Doctoral Defense in Biomedical and Health Sciences - Kijin Jang

On Friday, May 22, Kijin Jang will defend her doctoral dissertation in Biomedical and Health Sciences at the Faculty of Medicine of the University of Iceland. The dissertation is titled: Skýring á stjórnunarneti svörunar við vægri ofkælingu. Elucidation of the regulatory network orchestrating the mild hypothermia response.

The opponents are Dr. Lykke Sylow, Professor at the University of Copenhagen, and Dr. Ólafur Eysteinn Sigurjónsson, Professor at Reykjavík University.

The supervisor and advisor was Professor Hans Tómas Björnsson. In addition to him, the doctoral committee included Professor Eiríkur Steingrímsson, Professor Margrét Helga Ögmundsdóttir, Professor Zophonías Oddur Jónsson, and Professor Emeritus Þór Eysteinsson.

Sædís Sævarsdóttir, Professor and Dean of the Faculty of Medicine, will preside over the ceremony, which will take place in the Ceremonial Hall of the University of Iceland and begin at 9:00 a.m.

Abstract
Therapeutic hypothermia is a well-established neuroprotective strategy following pathological conditions such as acute brain injury. However, its clinical implementation is frequently hindered by physiological adverse effects and logistical complexity. Pharmacological mimetics that can trigger the activation of the mild hypothermia response (MHR) under normothermic conditions without physical cooling offer a promising alternative to conventional strategies.
Through genome-scale CRISPR-Cas9 and siRNA-based screens, this study identifies SMYD5 and SARAF as novel, targetable repressors of the MHR. We demonstrate that SMYD5 is a temperature-sensitive SP1 repressor that undergoes rapid proteasomal degradation in response to mild hypothermic exposure to initiate the MHR. Furthermore, we characterise SARAF (also known as TMEM66) as a critical, temperature-sensitive regulator of the MHR-induced genes SP1 and RBM3, demonstrating that its inhibitory role is more pronounced under normothermic conditions than under mild hypothermic conditions. Our findings reveal that SARAF silencing significantly upregulates both genes at the transcriptional and translational levels and confers cytoprotective effects whilst reducing apoptosis under hypoxic conditions. We further identify the transcription factor JUN as the essential link in the SARAF-SP1/RBM3 axis. Collectively, this study delineates a hierarchical regulatory landscape of the MHR and establishes SMYD5 and SARAF as inhibitory nodes that can be targeted to achieve the clinical benefits of therapeutic hypothermia under normothermic conditions.

About the doctoral candidate
Kijin Jang completed a BSc degree in Life Sciences from the Catholic University of Korea in Seoul, South Korea, and an MSc degree in Molecular Medicine at the Faculty of Medicine at NTNU (Norwegian University of Science and Technology) in Trondheim, Norway. Her master’s thesis, conducted within the Department of Clinical and Molecular Medicine (IKOM) at NTNU, focused on the analysis of whole-exome sequencing data to identify novel and rare variants in susceptibility genes associated with hereditary colorectal cancer.

Since 2022, Kijin has pursued doctoral studies at the Faculty of Medicine of the University of Iceland under the supervision of Professor Hans Tómas Björnsson, physician and PhD. Kijin is the daughter of Yeonggeun Jang and Yoonhwan Kim, and the sister of Chowon Jang.