Headerlogotextwithshieldsshadowed
Dan Duda
Director of Translational Research in GI Radiation Oncology
Duda Lab

Duda Lab Research

Duda_HMS_CV.pdf

Education and Academic Appointments

Dr. Duda obtained a DMD from the University of Medicine Iasi, Romania, in 1993, and then earned a Ph.D. in Medical Sciences (Gastrointestinal Surgery) from Tohoku University Graduate School of Medicine, Sendai, Japan, in 2001. After graduation, he pursued postdoctoral training with Professor Rakesh K. Jain in the Steele Laboratories for Tumor Biology, Department of Radiation Oncology, MGH, and Harvard Medical School in Boston. Dr. Duda became a Junior Faculty member at Harvard (Instructor) in 2004. He then rose to Full Investigator at MGH Research Institute in 2016 and Associate Professor of Tumor Biology (Radiation Oncology) in 2012. In 2016, Dr. Duda was appointed Director of Translational Research in Gastrointestinal Radiation Oncology at MGH. In 2021, he received the honorary degree "Doctor Honoris Causa" from the University of Medicine Iasi, Romania, his Alma Mater.

Research Goals of the Duda Lab

Over the last decade and a half, Dr. Duda has built a productive Liver Cancer Research Program at Steele Laboratories for Tumor Biology. The translational goal of this program is to increase the durability of response to the most effective available therapies. The approach is to identify new cellular and molecular mechanisms of local and metastatic tumor progression and treatment resistance and validate them as new targets for combination therapies for these cancers.

His group studies the activity of agents targeting the tumor microenvironment (antiangiogenic or antifibrotic agents) or targeting the cancer cells (radiotherapy, chemotherapy, targeted agents) in combination with immunotherapy approaches. To this end, they developed preclinical models that reproduce hallmarks of human cancers (i.e., genetically engineered models of primary hepatocellular carcinoma and cholangiocarcinoma, and metastatic pancreatic, breast, and prostate carcinomas). In parallel, they are conducting correlative studies of biomarkers of response to the same approaches in clinical trials in cancer patients. Dr. Duda's research is supported by multiple R01 grants from the National Cancer Institute (NCI), Department of Defense (DoD) awards, and agreements with Industry partners.

Track Record and Service

Dr. Duda has authored over 250 publications so far. Of these, 160+ are original reports, including basic research published in Nature, Nature Medicine, Nature Biotechnology, Nature Genetics, Nature Communications, Cell, Cancer Cell, Science Translational Medicine, JNCI, Gut, and Hepatology, and clinical reports published in Journal of Clinical Oncology, npj Precision Oncology, and JAMA Oncology. Over the last two decades, he has been invited to present our results at over 200 local, national and international meetings, including in Grand Rounds (Harvard, Mayo Clinic, Yale, Fred Hutchinson Cancer Center), Plenary and State-of-the-art Talks (AACR, ISSCR, IASGO, IAP), and several Keynote Lectures. Dr. Duda has received multiple awards for his research, including from the AACR, Cancer Research Institute (CRI), IASGO, and MGH. He became an Honorary Member of the Academy of Medical Sciences of Romania in 2012; was inducted into the College of Fellows of the American Institute for Medical and Biomedical Engineering (AIMBE) in 2020; and was elected as a 2021 American Association for the Advancement of Science (AAAS) Fellow in 2022.

Dr. Duda has been a chartered or ad-hoc Member and Chair or co-Chair of US NCI, American Cancer Society (ACS), US Department of Defense (DOD), and Belgium FWO Med4 panels since 2012. He is a  Founding Editor of Surgery, Gastroenterology and Oncology, a Senior Associate Editor of the International Journal of Radiation Oncology*Biology*Physics, and an Editorial Board member for several other journals, including Clinical & Translational Radiation Oncology, Journal of Hepatocellular Carcinoma, Digestive Surgery, and Cancers. Since 2015, he has been serving as the Secretary-General of the IASGO. In addition, Dr. Duda is a member of the American Association for the Study of Liver Diseases (AASLD) Liver Fibrosis Special Interest Group; a member of the NCI Hepatobiliary Task Force for Immuno-Oncology Biomarkers; and a member of the SWOG Cancer Research Network, GI and Translational Medicine GI Committees. In 2023, Dr. Duda will chair the Forbeck Forum on “The Biology and Treatment of Hepatocellular Carcinoma”. 

