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TUMOR MICROENVIRONMENT LABORATORY

Seoul National University
College of Veterinary Medicine

 

RESEARCH INTERESTS

We have diverse interests in Cancer/Radiation Biology and Inflamatory Diseases.  Here are only some of the in-depth projects currently undergoing in the lab. Since we're trying to pursue 'TRANSLATION RESEARCH' (i.e., clinical implication & applicability), please take a look at 'Collaborators' section below for more information on our latest research interests.

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GO GET EM TIGER!
BLOCK MACROPHAGES!

Macrophages are well known for their protumoral roles. Recently we have reported that macrophages can exacerbate tumor hypoxia and aerobic glycolysis. If they can consume oxygen and glucose, how will they regulate T cell functions and immunotherapy? How can we block macrophages? What signaling in macrophages is responsible for this phenomenon? We have all the know-hows and the newest mouse lung cancer model (ALK overexpression) mimicking patients in the lab to address this question!

FLASH, THE NEW RADIOTHERAPY ON THE BLOCK!

In the clinic, we treat tumors with radiotherapy using LINAC (linear accelerator), proton radiotherapy, or carbon (particle) radiotherapy. In collaboration with Stanford University, US, we are exploring novel biological mechanisms (effects in the tumor microenvironment) from the latest radiotherapy technique called FLASH. This is ultra-fast dose rate ionizing radiotherapy, which can deliver 20 Gy (very high dose of ionizing radiation) in just a couple of seconds!

YOUR FAT , YOUR GENE IN MACROPHAGES!

We have recently created novel myeloid-specific knockout mice in hypoxia-inducible factor (HIF) signaling pathway and found that these mice exhibit anti-obese phenotype. We're currently investigating the molecular mechanisms and seeing that it is Hif-alpha gene in macrophages regulating the diet-induced obesity. We're expanding this idea to Cancer Biology to see how macrophage could regulate fat metabolism in cancer cells.

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BETTER MOUSE MODEL FOR BETTER  IMMUNOTHERAPY TO TREAT LUNG CANCER!

Current response rate for the latest immunotherapy (PD-1 or PD-L1 bloackdes) in lung cancer patients (NSCLC) is only about 30%. To increase the effectiveness of immunotherapy, we need to understand how immune cells function and interact with each other during the lung cancer progression. We have a novel strain of mouse lung cancer mimicking NSCLC patients (ALK overexpressed tumors) to address this.

SEEING IS BELIEVING!

We are interested in the real-time in vivo imaging of macrophages (and other immune cells such as T cells) infiltrating into tumors using the dorsal (and intracranial) window chamber techniques that we have established in our lab. We can powerfully manipulate cancer cells so that they can express reporters upon metabolic/stress conditions. In addition, we can study the mechanisms of various anticancer modalities (such as DNA repair inhibitors,  checkpoint blockades, and anti-angiogenic agents) in live mice.

ARE YOU BREATHING?
OXYGEN-SENSING IN MACROPHAGES!

We have recently reported that tumor-associated macrophages (TAM) can compete with cancer cells for oxygen and glucose. Does hypoxia-inducible factor (HIF) regulate this mechanism? Does this occur in other metabolic diseases such as obsity and cancer cachexia? We have novel strains of mice targeting HIF pathways in macrophages to address this!

 

COLLABORATORS

SEOUL NATIONAL UNIVERSITY
COLLEGE OF MEDICINE

  • The effect of high dose radiotherapy (including FLASH) on the tumor microenvironment

  • Optimal treatment schedule for immunotherapy in combination with radiotherapy

  • Identifying the role of TIL (tumor-infiltrating lymphocytes) during the lung cancer progression

STANFORD UNIVERSITY
SCHOOL OF MEDICINE

  • Investigating the effect of FLASH on tumor microenvironment

  • Blocking strategies for macrophages to enhance antitumor immune response

  • Vascular Biology (middle cerebral artery occlusion surgery & femoral artery ligation surgery), Atherosclerosis (aorta anatomy and analyses), and Lipid Metabolism/Biology

