1120 15th Street CN 4141 Augusta, GA 30912 Office: (706) 721-7141 Appointments: (706) 721-8733 E-mail: dmunn@georgiahealth.edu

Munn, David, M.D.

David Munn, MD, pediatric oncologist, in his office at The GRU Cancer Center.

Munn, David, M.D.
Senior Advisor to the Cancer Center Director

Member, Cancer Immunology, Inflammation and Tolerance Program
Associate Professor of Medicine
Professor of Pediatrics
Professor of Pathology
Professor of Cellular Biology and Anatomy
Professor of Biochemistry and Molecular Biology
Professor of Graduate Studies
GRU Cancer Center

 

1120 15th Street, CN 4141
Phone: (706) 721-8735
DMUNN@ gru.edu

IFL Link | PubMed Link

Current Research

His current research focuses on tumor immunology, and molecular mechanisms of immune suppression and tolerance. Dr. Munn’s laboratory studies the regulation of T cell activation by tolerogenic dendritic cells and regulatory T cells (Tregs) in the setting of cancer.  A major focus of the laboratory is the immunoregulatory role of tryptophan metabolism via the enzyme indoleamine 2,3-dioxygenase (IDO).  Dr. Munn’s research is supported by grants from the National Cancer Institute, and through charitable endowments for pediatric oncology research.

Active projects include:

  • Preclinical and basic-science studies of the role of IDO-expressing plasmacytoid dendritic cells (pDCs) in tumor immunology, with an emphasis on how these tolerogenic antigen-presenting cells suppress anti-tumor immune responses via IDO and downstream pathways (AhR and GCN2).
  • Clinical/translational strategies (Phase I and II clinical trials) designed to enhance
    anti-tumor immune responses using IDO-inhibitor drugs.
  • Mechanistic studies of strategies to enhance anti-tumor immune response using vaccines
    in combination with inhibitors of immunosuppressive pathways (IDO, PD-1 and CTLA-4).
  • Control of regulatory T cell (Treg) suppressor activity by IDO, and functional activity of CD4+ helper T cells and reprogrammed Tregs.

Key References

Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase pathway: effect on Foxp3+ Tregs and cancer. In Prendergast GC and Jaffee EM (Eds) Cancer Immunotherapy: Immune Suppression and Tumor Growth, 2nd Edition. Elsevier (2013)

Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 34:137-143 (2013)

Sharma MD, Huang L, Choi JH, Lee EJ, Wilson JM, Lemos H, Pan F, Blazar BR, Pardoll DM, Mellor AL, Shi H, Munn DH. An inherently bi-functional subset of Foxp3+ Treg/T-helper cells is controlled by the transcription factor Eos. Immunity 38:998-1012 (2013)

Holmgaard RB, Zamarin D, Munn DH, Wolchok JD and Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in anti-tumor T cell immunotherapy targeting CTLA-4. J Exp Med 210:1389-1402 (2013)

Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity. 2010 33:942-54

Hou DY, Muller AJ, Sharma M, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC, Munn DH. Inhibition of IDO in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with anti-tumor responses. Cancer Res 2007;67:792-801.

Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 2007;117:2570-82.

Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 2005;22:633-42.

Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 2004;114:280-90.

Munn DH, Sharma M, Lee J, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr , Mellor AL. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 2002;297:1867-70.

Munn DH, Zhou M, Attwood JT, Bondarev I, Conway S, Marshall B, Brown C, Mellor AL. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281:1191-93.

 

Grants (selected)

  • National Cancer Institute: “IDO-expressing immunoregulatory dendritic cells” 2003-2019, D. Munn, PI
  • National Cancer Institute: “Role of IDO malignancy” 2002-2017, D. Munn, PI
  • National Cancer Institute: “IDO-mediated immune regulation in established tumors” 2005-2014, D. Munn, PI
  • National Institutes of Health: “Manipulating natural host immunoregulation via IDO during viral infection” 2009-2014, D. Munn, co-I
  • Corn Foundation: “IDO in pediatric malignancies” 2005-2014 / D. Munn, PI

Grant information is updated quarterly.

