David Munn, MD
Professor, Pediatric Oncology
Co-Director, Pediatric Immunotherapy Program
Our research is focused on activating the body’s own immune system to fight cancer. We work on discovering the ways in which cancers suppress the immune system, and on identifying the molecular mechanisms that tumors use to escape from immune attack. Along with our collaborators, we have developed new drugs and clinical strategies to activate the immune response against tumors and enlist the patients’ own immune system to enhance the effectiveness of conventional chemotherapy drugs and radiation. Target diseases include adult and pediatric solid tumors and leukemia’s. Dr. Munn’s research is funded by the National Institutes of Health and support from charitable foundation donors.
The David Munn Lab
Health Sciences Campus
Georgia Cancer Center - M. Bert Storey Research Building
1410 Laney Walker Blvd., CN-4141, Augusta, GA 30912
Our research is focused on tumor immunology and the molecular mechanisms of immune suppression and tolerance in the tumor microenvironment. The laboratory studies the regulation of anti-tumor T cell activation by tolerogenic dendritic cells and regulatory T cells (Tregs) in the setting of cancer.
Major focus areas in the laboratory include (i) activation of suppressive tumor-associated Tregs via the PTEN lipid-phosphatase pathway; (ii) regulation of the dendritic cell (DC) population in tumors and the choice between tolerogenic vs. immunogenic DCs; and (iii) tolerance-induction to dying tumor cells mediated via the enzyme indoleamine 2,3-dioxygenase (IDO) and PTEN+ Tregs. Active projects include:
Basic-science studies of the role of the PTEN-phosphatase pathway in Tregs, including the regulation of the suppressor phenotype vs. destabilization and reprogramming during inflammation. The translational goal of these studies is to develop orally-bioavailable small-molecule inhibitors drugs to block this novel immune-checkpoint and destabilize Tregs in tumors.
Molecular mechanisms of inflammation-induced differentiation of immunogenic dendritic cells, and the suppression of immunogenic DCs by PTEN+ Tregs. The translational goal of these studies is to develop orally-bioavailable small-molecule drugs that induce differentiation of immunogenic DCs in tumors.
Basic and pre-clinical studies of immune response to dying tumor cells after chemotherapy; and synergy between conventional chemotherapy and novel forms of immunotherapy targeting Tregs and DCs.
Design and immune-monitoring of Phase I and Phase II clinical trials of IDO-inhibitor drugs in combination with chemotherapy, radiation and checkpoint blockade. These include trials in both adult patients and first-in-children pediatric trials, in conjunction with the Pediatric Immunotherapy Service and Dr. Theodore Johnson.
Sharma MD, Shinde R, McGaha TL, Huang L, Holmgaard RB, Wolchok JD, Mautino MR, Celis E, Sharpe AH, Francisco LM, Powell JD, Yagita H, Mellor AL, Blazar BR, Munn DH*. The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment. Science Advances 1, e1500845 (Nov., 2015)
Sharma MD, Rodriguez PC, Koehn BH, Baban B, Cui Y, Guo G, Shimoda M, Pacholczyk R, Shi H, Lee EJ, Xu H, Johnson TS, He Y, Mergoub T, Venable C, Bronte V, Wolchok JD, Blazar BR, Munn DH*. Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c(+)CD103(+) Monocytic Antigen-Presenting Cells in Tumors. Immunity. 48:91-106 (Jan., 2018)
Shinde R, Hezaveh K, Halaby MJ, Kloetgen A, Chakravarthy A, Medina TDS, Deol R, Manion KP, Baglaenko Y, Eldh M, Lamorte S, Wallace D, Chodisetti S, Ravishankar B, Liu H, Chaudhary K, Munn DH, Tsirigos A, Madaio M, Gabrielsson S, Touma Z, Wither J, Carvalho DD, McGaha TL. Apoptotic cell induced TLR9-dependent AhR activity is required for immunologic tolerance and suppression of lupus. Nature Immunol. 19:571-582 (May, 2018)
Cao Y, Trillo-Tinoco J, Sierra RA, Anadon C, Dai W, Mohamed E, Cen L, Costich TL, Magliocco A, Marchion D, Klar R, Michel S, Jaschinski F, Reich RR, Mehrotra S, Cubillos-Ruiz JR, Munn DH, Conejo-Garcia JR, Rodriguez PC. ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression. Nat Commun. 10(1):1280 (Mar., 2019)
Halaby MJ, Hezaveh K, Lamorte S, Ciudad MT, Kloetgen A, MacLeod BL, Guo M, Chakravarthy A, Medina TDS, Ugel S, Tsirigos A, Bronte V, Munn DH, Pugh TJ, De Carvalho DD, Butler MO, Ohashi PS, Brooks DG, McGaha TL. GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment. Science Immunol. 4(42):eaax8189 (Dec., 2019)
Mohamed E, Sierra RA, Trillo-Tinoco J, Cao Y, Innamarato P, Payne KK, deMingo-Pulido A, Mandula J, Zhang S, Thevenot P, Biswas S, Abdalla SK, Costich TL, Hänggi K, Anadon CM, Flores ER, Haura E, Mehrotra S, Pilon-Thomas S, Ruffell B, Munn DH, Cubillos-Ruiz JR, Conejo-Garcia JR, Rodriguez PC. ER stress sensor PERK governs myeloid cell-driven immunosuppression in tumors through NRF2-dependent inhibition of STING signaling. Immunity. 52:668–682 (April, 2020)
Ding ZC, Shi H, Aboelella NS, Fesenkova K, Park EJ, Liu Z, Pei L, Li J, McIndoe RA, Xu H, Piazza GA, Blazar BR, Munn DH, Zhou G. Persistent STAT5 activation reprograms the epigenetic landscape in CD4(+) T cells to drive polyfunctionality and antitumor immunity. Science Immunol. 5:eaba5962 (Oct., 2020)
Anita Sharma, PhD
Zuzana Berrong, PhD