DUKE UNIVERSITY
SCHOOL OF MEDICINE

  • Dorsal Window Chamber technique in mice

  • Tumor hypoxia, angiogenesis, intratumoral perfusion

UNIVERISTY OF PENNSYLVANIA
SCHOOL OF MEDICINE

  • Gamma H2AX,  tumor hypoxia

  • Mechanical aspects for FLASH irradiation on tumor microenvironment

KOREA UNIVERSITY
DEPARTMENT OF LIFE SCIENCE

  • Lipid metabolism

  • Adipocyte biology

  • Metabolism and Cancer

POSTECH
DEPARTMENT OF CHEMISTRY

  • Macrophage imaging agents

  • Quantum dots imaging tumor hypoxia

  • Nanoparticles controlling macrophage polarization

 

PUBLICATIONS

Major publications only

Feb 15, 2019

TUMOR-ASSOCIATED MACROPHAGES ENAHNCE TUMOR HYPOXIA AND AEROBIC GLYCOLYSIS

  • Jeong & Kim et al., Cancer Res (2019), 79(4):795-806

  • Hoibin Jeong received: 2016 POSCO CheongAm Graduate Fellowship, 2019 Best Research Paper in the Dept Life Science POSTECH

  • Chan-Ju Lee received 2015 Young Investigator Award (ICRR, Kyoto, Japan)

Jul 30, 2018

HIF-1A ACTIVATION IN MYELOID CELLS ACCELERATES DEXTRAN SODIUM SULFATE-INDUCED COLITIS PROGRESSION IN MICE

  • Kim et al., Dis Model Mech (2018) 11(7), pii:dmm033241

  • Young-Eun Kim received 2012 Global PhD Fellowship, 2015 Keystone Scholarship (Dublin, Ireland), 2018 KSMCB Best Poster Award (Seoul, Korea)

  • Jeongwoo Kim received 2016 Global PhD Fellowship

  • Sujin Yeo received 2014 Global PhD Fellowship

Dec 1, 2017

HYPOXIA-INDUCIBLE FACTOR-1A REGULATES MICROGLIAL FUNCTIONS AFFECTING NEURONAL SURVIVAL IN THE ACUTE PHASE OF ISCHEMIC STROKE IN MICE

  • Oncotarget (2017), 8(67), 111508-111521

  • Seoyeon Bok is currently doing her postdoctoral fellowship in Cornell University, US

Dec, 2016

TUMOR HYPOXIA AND REOXYGENATION: THE YIN AND YANG FOR RADIOTHERAPY

  • Hong et al., Radiat Oncol J (2016), 34(4), 239-249

  • Beom-Ju Hong received 2013 Global PhD Fellowship, 2015 Junior Investigator Award (ICRR, Kyoto, Japan), 2015 Best Poster Award (ICRR, Kyoto, Japan), 2017 Junior Investigator Award (Tumor Microenvironment Workshop, Florida, US)

Jul 1, 2016

RADIATION-INDUCED ESOPHAGITIS IN VIVO AND IN VITRO REVEALS THAT EPIDERMAL GROWTH FACTOR IS A POTENTIAL CANDIDATE FOR THERAPEUTIC INTERVENTION STRATEGY.

Kim & Jeon et al., Int J Radiat Oncol Biol Phys (2016), 95(3), 1032-1041

Jul 1, 2016

REAL-TIME TUMOR OXYGENATION CHANGES AFTER SINGLE HIGH-DISE RADIATION THERAPY IN ORTHOTOPIC AND SUBCUTANOUES LUNG CANCER IN MICE: CLINICAL IMPLICATION FOR STEREOTACTIC ABLATIVE RADIATION THERAPY SCHEDULE OPTIMIZATION.

