Photo of Michael Dougan,  MD, PhD

Michael Dougan, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-6122

Michael Dougan, MD, PhD

Massachusetts General Hospital


  • Assistant Professor, Medicine, Harvard Medical School
  • Assistant in Medicine, Medicine, Division of Gastroenterology, Massachusetts General Hospital


Research Abstract

I have a longstanding interest in interaction between the immune system and cancer. As a dissertation student with Dr. Glenn Dranoff’s lab at Dana-Farber Cancer Institute, I established the first model of lung cancer caused by a defect in immune regulation. In this model, deficiencies in the cytokines GM-CSF, IL-3 and IFN-γ, lead to a combination of tumor promoting inflammation and defective antitumor immunity that produces highly penetrant pulmonary adenocarcinomas. This work provided early pre-clinical data supporting a dual role for the immune response in lung cancer, with failure of adaptive immunity combining with innate inflammation to drive lung cancer development. These findings were subsequently validated in clinical trials of checkpoint blockade which confirmed a role for adaptive immunity in controlling lung cancer, and in the CANTOS trial which demonstrated reduced lung cancer incidents in patients treated with antibodies that block the innate inflammatory cytokine IL-1β.

My dissertation work also identified a novel regulatory role for the Inhibitor of Apoptosis (IAP) family of proteins in T cell activation through NF-B signaling downstream of TNF family costimulatory receptors. I used pharmacologic IAP inhibitors to study the therapeutic implications of this finding, combining IAP antagonists with a tumor vaccine to augment antitumor responses. This finding was the basis for subsequent work that has exploited the immune modulating properties of IAP antagonists to treat multiple myeloma and glioblastoma in preclinical models, and is now being investigated in multiple clinical trials.

As a resident and Gastroenterology fellow at Massachusetts General Hospital (MGH), I joined Dr. Hidde Ploegh’s lab at the Whitehead Institute for Biomedical Research, where I generated and characterized single domain antibodies (VHHs) to several immune receptors. I used these VHHs for multiple pre-clinical applications. By fusing VHHs to cytokines, I developed a panel of modified cytokines with novel binding properties and improved therapeutic effects in a variety of mouse models. I showed that VHHs against CD47 can enhance responses to murine melanoma in combination with immune modulating antibodies, and in my own lab, have established a syngeneic model for evaluating the toxicities of CD47 targeted therapeutics. By tagging these VHH to radioisotopes, I worked with two other postdoctoral fellows to comprehensively image PD-L1 in a live mouse, and to track CD8 T cells responses in mice undergoing immunotherapy using immuno-positron emission tomography (PET). PD-L1 PET unexpectedly showed that PD-L1 is primarily expression by brown adipose tissue (BAT), and is an activation-independent marker for brown adipocytes, a finding with implications that I continue to explore in my own lab.

As an independent investigator, I have focused my efforts on understanding the etiology and immune mechanisms underlying the immune-related adverse events (irAEs) resulting from cancer immunotherapy, a window into the endogenous function of the immune receptors targeted by these therapies. My research dovetails with my clinical work, where I specialize in treating gastrointestinal (GI) irAEs resulting from “checkpoint” receptor blockade, which are often treatment limiting. Management relies on systemic corticosteroids, which are likely to have deleterious effects on antitumor responses. My goal is to use a detailed mechanistic understanding of gastrointestinal irAEs to develop novel treatment strategies that do not interfere with antitumor immunity, as well as to understand on a more fundamental level, how individual immune receptors regulate immune homeostasis in the GI tract.