Teaching

Dr. Duda teaches tumor biology and translational oncology through the daily supervision of postdoctoral research fellows and graduate and undergraduate students (50+ in the last 15 years). As a passionate supporter of IASGO's mission to globalize the best medical practice and knowledge worldwide, he has been coordinating, teaching, and directing Postgraduate Courses in 29 countries in Asia, Europe, Africa, and the Americas since 2013. He has taught nationally in ASTRO and RTOG translational meetings for residents and clinicians and locally in the MIT-HMS HST Program since 2005. In addition, he has been coordinating a research exchange student program with the University of Muenster, Germany, since 2015 and directing the Annual Course titled "Methods in Biomedical Engineering, Tumor Biology and Immunology" at MGH, since 2004. He authored the "IASGO Textbook of Multi-Disciplinary Management of Hepato-Pancreato-Biliary Diseases", published in 2022.

(For more information, see full CV above.) 

Lab News

Sequencing of drug combinations could amplify the anti-tumor immune response in liver cancer

A new therapeutic strategy for hepatocellular cancer (HCC) that initially primes the tumor with an immune checkpoint inhibitor before using a multikinase inhibitor drug showed great promise for treating patients with the deadly disease, a Massachusetts General Hospital (MGH) study found. In a paper published in Journal of the National Cancer Institute, researchers reported that the new sequencing approach enhanced the effectiveness of the dual drug therapy, potentially allowing de-escalation of the prolonged use of medications and thus reducing toxic drug exposure...

Steele researchers restore function in a gene that can suppress liver cancer and enhance immunotherapy

A team of researchers from Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) has reprogrammed the tumor microenvironment of liver cancer by using mRNA nanoparticles. This technology, similar to the one used in COVID-19 vaccines, restored the function of the p53 master regulator gene, a tumor suppressor mutated in not just liver but also other types of cancer. When used in combination with immune checkpoint blockade (ICB), the p53 mRNA nanoparticle approach not only induced suppression of tumor growth but also significantly increased antitumor immune responses in hepatocellular carcinoma (HCC) laboratory models. The results of the study were published in Nature Communications.

read more here

Dan Duda Elected 2021 AAAS Fellow
Improving treatment of liver cancer

Steele researchers discover a promising approach to inhibiting a less frequent but highly treatment-refractory liver cancer

Press release

Article URL

New strategy for immunotherapy of liver cancer

Judiciously dosed regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma (HCC). 

Article URL


Selected Publications (from total of 214)

Kikuchi H, Matsui A, Morita S, Amoozgar Z, Inoue K, Ruan Z, Staiculescu D, Wong JS, Huang P, Yau T, Jain RK, Duda DG

Increased CD8+ T-Cell Infiltration and Efficacy for Multikinase Inhibitors after PD-1 Blockade in Hepatocellular Carcinoma.

J Natl Cancer Inst. 2022;114(9):1301-1305 - PMID: 35288743 - PMCID: PMC9468280 - DOI: 10.1093/jnci/djac051
Xiao Y, Chen J, Zhou H, Zeng X, Ruan Z, Pu Z, Jiang X, Matsui A, Zhu L, Amoozgar Z, Chen DS, Han X, Duda DG, Shi J

Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy.

Nat Commun. 2022;13(1):758 - PMID: 35140208 - PMCID: PMC8828745 - DOI: 10.1038/s41467-022-28279-8
Aoki S, Inoue K, Klein S, Halvorsen S, Chen J, Matsui A, Nikmaneshi MR, Kitahara S, Hato T, Chen X, Kawakubo K, Nia HT, Chen I, Schanne DH, Mamessier E, Shigeta K, Kikuchi H, Ramjiawan RR, Schmidt TC, Iwasaki M, Yau T, Hong TS, Quaas A, Plum PS, Dima S, Popescu I, Bardeesy N, Munn LL, Borad MJ, Sassi S, Jain RK, Zhu AX, Duda DG

Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma.

