayil BJ. (2008)
Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter colitis. Infect Immun. (In Press)