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  • Pisuchpen N, Durbin SM, Mooradian MJ, Fintelmann FJ, Reynolds KL, Dougan M, Kambadakone A. Multi-detector computed tomography (MDCT)-based severity score as a prognostic tool in patients with suspected immune checkpoint inhibitor therapy associated colitis. Eur Radiol 2021. PubMed
  • Roehle K, Qiang L, Ventre KS, Heid D, Ali LR, Lenehan P, Heckler M, Crowley SJ, Stump CT, Ro G, Godicelj A, Bhuiyan AM, Yang A, Quiles Del Rey M, Biary T, Luoma AM, Bruck PT, Tegethoff JF, Nopper SL, Li J, Byrne KT, Pelletier M, Wucherpfennig KW, Stanger BZ, Akin JJ, Mancias JD, Agudo J, Dougan M, Dougan SK. cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes. Sci Transl Med 2021. PubMed
  • Heckler M, Ali LR, Clancy-Thompson E, Qiang L, Ventre KS, Lenehan P, Roehle K, Luoma A, Boelaars K, Peters V, McCreary J, Boschert T, Wang ES, Suo S, Marangoni F, Mempel TR, Long HW, Wucherpfennig KW, Dougan M, Gray NS, Yuan GC, Goel S, Tolaney SM, Dougan SK. Inhibition of CDK4/6 promotes CD8 T-cell memory formation. 2021. PubMed
  • Dougan M, Luoma AM, Dougan SK, Wucherpfennig KW. Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell 2021; 184:1575-1588. PubMed
  • Walsh MJ, Dougan M. Checkpoint blockade toxicities: Insights into autoimmunity and treatment. Semin Immunol 2021. PubMed
  • Molina GE, Zubiri L, Cohen JV, Durbin SM, Petrillo L, Allen IM, Murciano-Goroff YR, Dougan M, Thomas MF, Faje AT, Rengarajan M, Guidon AC, Chen ST, Okin D, Medoff BD, Nasrallah M, Kohler MJ, Schoenfeld SR, Karp Leaf RS, Sise ME, Neilan TG, Zlotoff DA, Farmer JR, Mooradian MJ, Bardia A, Mai M, Sullivan RJ, Semenov YR, Villani AC, Reynolds KL. Temporal Trends and Outcomes Among Patients Admitted for Immune-Related Adverse Events: A Single-Center Retrospective Cohort Study from 2011 to 2018. Oncologist 2021. PubMed
  • Thompson LL, Katznelson E, Leet DE, Durbin SM, Yoon J, Reynolds KL, Dougan ML, Chen ST. Impact of systemic corticosteroids on survival outcomes in immune checkpoint inhibitor-induced gastroenterocolitis. Eur J Cancer 2020; 142:143-146. PubMed
  • Dougan M, Wang Y, Rubio-Tapia A, Lim JK. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review. Gastroenterology 2021. PubMed
  • Cohen JV, Dougan M, Zubiri L, Reynolds KL, Sullivan RJ, Misdraji J. Liver biopsy findings in patients on immune checkpoint inhibitors. Mod Pathol 2020. PubMed
  • Shannon VR, Anderson R, Blidner A, Choi J, Cooksley T, Dougan M, Glezerman I, Ginex P, Girotra M, Gupta D, Johnson DB, Suarez-Almazor ME, Rapoport BL. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events: pulmonary toxicity. Support Care Cancer 2020. PubMed
  • Blidner AG, Choi J, Cooksley T, Dougan M, Glezerman I, Ginex P, Girotra M, Gupta D, Johnson D, Shannon VR, Suarez-Almazor M, Rapoport BL, Anderson R. Cancer immunotherapy-related adverse events: causes and challenges. Support Care Cancer 2020. PubMed
  • Suarez-Almazor ME, Pundole X, Abdel-Wahab N, Johnson DB, Gupta D, Glezerman I, Cooksley T, Anderson R, Blidner A, Choi J, Dougan M, Ginex P, Girotra M, Shannon VR, Rapoport BL. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-mediated cardiovascular, rheumatic, and renal toxicities from checkpoint inhibitors. Support Care Cancer 2020. PubMed
  • Choi J, Anderson R, Blidner A, Cooksley T, Dougan M, Glezerman I, Ginex P, Girotra M, Gupta D, Johnson D, Shannon VR, Suarez-Almazor M, Rapoport BL, Lacouture ME. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe dermatological toxicities from checkpoint inhibitors. Support Care Cancer 2020. PubMed