Gut. 2021;71(1):185-193 - PMID: 33431577 - PMCID: PMC8666816 - DOI: 10.1136/gutjnl-2020-322493
Pfister D, Núñez NG, Pinyol R, Govaere O, Pinter M, Szydlowska M, Gupta R, Qiu M, Deczkowska A, Weiner A, Müller F, Sinha A, Friebel E, Engleitner T, Lenggenhager D, Moncsek A, Heide D, Stirm K, Kosla J, Kotsiliti E, Leone V, Dudek M, Yousuf S, Inverso D, Singh I, Teijeiro A, Castet F, Montironi C, Haber PK, Tiniakos D, Bedossa P, Cockell S, Younes R, Vacca M, Marra F, Schattenberg JM, Allison M, Bugianesi E, Ratziu V, Pressiani T, D'Alessio A, Personeni N, Rimassa L, Daly AK, Scheiner B, Pomej K, Kirstein MM, Vogel A, Peck-Radosavljevic M, Hucke F, Finkelmeier F, Waidmann O, Trojan J, Schulze K, Wege H, Koch S, Weinmann A, Bueter M, Rössler F, Siebenhüner A, Dosso S, Mallm JP, Umansky V, Jugold M, Luedde T, Schietinger A, Schirmacher P, Emu B, Augustin HG, Billeter A, Müller-Stich B, Kikuchi H, Duda DG, Kütting F, Waldschmidt DT, Ebert MP, Rahbari N, Mei HE, Schulz AR, Ringelhan M, Malek N, Spahn S, Bitzer M, Ruiz de Galarreta M, Lujambio A, Dufour JF, Marron TU, Kaseb A, Kudo M, Huang YH, Djouder N, Wolter K, Zender L, Marche PN, Decaens T, Pinato DJ, Rad R, Mertens JC, Weber A, Unger K, Meissner F, Roth S, Jilkova ZM, Claassen M, Anstee QM, Amit I, Knolle P, Becher B, Llovet JM, Heikenwalder M

NASH limits anti-tumour surveillance in immunotherapy-treated HCC.

Nature. 2021;592(7854):450-456 - PMID: 33762733 - PMCID: PMC8046670 - DOI: 10.1038/s41586-021-03362-0
Shigeta K, Matsui A, Kikuchi H, Klein S, Mamessier E, Chen IX, Aoki S, Kitahara S, Inoue K, Shigeta A, Hato T, Ramjiawan RR, Staiculescu D, Zopf D, Fiebig L, Hobbs GS, Quaas A, Dima S, Popescu I, Huang P, Munn LL, Cobbold M, Goyal L, Zhu AX, Jain RK, Duda DG

Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma.

J Immunother Cancer. 2020;8(2):ePub - PMID: 33234602 - PMCID: PMC7689089 - DOI: 10.1136/jitc-2020-001435
Goyal L, Sirard C, Schrag M, Kagey MH, Eads JR, Stein S, El-Khoueiry AB, Manji GA, Abrams TA, Khorana AA, Miksad R, Mahalingam D, Zhu AX, Duda DG

Phase 1 and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer.

Clin Cancer Res. 2020;26(23):6158-6167 - PMID: 32878766 - DOI: 10.1158/1078-0432.CCR-20-1310
Millar DG, Ramjiawan RR, Kawaguchi K, Gupta N, Chen J, Zhang S, Nojiri T, Ho WW, Aoki S, Jung K, Chen I, Shi F, Heather JM, Shigeta K, Morton LT, Sepulveda S, Wan L, Joseph R, Minogue E, Khatri A, Bardia A, Ellisen LW, Corcoran RB, Hata AN, Pai SI, Jain RK, Fukumura D, Duda DG, Cobbold M

Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy.

