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Contact information

Email
amato.giaccia@oncology.ox.ac.uk

Research Theme

Tumour Microenvironment (Co-Investigator)

Amato Giaccia

Professor of Radiation Oncology

Jack, Lulu & Sam Willson Professor in Cancer Biology

Research Summary

My research program is focused on translating basic science findings on the role of hypoxia in tumour progression and resistance to therapy to pre-clinical models of cancer that I ultimately hopes to take into the clinic. My overarching hypothesis is that hypoxia not only makes tumour cells resistant to radiotherapy, chemotherapy and in some cases targeted therapy, but also increases their invasiveness and metastatic potential by inducing a select group of genes involved in tissue remodeling.

Biography

Until moving to Oxford, Amato was “Jack, Lulu and Sam Willson Professor in Cancer Biology” in the Stanford University School of Medicine, Professor of Radiation Oncology, Associate Chair for Research & Director of the Division of Radiation & Cancer Biology in the Department of Radiation Oncology at Stanford University, California. He was the Director of Basic Science at the Stanford Cancer Institute and lead the Radiation Biology Program in Stanford’s Cancer Center, and was Director of the Cancer Biology Interdisciplinary Graduate Program.

He was awarded an American Cancer Society Junior Faculty Research Award and the Michael Fry Award from the Radiation Research Society for his outstanding contributions on understanding the molecular mechanisms of resistance promoted by the tumor microenvironment. Additionally, he was the recipient of the 2013 ASTRO Gold Medal. In 2015, he was awarded an NIH R35 Outstanding Investigator Award and was inducted into the National Academy of Medicine.

He co-authored the sixth, seventh & eighth editions of the textbook, “Radiation Biology for the Radiologist,” with Professor Eric Hall from Columbia.

Recent publications

Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.

Estephan H. et al, (2025), EMBO J, 44, 903 - 922

Therapeutic targeting of the functionally elusive TAM receptor family.

Miao YR. et al, (2024), Nat Rev Drug Discov, 23, 201 - 217

Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1.

Beach C. et al, (2023), J Clin Invest, 133

ACSL3 regulates lipid droplet biogenesis and ferroptosis sensitivity in clear cell renal cell carcinoma.

Klasson TD. et al, (2022), Cancer Metab, 10

The Combination of Radiotherapy and Complement C3a Inhibition Potentiates Natural Killer cell Functions Against Pancreatic Cancer.

Sodji QH. et al, (2022), Cancer Res Commun, 2, 725 - 738

C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models.

Nandagopal S. et al, (2022), Cancer Immunol Res, 10, 245 - 258

Neutralization of PD-L2 is Essential for Overcoming Immune Checkpoint Blockade Resistance in Ovarian Cancer.

Miao YR. et al, (2021), Clin Cancer Res, 27, 4435 - 4448

Wounds Inhibit Tumor Growth In Vivo.

Hu MS. et al, (2021), Ann Surg, 273, 173 - 180

Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations.

Aguilera TA. et al, (2020), Clin Cancer Res, 26, 2972 - 2985

An Activatable NIR Fluorescent Rosol for Selectively Imaging Nitroreductase Activity.

Klockow JL. et al, (2020), Sens Actuators B Chem, 306

Retraction Note: Lysyl oxidase is essential for hypoxia-induced metastasis.

Erler JT. et al, (2020), Nature, 579

Acetate supplementation restores chromatin accessibility and promotes tumor cell differentiation under hypoxia.

Li Y. et al, (2020), Cell Death Dis, 11

Irradiation or temozolomide chemotherapy enhances anti-CD47 treatment of glioblastoma.

Gholamin S. et al, (2020), Innate Immun, 26, 130 - 137

S100A10 Is a Critical Mediator of GAS6/AXL-Induced Angiogenesis in Renal Cell Carcinoma.

Xiao Y. et al, (2019), Cancer Res, 79, 5758 - 5768

HILPDA Regulates Lipid Metabolism, Lipid Droplet Abundance, and Response to Microenvironmental Stress in Solid Tumors.

VandeKopple MJ. et al, (2019), Mol Cancer Res, 17, 2089 - 2101

Lambda-Carrageenan Enhances the Effects of Radiation Therapy in Cancer Treatment by Suppressing Cancer Cell Invasion and Metastasis through Racgap1 Inhibition.

Wu P-H. et al, (2019), Cancers (Basel), 11

Suppressing Mitochondrial Respiration Is Critical for Hypoxia Tolerance in the Fetal Growth Plate.

Yao Q. et al, (2019), Dev Cell, 49, 748 - 763.e7

Targeting the Tumor Microenvironment in Radiation Oncology: Proceedings from the 2018 ASTRO-AACR Research Workshop.

McGee HM. et al, (2019), Clin Cancer Res, 25, 2969 - 2974

Endothelial Hypoxia-Inducible Factor-2α Is Required for the Maintenance of Airway Microvasculature.

Jiang X. et al, (2019), Circulation, 139, 502 - 517

Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual.

Merceron C. et al, (2019), Bone Res, 7

The tumour microenvironment links complement system dysregulation and hypoxic signalling.

Olcina MM. et al, (2019), Br J Radiol, 92

Acetate supplementation eliminates hypoxia mediated resistance to differentiation therapy in neuroblastoma cells

Li Y. et al, (2019), CANCER RESEARCH, 79

The irradiated tissue microenvironment and its role in breast cancer recurrence: Enhanced macrophage infiltration promotes tumor cell recruitment

Hacker BC. et al, (2019), CANCER RESEARCH, 79

Papaverine and its novel derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism

Benej M. et al, (2019), CANCER RESEARCH, 79

Mutations in an Innate Immunity Pathway Are Associated with Poor Overall Survival Outcomes and Hypoxic Signaling in Cancer.