  • Dougan M, Blidner AG, Choi J, Cooksley T, Glezerman I, Ginex P, Girotra M, Gupta D, Johnson D, Shannon VR, Suarez-Almazor M, Anderson R, Rapoport BL. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors. Support Care Cancer 2020. PubMed
  • Cooksley T, Girotra M, Ginex P, Gordon RA, Anderson R, Blidner A, Choi J, Dougan M, Glezerman I, Gupta D, Johnson D, Shannon VR, Suarez-Almazor M, Rapoport BL. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune checkpoint inhibitor endocrinopathies and the role of advanced practice providers in the management of immune-mediated toxic Support Care Cancer 2020. PubMed
  • Luoma AM, Suo S, Williams HL, Sharova T, Sullivan K, Manos M, Bowling P, Hodi FS, Rahma O, Sullivan RJ, Boland GM, Nowak JA, Dougan SK, Dougan M, Yuan GC, Wucherpfennig KW. Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy. Cell 2020. PubMed
  • Grover S, Dougan M, Tyan K, Giobbie-Hurder A, Blum SM, Ishizuka J, Qazi T, Elias R, Vora KB, Ruan AB, Martin-Doyle W, Manos M, Eastman L, Davis M, Gargano M, Haq R, Buchbinder EI, Sullivan RJ, Ott PA, Hodi FS, Rahma OE. Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis. Cancer 2020. PubMed
  • Badran Y, Shih A, Leet D, Mooradian MJ, Coromilas A, Chen J, Kem M, Zheng H, Borowsky J, Misdraji J, Mino-Kenudson M, Dougan M. Immune checkpoint inhibitor-associated celiac disease. J Immunother Cancer 2020. PubMed
  • Mooradian MJ, Wang DY, Coromilas A, Lumish M, Chen T, Giobbie-Hurder A, Johnson DB, Sullivan RJ, Dougan M. Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis. J Immunother Cancer 2020. PubMed
  • Xie YJ, Dougan M, Ingram JR, Pishesha N, Fang T, Momin N, Ploegh HL. Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments. Cancer Immunol Res 2020; 8:518-529. PubMed
  • Dougan M. Gastrointestinal and Hepatic Complications of Immunotherapy: Current Management and Future Perspectives. Curr Gastroenterol Rep 2020; 22:15. PubMed
  • Zubiri L, Allen IM, Taylor MS, Guidon AC, Chen ST, Schoenfeld SR, Neilan TG, Sise ME, Mooradian MJ, Rubin KM, Leaf RK, Parikh AR, Faje A, Gainor JF, Cohen JV, Fintelmann FJ, Kohler MJ, Dougan M, Reynolds KL. Immune-Related Adverse Events in the Setting of PD-1/L1 Inhibitor Combination Therapy. Oncologist 2020; 25:e398-e404. PubMed
  • Crowley SJ, Bruck PT, Bhuiyan MA, Mitchell-Gears A, Walsh MJ, Zhangxu K, Ali LR, Jeong HJ, Ingram JR, Knipe DM, Ploegh HL, Dougan M, Dougan SK. Neoleukin-2 enhances anti-tumour immunity downstream of peptide vaccination targeted by an anti-MHC class II VHH. Open Biol 2020; 10:190235. PubMed
  • Dougan M, Pietropaolo M. Time to dissect the autoimmune etiology of cancer antibody immunotherapy. J Clin Invest 2020; 130:51-61. PubMed
  • Dougan M. Understanding and Overcoming the Inflammatory Toxicities of Immunotherapy. Cancer Immunol Res 2021; 8:1230-1235. PubMed
  • Fernandes RA, Su L, Nishiga Y, Ren J, Bhuiyan AM, Cheng N, Kuo CJ, Picton LK, Ohtsuki S, Majzner RG, Rietberg SP, Mackall CL, Yin Q, Ali LR, Yang X, Savvides CS, Sage J, Dougan M, Garcia KC. Immune receptor inhibition through enforced phosphatase recruitment. Nature 2021; 586:779-784. PubMed
  • Durbin SM, Mooradian MJ, Fintelmann FJ, Zubiri L, Chute DF, Kambadakone A, Pisuchpen N, Reynolds KL, Dougan M. Diagnostic utility of CT for suspected immune checkpoint inhibitor enterocolitis. J Immunother Cancer 2021. PubMed
  • Abu-Sbeih H, Faleck DM, Ricciuti B, Mendelsohn RB, Naqash AR, Cohen JV, Sellers MC, Balaji A, Ben-Betzalel G, Hajir I, Zhang J, Awad MM, Leonardi GC, Johnson DB, Pinato DJ, Owen DH, Weiss SA, Lamberti G, Lythgoe MP, Manuzzi L, Arnold C, Qiao W, Naidoo J, Markel G, Powell N, Yeung SJ, Sharon E, Dougan M, Wang Y. Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease. J Clin Oncol 2019. PubMed