Nat Biotechnol. 2020;38(4):420-425 - PMID: 32042168 - PMCID: PMC7456461 - DOI: 10.1038/s41587-019-0404-8
Kong N, Tao W, Ling X, Wang J, Xiao Y, Shi S, Ji X, Shajii A, Gan ST, Kim NY, Duda DG, Xie T, Farokhzad OC, Shi J

Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition.

Sci Transl Med. 2019;11(523):ePub - PMID: 31852795 - PMCID: PMC7024563 - DOI: 10.1126/scitranslmed.aaw1565
Shigeta K, Datta M, Hato T, Kitahara S, Chen IX, Matsui A, Kikuchi H, Mamessier E, Aoki S, Ramjiawan RR, Ochiai H, Bardeesy N, Huang P, Cobbold M, Zhu AX, Jain RK, Duda DG

Dual PD-1 and VEGFR-2 blockade promotes vascular normalization and enhances anti-tumor immune responses in HCC.

Hepatology. 2020;71(4):1247-1261 - PMID: 31378984 - PMCID: PMC7000304 - DOI: 10.1002/hep.30889
Hong TS, Grassberger C, Yeap BY, Jiang W, Wo JY, Goyal L, Clark JW, Crane CH, Koay EJ, Dima S, Eyler CE, Popescu I, DeLaney TF, Zhu AX, Duda DG

Pretreatment plasma HGF as potential biomarker for susceptibility to radiation-induced liver dysfunction after radiotherapy.

NPJ Precis Oncol. 2018;2:22 - PMID: 30374460 - PMCID: PMC6194077 - DOI: 10.1038/s41698-018-0065-y
Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, Nellore V, Kongpetch S, Ng AWT, Ng LM, Choo SP, Myint SS, Thanan R, Nagarajan S, Lim WK, Ng CCY, Boot A, Liu M, Ong CK, Rajasegaran V, Lie S, Lim AST, Lim TH, Tan J, Loh JL, McPherson JR, Khuntikeo N, Bhudhisawasdi V, Yongvanit P, Wongkham S, Totoki Y, Nakamura H, Arai Y, Yamasaki S, Chow PKH, Chung AYF, Ooi LLPJ, Lim KH, Dima S, Duda DG, Popescu I, Broet P, Hsieh SY, Yu MC, Scarpa A, Lai J, Luo DX, Carvalho AL, Vettore AL, Rhee H, Park YN, Alexandrov L, Gordan R, Rozen SG, Shibata T, Pairojkul C, Teh BT, Tan P

Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.

Cancer Discov. 2017;7(10):1116-1135 - PMID: 28667006 - PMCID: PMC5628134 - DOI: 10.1158/2159-8290.CD-17-0368
Popp I, Grosu AL, Niedermann G, Duda DG

Immune modulation by hypofractionated stereotactic radiation therapy: Therapeutic implications.

Radiother Oncol. 2016;120(2):185-94 - PMID: 27495145 - DOI: 10.1016/j.radonc.2016.07.013
Hato T, Zhu AX, Duda DG

Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma.

Immunotherapy. 2016;8(3):299-313 - PMID: 26865127 - PMCID: PMC5619018 - DOI: 10.2217/imt.15.126
Chen Y, Ramjiawan RR, Reiberger T, Ng MR, Hato T, Huang Y, Ochiai H, Kitahara S, Unan EC, Reddy TP, Fan C, Huang P, Bardeesy N, Zhu AX, Jain RK, Duda DG

CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice.

Hepatology. 2015;61(5):1591-602 - PMID: 25529917 - PMCID: PMC4406806 - DOI: 10.1002/hep.27665
Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, Deshpande V, Shinagare S, Wo JY, Boucher Y, Wadlow RC, Kwak EL, Allen JN, Clark JW, Zhu AX, Ferrone CR, Mamon HJ, Adams J, Winrich B, Grillo T, Jain RK, DeLaney TF, Fernandez-Del Castillo C, Duda DG

A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation With Proton Beam Therapy and Capecitabine Followed By Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma.

Int J Radiat Oncol Biol Phys. 2014;89(4):830-8 - PMID: 24867540 - PMCID: PMC4791180 - DOI: 10.1016/j.ijrobp.2014.03.034
15