Olcina MM. et al, (2018), Cell Rep, 25, 3721 - 3732.e6

Correction for Benej et al., Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism.

(2018), Proc Natl Acad Sci U S A, 115

Generation of Stable Expression Mammalian Cell Lines Using Lentivirus.

Tandon N. et al, (2018), Bio Protoc, 8

Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity.

Chen X. et al, (2018), Nat Commun, 9

Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism.

Benej M. et al, (2018), Proc Natl Acad Sci U S A, 115, 10756 - 10761

Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence following Radiotherapy in Immunosuppressed Patients.

Rafat M. et al, (2018), Cancer Res, 78, 4241 - 4252

A Human Genome-Wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1α-XBP1 Activation.

Yang Z. et al, (2018), Mol Cancer Res, 16, 745 - 753

PHD-2 Suppression in Mesenchymal Stromal Cells Enhances Wound Healing.

Ko SH. et al, (2018), Plast Reconstr Surg, 141, 55e - 67e

Radiation increases invasive activity of breast cancer cells via altering lysosome exocytosis

Wu P-H. et al, (2018), CANCER RESEARCH, 78

Carrageenan improves radiation therapy via integrin related molecular mechanism in cancer cell lines and in vivo.

Wu P. et al, (2018), MOLECULAR BIOLOGY OF THE CELL, 29

Involvement of Rab27 in radiosensitivity of glioblastoma cells

Nishioka S. et al, (2018), MOLECULAR BIOLOGY OF THE CELL, 29

Long-range hypoxia signaling in NAFLD.

LaGory EL. and Giaccia AJ., (2017), Nat Med, 23, 1251 - 1252

Stress-responsive HILPDA is necessary for thermoregulation during fasting.

VandeKopple MJ. et al, (2017), J Endocrinol, 235, 27 - 38

BLIMP1 Induces Transient Metastatic Heterogeneity in Pancreatic Cancer.

Chiou S-H. et al, (2017), Cancer Discov, 7, 1184 - 1199

Hypoxia and Bone Metastatic Disease.

Johnson RW. et al, (2017), Curr Osteoporos Rep, 15, 231 - 238

Molecular Pathways: Oncologic Pathways and Their Role in T-cell Exclusion and Immune Evasion-A New Role for the AXL Receptor Tyrosine Kinase.

Aguilera TA. and Giaccia AJ., (2017), Clin Cancer Res, 23, 2928 - 2933

Pre-metastatic niches: organ-specific homes for metastases.

Peinado H. et al, (2017), Nat Rev Cancer, 17, 302 - 317

KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage.

Castellini L. et al, (2017), Nucleic Acids Res, 45, 3674 - 3692

Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location.

Vilalta M. et al, (2017), Mol Imaging Biol, 19, 215 - 224

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies.

Kariolis MS. et al, (2017), J Clin Invest, 127, 183 - 198

Metabolic Alterations in Cancer and Their Potential as Therapeutic Targets.

Weyandt JD. et al, (2017), Am Soc Clin Oncol Educ Book, 37, 825 - 832

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells.

Wu P-H. et al, (2017), Int J Nanomedicine, 12, 5069 - 5085

Best of both worlds: can novel pathways be targeted for reduced gut toxicity but improved tumour response?

Olcina MM. et al, (2017), RADIOTHERAPY AND ONCOLOGY, 123, S40 - S41

Impairment of Mitochondrial Respiration Promotes Survival of Hypoxic Chondrocytes In Vivo.

Yao Q. et al, (2017), JOURNAL OF BONE AND MINERAL RESEARCH, 32, S1 - S1

Reprogramming the immunological microenvironment through radiation and targeting Axl.

Aguilera TA. et al, (2016), Nat Commun, 7

Hypoxia and metastasis

Finger EC. and Giaccia AJ., (2016), 69 - 100

A New Chromatin-Cytoskeleton Link in Cancer.

Giaccia AJ., (2016), Mol Cancer Res, 14, 1173 - 1175

Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy.

Chang ACY. et al, (2016), Proc Natl Acad Sci U S A, 113, 13120 - 13125

The Receptor Tyrosine Kinase AXL in Cancer Progression.

Rankin EB. and Giaccia AJ., (2016), Cancers (Basel), 8

Erratum: Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow.

Johnson RW. et al, (2016), Nat Cell Biol, 18

Reducing radiation-induced gastrointestinal toxicity - the role of the PHD/HIF axis.

Olcina MM. and Giaccia AJ., (2016), J Clin Invest, 126, 3708 - 3715

Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow.

Johnson RW. et al, (2016), Nat Cell Biol, 18, 1078 - 1089

Identification of Doxorubicin as an Inhibitor of the IRE1α-XBP1 Axis of the Unfolded Protein Response.

Jiang D. et al, (2016), Sci Rep, 6

Acridine Derivatives as Inhibitors of the IRE1α-XBP1 Pathway Are Cytotoxic to Human Multiple Myeloma.

Jiang D. et al, (2016), Mol Cancer Ther, 15, 2055 - 2065

Hypoxia: Signaling the Metastatic Cascade.

Rankin EB. et al, (2016), Trends Cancer, 2, 295 - 304

Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma.

Zhou L. et al, (2016), Oncogene, 35, 2687 - 2697