Song & Hong et al., Int J Radiat Oncol Biol Phys (2016), 95(3), 1022-1031

Aug 7, 2015

IN VIVO IMAGING OF ACTIVATED MICROGLIA IN A MOUSE MODEL OF FOCAL CEREBRAL ISCHEMIA BY TWO-PHOTON MICROSCOPY

Bok et al., Biomed Opt Express (2015), 6(9), 3303-3312

Feb 18, 2014

TRANSCRIPTIONAL ACTIVATION OF HYPOXIA-INDUCIBLE FACTOR-1 (HIF-1) IN MYELOID CELLS PROMOTES ANGIOGENESIS THROUGH VEGF AND S100A8

Ahn et al., PNAS (2014), 111(7), 2698-2703

May 4, 2010

INHIBITION OF MAC-1 (CD11B/CD18) ENHANCES TUMOR RESPONSE TO RADIATION BY REDUCING MYELOID CELL RECRUITMENT

Ahn et al., PNAS (2010), 107(18), 8363-8368

Mar 2008

MATRIX METALLOPROTEINASE-9 IS REQUIRED FOR TUMOR VASCULOGENESIS BUT NOT FOR ANGIOGENESIS: ROLE OF BONE MARROW-DERIVED MYELOMONOCYTIC CELLS

Ahn & Brown, Cancer Cell (2008), 13(3), 193-205

Jun 14, 2006

RADIOLYTIC AND CELLULAR REDUCTION OF A NOVEL HYPOXIA-ACTIVATED COBALT (III) PRODRUG OF A CHLOROMETHYLBENZINDOLINE DNA MINOR GROOVE ALKYLATOR

Ahn et al., Biochem Pharmacol (2006), 71(12), 1683-1694

Sep 2004

OPTIMIZATION OF THE AUXILIARY LIGAND SHELL OF COBALT(III)(8-HYDROXYQUINOLINE) COMPLEXES AS MODEL HYPOXIA-SELECTIVE RADIATION-ACTIVATED PRODRUGS

Ahn et al., Radiat Res (2004), 162(3), 315-325

 

LAB MEMBERS

G-ONE AHN, PH.D.

PI (Lab Head)

  • 2019.09~present: Associate Professor, Seoul National University College of Veterinary Medicine

  • 2017.03~2017.09: Visiting Professor, Stem Cell Institute and Regenerative Medicine, Stanford University School of Medicine (Irving L. Weissman's lab)

  • 2015.09~2019.08: Associate Professor, Integrative Biosciences Biotechnology(IBB)/Life Science, POSTECH (Pohang University of Science and Technology)

  • 2011.04~2015.08: Assistant Professor, IBB, POSTECH

  • 2008.09~2011.03: Research Associate, Stanford University School of Medicine (Dept Radiation Oncology, J. Martin Brown's lab)

  • 2003.09~2008.08: Postdoc, Stanford University School of Medicine (Dept Radiation Oncology, J. Martin Brown's lab)

  • 2000.03~2003.08: Ph.D. in Pathology, The University of Auckland, Auckland, New Zealand (Auckland Cancer Society Research Centre, William R. Wilson's lab)

  • 1998.03~2000.02: M.Sc. (Hons) in Pharmacology, The University of Auckland, Auckland, New Zealand (Mark J. McKeage's lab)

  • 1995.03~1998.02: B.Sc. in Chemistry & Pharmacology, The University of Auckland, Auckland, New Zealand 

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TBA

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YOUR NAME HERE​

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PAST TME LAB AT POSTECH

Past lab members

From left to right, back to front

  • Ami-Marie Coulibaly

  • John Chulhoon Park

  • Rumeysa Dogan

  • Young-Eun Kim

  • Jung-Min Oh

  • Hyeong-Seok Choi

  • G-One Ahn

  • Hye-Jung Gu

  • Hoibin Jeong

  • Seunghee Gwak

 

문의하기/ENQUIRY

서울시 관악구 관악로 1, 서울대학교 수의과대학 85동 705호
Rm 705, Building 85
College of Veterinary Medicine
Seoul National University
1 Gwanak-ro, Gwanak-gu
Seoul 08826, Korea

02-880-1297