  • Zubiri L, Allen IM, Taylor MS, Guidon AC, Chen ST, Schoenfeld SR, Neilan TG, Sise ME, Mooradian MJ, Rubin KM, Leaf RK, Parikh AR, Faje A, Gainor JF, Cohen JV, Fintelmann FJ, Kohler MJ, Dougan M, Reynolds KL. Immune-Related Adverse Events in the Setting of PD-1/L1 Inhibitor Combination Therapy. Oncologist 2019. PubMed
  • Hughes MS, Molina GE, Chen ST, Zheng H, Deshpande V, Fadden R, Sullivan RJ, Dougan M. Budesonide treatment for microscopic colitis from immune checkpoint inhibitors. J Immunother Cancer 2019; 7:292. PubMed
  • Schoenfeld SR, Aronow ME, Leaf RK, Dougan M, Reynolds KL. Diagnosis and Management of Rare Immune-Related Adverse Events. Oncologist 2019. PubMed
  • Hughes MS, Zheng H, Zubiri L, Molina GE, Chen ST, Mooradian MJ, Allen IM, Reynolds KL, Dougan M. Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control. Cancer Med 2019; 8:4986-4999. PubMed
  • Dougan SK, Dougan M. SMAC mimetics throw a molecular switch to control T17 responses. Sci Signal 2019. PubMed
  • Zhang ML, Neyaz A, Patil D, Chen J, Dougan M, Deshpande V. Immune-Related Adverse Events in the Gastrointestinal Tract: Diagnostic Utility of Upper Gastrointestinal Biopsies. Histopathology 2019. PubMed
  • Molina GE, Allen IM, Hughes MS, Zubiri L, Lee H, Mooradian MJ, Reynolds KL, Dougan M, Chen ST. Prognostic Implications of Co-Occurring Dermatologic and Gastrointestinal Toxicity from Immune Checkpoint Inhibition Therapy for Advanced Malignancies: A Retrospective Cohort Study. J Am Acad Dermatol 2019. PubMed
  • Dougan M, Dougan SK. Programmable bacteria as cancer therapy. Nat Med 2019. PubMed
  • Pauken KE, Dougan M, Rose NR, Lichtman AH, Sharpe AH. Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities. Trends Immunol 2019; 40:511-523. PubMed
  • Dougan M, Dranoff G, Dougan SK. GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation. Immunity 2019; 50:796-811. PubMed
  • Xie YJ, Dougan M, Jailkhani N, Ingram J, Fang T, Kummer L, Momin N, Pishesha N, Rickelt S, Hynes RO, Ploegh H. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proc Natl Acad Sci U S A 2019. PubMed
  • Bello E, Cohen JV, Mino-Kenudson M, Dougan M. Antitumor response to microscopic melanoma in the gastric mucosa mimicking ipilimumab-induced gastritis. J Immunother Cancer 2019; 7:41. PubMed
  • Silva DA, Yu S, Ulge UY, Spangler JB, Jude KM, Labão-Almeida C, Ali LR, Quijano-Rubio A, Ruterbusch M, Leung I, Biary T, Crowley SJ, Marcos E, Walkey CD, Weitzner BD, Pardo-Avila F, Castellanos J, Carter L, Stewart L, Riddell SR, Pepper M, Bernardes GJL, Dougan M, Garcia KC, Baker D. De novo design of potent and selective mimics of IL-2 and IL-15. Nature 2019; 565:186-191. PubMed
  • Reynolds K, Thomas M, Dougan M. Diagnosis and Management of Hepatitis in Patients on Checkpoint Blockade. Oncologist 2018; 23:991-997. PubMed
  • Dougan SK, Dougan M. Regulation of innate and adaptive antitumor immunity by IAP antagonists. 2018. PubMed
  • Krall JA, Reinhardt F, Mercury OA, Pattabiraman DR, Brooks MW, Dougan M, Lambert AW, Bierie B, Ploegh HL, Dougan SK, Weinberg RA. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci Transl Med 2018. PubMed
  • Dougan M, Ingram JR, Jeong HJ, Mosaheb MM, Bruck PT, Ali L, Pishesha N, Blomberg O, Tyler PM, Servos MM, Rashidian M, Nguyen QD, von Andrian UH, Ploegh HL, Dougan SK. Targeting Cytokine Therapy to the Pancreatic Tumor Microenvironment Using PD-L1-Specific VHHs. Cancer Immunol Res 2018; 6:389-401. PubMed
  • Ingram JR, Blomberg OS, Rashidian M, Ali L, Garforth S, Fedorov E, Fedorov AA, Bonanno JB, Le Gall C, Crowley S, Espinosa C, Biary T, Keliher EJ, Weissleder R, Almo SC, Dougan SK, Ploegh HL, Dougan M. Anti-CTLA-4 therapy requires an Fc domain for efficacy. Proc Natl Acad Sci U S A 2018. PubMed
