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
MD ANDERSON CANCER CENTER
10
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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