 

Publications (selected)

member of editorial board:

  • Cancer Immunology Research
  • Journal for Immunotherapy of Cancer (JITC)

editorial reviewer:

  • Science
  • Immunity
  • Journal of Clinical Investigation
  • Blood
  • Journal of Experimental Medicine
  • Nature Immunology
  • Nature Medicine
  • Journal of Immunology
  • FASEB Journal

Ascierto PA, Munn DH, Palucka AK, Sondel PM. Highlights and Summary of the 28th Annual Meeting of the Society for Immunotherapy of Cancer. J Immunotherapy Cancer 2:15 (2014)

Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V. Regulation of colonic inflammation and carcinogenesis by Gpr109a, a G-protein-coupled receptor for niacin and the commensal metabolite butyrate. Immunity 40:128-139 (2014)

Liu H, Huang L, Bradley J, Liu K, Bardhan K, Ron D, Mellor AL, Munn DH, McGaha TL. GCN2-dependent metabolic stress is essential for endotoxemic cytokine induction and pathology. Mol Cell Biol 34:428-38 (2014)

Hong Y, Peng Y, Guo SZ, Guevara-Patino J, Pang J, Butterfield LH, Mivechi N, Munn DH, Bartlett DL, He Y. Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma. Hepatology 59:1448–1458 (2014)

Ravishankara B, Shindea , Liu H, Chaudharya K, Bradleya J, Lemosa HP, Chandler P, Tanaka M, Munn DH, Mellor AL, McGaha TL. Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance. Proc Nat Acad Sci 111:4215-4220 (2014)

Sharma MD, Huang L, Choi JH, Lee EJ, Wilson JM, Lemos H, Pan F, Blazar BR, Pardoll DM, Mellor AL, Shi H, Munn DH. An inherently bi-functional subset of Foxp3+ Treg/T-helper cells is controlled by the transcription factor Eos. Immunity 38:998-1012 (2013)

Holmgaard RB, Zamarin D, Munn DH, Wolchok JD and Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in anti-tumor T cell immunotherapy targeting CTLA-4. J Exp Med 210:1389-1402 (2013)

Huang L, Li L, Lemos H, Chandler PR, Pacholczyk G, Baban B, Barber GN, Hayakawa Y, McGaha TL, Ravishankar B, Munn DH, Mellor AL. Cutting Edge: DNA sensing via the Stimulator of Interferon Genes (STING) adaptor in myeloid dendritic cells induces potent immune regulation via IDO1. J Immunol 191:3509-3513 (Aug., 2013)

Xiao H, Peng Y, Hong Y, Huang L, Guo ZS, Bartlett DL, Fu N, Munn DH, Mellor A, He Y. Local Administration of TLR Ligands Rescues the Function of Tumor-Infiltrating CD8 T Cells and Enhances the Antitumor Effect of Lentivector Immunization. J Immunol 190:5866-73 (2013)

Munn DH. Blocking IDO activity to enhance anti-tumor immunity. Frontiers Biosci 4:734-745 (2012)

Medzhitov R, Shevach EM, Trinchieri G, Mellor AL, Munn DH*, Gordon S, Libby P, Hansson GK, Shortman K, Dong C, Gabrilovich D, Gabrysova L, Howes A, O’Garra A. Highlights of 10 years of immunology in Nature Reviews Immunology. Nat Rev Immunol 11:693-702 (2011)

Ding ZC, Huang L, Blazar B, Yagita H, Mellor AL, Munn DH, Zhou G. Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy. Blood 120:2229-2239 (Sep., 2012)

Metz R, Rust S, DuHadaway JB, Mautino MR, Munn DH, Vahanian NN, Link CJ, Prendergast GC. IDO activation inhibits a tryptophan sufficiency signal needed to stimulate mTOR: a novel IDO effector pathway targeted by D-1-methyl-tryptophan. Oncoimmunology 1:1460-1468 (Dec. 2012)

Pei L, Choi JH, Liu J, Lee EJ, McCarthy B, Wilson JM, Speir E, Awan F, Tae H, Arthur G, Schnabel JL, Taylor KH, Wang X, Xu D, Ding HF, Munn DH, Caldwell C, Shi H. Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia. Epigenetics 7:567-578 (Jan., 2012)

