Role of HIF2 signaling in small intestine regeneration afte…

Role of HIF2 signaling in small intestine regeneration after radiation injury

Neeraj Kumari, PhD Post-Doc Fellow

Radiation Oncology Research Mentor : Dr. Cullen M. Taniguchi

MD ANDERSON CANCER CENTER

10/24/22

Gastrointestinal -ARS

Symptoms appears within few hours to days

Exposure Time of Onset Manifestation 5 - 12 Gy 9 - 10 days Gastrointestinal (GI) syndrome

The Intestinal Crypt

Chernobyl (HBO, 2019)

Stem cell

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10/24/22

There are no approved treatments for GI-ARS

FG-4592- an oral HIF activator

FDA approved for Anemia treatment and could be rapidly repurposed

tissue regeneration

Hypoxia Inducible Factors (HIFs)

stem cell growth

epithelial integrity

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FG-4592 induces intestinal stem cells markers

FG-4592

Veh FG-4592 Veh + 5 Gy FG-4592 + 5 Gy

⇧ intestinal stem

+4 stem cell markers

72h

Veh FG-4592 Veh + 5 Gy FG-4592 + 5 Gy

cell/crypt survival

+4 Quiescent stem cell marker

✱✱✱

✱✱✱✱

✱✱✱✱

✱✱ ✱

✱✱✱✱

Intestinal Organoid (Mini-Guts)

GI radioprotection

20

15

+4 Quiescent stem cell marker

✱✱✱

10

✱✱✱✱

✱✱✱✱

5

✱✱ ✱

✱✱✱✱

20

0

BMI

HOPX

DCLK1

MEX3A

TERT

15

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4

Acknowledgements Cullen Taniguchi, MD, PhD

Carolina Garcia, PhD Robert Fuentes, PhD Matthew Cribb, PhD Tara Fujimoto Maya Ferell Emily Caggiano Abagail Delahoussaye Jasper Chen

MD ANDERSON CANCER CENTER Thank you for your attention…….

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