  • Clancy-Thompson E, Ali L, Bruck PT, Exley MA, Blumberg RS, Dranoff G, Dougan M, Dougan SK. IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells. Cancer Immunol Res 2018; 6:25-35. PubMed
  • Ingram JR, Dougan M, Rashidian M, Knoll M, Keliher EJ, Garrett S, Garforth S, Blomberg OS, Espinosa C, Bhan A, Almo SC, Weissleder R, Lodish H, Dougan SK, Ploegh HL. PD-L1 is an activation-independent marker of brown adipocytes. Nat Commun 2017; 8:647. PubMed
  • Ingram JR, Blomberg OS, Sockolosky JT, Ali L, Schmidt FI, Pishesha N, Espinosa C, Dougan SK, Garcia KC, Ploegh HL, Dougan M. Localized CD47 blockade enhances immunotherapy for murine melanoma. Proc Natl Acad Sci U S A 2017; 114:10184-10189. PubMed
  • Rashidian M, Ingram JR, Dougan M, Dongre A, Whang KA, LeGall C, Cragnolini JJ, Bierie B, Gostissa M, Gorman J, Grotenbreg GM, Bhan A, Weinberg RA, Ploegh HL. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med 2018; 214:2243-2255. PubMed
  • Dougan M, Dougan SK. Targeting Immunotherapy to the Tumor Microenvironment. J Cell Biochem 2017. PubMed
  • Tyler PM, Servos MM, de Vries RC, Klebanov B, Kashyap T, Sacham S, Landesman Y, Dougan M, Dougan SK. Clinical dosing regimen of selinexor maintains normal immune homeostasis and T cell effector function in mice: implications for combination with immunotherapy. Mol Cancer Ther 2017. PubMed
  • Dougan M. Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract. 2017; 8:1547. PubMed
  • Sockolosky JT, Dougan M, Ingram JR, Ho CC, Kauke MJ, Almo SC, Ploegh HL, Garcia KC. Durable antitumor responses to CD47 blockade require adaptive immune stimulation. Proc Natl Acad Sci U S A 2018; 113:E2646-54. PubMed
  • Tafesse FG, Rashidfarrokhi A, Schmidt FI, Freinkman E, Dougan S, Dougan M, Esteban A, Maruyama T, Strijbis K, Ploegh HL. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans. PLoS Pathog. 2017; 11:e1005188. PubMed
  • Rashidian M, Keliher E, Dougan M, Juras PK, Cavallari M, Wojtkiewicz GR, Jacobsen J, Edens JG, Tas JM, Victora G, Weissleder R, Ploegh H. The use of F-2-fluorodeoxyglucose (FDG) to label antibody fragments for immuno-PET of pancreatic cancer. ACS Cent Sci 2017; 1:142-147. PubMed
  • Dougan SK, Dougan M, Kim J, Turner JA, Ogata S, Cho HI, Jaenisch R, Celis E, Ploegh HL. Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show equivalent antitumor activity. Cancer Immunol Res 2014; 1:99-111. PubMed
  • Dougan M, Li D, Neuberg D, Mihm M, Googe P, Wong KK, Dranoff G. A dual role for the immune response in a mouse model of inflammation-associated lung cancer. J Clin Invest 2011; 121:2436-46. PubMed
  • Dougan M, Dougan S, Slisz J, Firestone B, Vanneman M, Draganov D, Goyal G, Li W, Neuberg D, Blumberg R, Hacohen N, Porter D, Zawel L, Dranoff G. IAP inhibitors enhance co-stimulation to promote tumor immunity. J Exp Med 2010; 207:2195-206. PubMed
  • Dougan M,Dranoff G. The immune response to tumors. Curr Protoc Immunol 2009; Chapter 20:Unit 20.11. PubMed
  • Dougan M,Dranoff G. Immune therapy for cancer. Annu Rev Immunol 2008; 27:83-117. PubMed
  • Dougan M, Dranoff G. Inciting inflammation: the RAGE about tumor promotion. J Exp Med 2008; 205:267-70. PubMed
  • Enzler T, Gillessen S, Dougan M, Allison JP, Neuberg D, Oble DA, Mihm M, Dranoff G. Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of beta cells. Blood 2007; 110:954-61. PubMed
  • Jinushi M, Nakazaki Y, Dougan M, Carrasco DR, Mihm M, Dranoff G. MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF. J Clin Invest 2007; 117:1902-13. PubMed