Ravishankar B, Liu H, Shinde R, Chandler P, Baban B, Tanaka M, Munn DH, Mellor AL, Karlsson MCI, McGaha TL. Tolerance to apoptotic cells is regulated by indoleamine 2,3 dioxygenase. Proc Nat Acad Sci 109:3909-3914 (Feb., 2012)

Huang L, Lemos HP, Li L, Li M, Chandler PR, Baban B, McGaha TL, Ravishankar B, Lee JR, Munn DH, Mellor AL. Engineering DNA nanoparticles as immunomodulatory reagents that activate regulatory T cells. J Immunol 188:4913-4920 (May, 2012)

Hong Y, Peng Y, Mi M, Munn DH, Wang GQ, He Y.   Lentivector expressing HBsAg and immunoglobulin Fc fusion antigen induces potent immune responses and results in seroconversion in HBsAg transgenic mice. Vaccine 29:3909–3916 (Mar., 2011)

Baban B, Chandler PR, Johnson BA, Li M, Francisco LM, Sharpe AH, Blazar BR, Munn DH, Mellor AL. Physiologic control of regulatory T cell activation by dendritic cells expressing IDO. J Immunol 187: 2329–2335 (Aug., 2011)

Divanovic S, Sawtell NM, Trompette A, Warning JI, Dias A, Cooper AM, Yap GS, Arditi M, Shimada K, DuHadaway JB, Prendergast GC, Basaraba RJ, Mellor AL, Munn DH, Aliberti J, Karp CL. Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. J Inf Dis 205:152-161 (Jan., 2012)

Mellor AL, Munn DH. Physiologic control of the functional status of Foxp3+ regulatory T cells. J Immunol 186:4535-4540 (2011).

Makala LH, Baban B, Lemos H, El-Awady AR, Chandler PR, Hou DY, Munn DH, Mellor AL. Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression. J Infect Dis. 2011 Mar;203(5):715-25.

Antonov AS, Antonova GN, Munn DH, Mivechi N, Lucas R, Catravas JD, Verin AD. alphaVbeta3 Integrin Regulates Macrophage Inflammatory Responses via PI3-kinase/Akt-dependent NF-kappaB activation. J Cell Physiol. 2011 Feb;226(2):469-76.

Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity. 2010 Dec 14;33(6):942-54.

Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, Taylor PA, Panoskaltsis-Mortari A, Serody JS, Munn DH, Tolar J, Ochoa AC, Blazar BR. Bone marrow myeloid-derived suppressor cells (MDSC) inhibit graft-versus-host (GVHD) disease via an arginase-1 dependent mechanism that is upregulated by IL-13. Blood. 2010 Dec 16;116(25):5738-47.

Zhou Q, Xiao H, Liu Y, Peng Y, Hong Y, Yagita H, Chandler P, Munn DH, Mellor A, Fu N, He Y. Blockade of programmed death-1 pathway rescues the effector function of tumor-infiltrating T cells and enhances the antitumor efficacy of lentivector immunization. J Immunol. 2010 Nov 1;185(9):5082-92.

Zhou Q, Munger ME, Highfill SL, Tolar J, Weigel BJ, Riddle M, Sharpe AH, Vallera DA, Azuma M, Levine BL, June CH, Murphy WJ, Munn DH, Blazar BR. Program death-1 (PD-1) signaling and regulatory T cells (Tregs) collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes (CTLs) in advanced acute myeloid leukemia (AML). Blood. 2010 Oct 7;116(14):2484-93.

Metz R, Duhadaway JB, Rust S, Munn DH, Muller AJ, Mautino M, Prendergast GC. Zinc protoporphyrin IX stimulates tumor immunity by disrupting the immunosuppressive enzyme indoleamine 2,3-dioxygenase. Mol Cancer Ther. 2010 Jun;9(6):1864-71.

Johnson BA 3rd, Kahler DJ, Baban B, Chandler PR, Kang B, Shimoda M, Koni PA, Pihkala J, Vilagos B, Busslinger M, Munn DH, Mellor AL. B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10644-8.

Ding ZC, Blazar BR, Mellor AL, Munn DH, Zhou G. Chemotherapy rescues tumor-driven aberrant CD4+ T cell differentiation and restores an activated polyfunctional helper phenotype. Blood 115: 2397 – 2406 (2010)

Munn, D. H. Lineage-specific transcription factors in unexpected places. Eur J Immunol. 2010 Jan 26, 40: 315–317.

Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+ Tregs to TH17 -like cells in tumor-draining lymph nodes. Blood 113:6102-6111 (Jun, 2009).

Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Mellor AL, Munn DH, Blazar BR. Inducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. Blood. 2009 Dec 3;114(24):5062-70.

Zhou Q, Bucher C, Munger ME, Highfill SL, Tolar J, Munn DH, Levine BL, Riddle M, June CH, Vallera DA, Weigel BJ, Blazar BR. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 2009 Oct 29;114(18):3793-802.

Munn DH. Th17 cells in ovarian cancer. Blood. 2009 Aug 6;114(6):1134-5.

Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol. 2009 Aug 15;183(4):2475-83.

Chung DJ, Rossi M, Romano E, Ghith J, Yuan J, Munn DH, Young JW. Indoleamine 2,3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells. Blood. 2009 Jul 16;114(3):555-63.

Liu Y, Peng Y, Mi M, Guevara-Patino J, Munn DH, Fu N, He Y. Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice. J Immunol. 2009 May 15;182(10):5960-9.

Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009 Jun 11;113(24):6102-11.

Kim YH, Choi BK, Kang WJ, Kim KH, Kang SW, Mellor AL, Munn DH, Kwon BS. IFN-gamma-indoleamine-2,3 dioxygenase acts as a major suppressive factor in 4-1BB-mediated immune suppression in vivo. J Leukoc Biol. 2009 May;85(5):817-25.

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Pendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2, 3 dioxygenase. Proc Nat Acad Sci 104:17073-17078 (2008).

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Natl Acad Sci USA. 2008 Nov 4;105(44):17073-8.

Chen W, Liang X, Peterson AJ, Munn DH, Blazar R. The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol. 2008;181:5396-404.

Xu H, Oriss TB, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, Ray A. A Role for Indoleamine 2,3-Dioxygenase in Lung Dendritic Cell Activation in Response to Allergens Impacting Allergic Airways Disease FASEB J. 2008 22: 670.9

Manches O, Munn DH, Fallahi A, Lifson J, Chaperot L, Plumas J, Bhardwaj N. HIV-activated plasmacytoid dendritic cells induce regulatory T cells through an indoleamine 2,3 dioxygenase dependent mechanism. J Clin Invest. 2008;118:3431-9.

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Nat Acad Sci. 2008;104:17073-8.

Manches O, Munn DH, Fallahi A, Lifson J, Chaperot L, Plumas J and Bhardwaj N. HIV-activated plasmacytoid dendritic cells induce regulatory T cells through an indoleamine 2,3 dioxygenase dependent mechanism. J Clin Invest. 2008;118:3431-9.

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC and Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Nat Acad Sci. 2008;104:17073-8.

Karunakaran S, Umapathy NS, Thangaraju M, Hatanaka T, Itagaki S, Munn DH, Prasad PD, Ganapathy V. Interaction of tryptophan derivatives with SLC6A14 (ATB(0,+)) reveals the potential of the transporter as a drug target for cancer chemotherapy. Biochem J. 2008 Sep 15;414(3):343-55.

Xu H, Oriss TB, Fei M, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, Ray A. Indoleamine 2,3-dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation. Proc Natl Acad Sci USA. 2008 May 6;105(18):6690-5.

Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Taylor PA, Mellor AL, Munn DH, Blazar BR. Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality. Blood. 2008 Mar 15;111(6):3257-65.

Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol. 2008 Jan;8(1):74-80. Review. Erratum in: Nat Rev Immunol. 2008 Feb;8(2):160.

Banerjee T, DuHadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ. A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3 dioxygenase.Oncogene. 2008 May 1;27(20):2851-7.

Publications are updated quarterly. For a complete listing, see Dr. Munn’s work on PubMed.

* denotes corresponding author

 

Affiliations

  • Professor, Pediatrics, Pathology, Cellular Biology and Anatomy, and College of Graduate Studies, Medical College of Georgia, Georgia Regents University
  • Associate Professor, Medicine, Medical College of Georgia
  • Member, The GRU MCG Immunotherapy Center
  • Member, Society for Pediatric Research