Academic Profile : Faculty

Photo_Yasunori Saheki.jpg picture
Assoc Prof Yasunori Saheki
Vice Dean (Faculty Affairs), Associate Professor, Cell Biology and Neuroscience
Associate Professor, Lee Kong Chian School of Medicine
Dr. Yasunori Saheki is an Associate Professor of Cell Biology and Neuroscience at Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore. He obtained his M.D. from Okayama University Medical School, Japan, in 2005 and his Ph.D. from The Rockefeller University, USA, in 2010 under the mentorship of Dr. Cori Bargmann. After finishing his postdoctoral training with Dr. Pietro De Camilli at Yale University, USA, he joined the faculty at LKCMedicine as a Nanyang Assistant Professor in 2016. In 2020, he was selected as a European Molecular Biology Organization (EMBO) Global Investigator. He was promoted to Associate Professor with Tenure in 2022. He was appointed as Assistant Dean for Faculty Affairs in 2023 and subsequently as Vice Dean for Faculty Affairs in 2024. He is also a Visiting Professor at the Institute of Resource Development and Analysis, Kumamoto University, Japan. He was awarded the National Research Foundation, Singapore (NRF) Investigatorship in 2024. His laboratory employs mammalian cell biology and C. elegans genetics to tackle fundamental questions in cellular lipid regulation as well as the mechanisms that underlie neurological disorders.
Lipid homeostasis plays a central role in membrane integrity, signalling and cell viability in all eukaryotic cells. Dynamic transfer of lipids from one cellular compartment to another functions in this process; however, our knowledge regarding the mechanisms that control lipid delivery remains limited. The long-term goal of our laboratory is to gain mechanistic insights into how cellular lipid compartmentalization is maintained and understand its role in specialized cells, particularly neuronal cells.

The Role of Lipids in Neurodegenerative Diseases & Ageing


Lipid Regulation at Membrane Contact Sites
In eukaryote, most membrane lipids are synthesised in the endoplasmic reticulum (ER). Vesicular transport, which employs membrane budding and fusion reactions, plays an important role in delivery of newly synthesiszed lipids to other membranes. However, growing evidence suggests a critical role of non-vesicular transport in lipid exchange at membrane contact sites between the ER and other membranous organelles as well as the plasma membrane (PM). Asst Prof Saheki’s lab aims to uncover the function of membrane contact sites, with particular focus on ER-PM contacts, in order to advance our knowledge in lipid homeostasis.

Lipid Homeostasis in Neuronal Cells
Neuronal cells extend multiple processes for efficient neurotransmission; synaptic membranes are highly dynamic and can be separated from the cell body by a significant distance. At distant nerve terminals, vesicular transport is not sufficiently rapid to replenish the loss of PM lipids. Neuronal processes, including axons and dendrites, are highly decorated with a continuous network of the ER. Therefore, non-vesicular lipid transport via ER-PM contacts is likely to have significant roles in maintenance of the neuronal PM. Significantly, mutations in ER morphogenetic proteins have been identified in neurodegenerative disorders, including motor neuron diseases. Asst Prof Saheki’s working hypothesis is that lipid regulation at ER-PM contacts is critical for the viability of neurons with particularly long axons, including motor neurons. His lab aims to elucidate the basic principle of lipid homeostasis in neuronal cells and uncover the mechanisms of the progression of neurodegeneration.

Links to Neurodegeneration
Investigating the mechanisms of lipid exchange at membrane contact sites is fundamental to our understanding of cellular lipid homeostasis, and our findings will have broad implications. Moreover, recent human genetic studies revealed the strong link between dysfunction of membrane contact sites and various types of neurodegenerative disorders, including Parkinson’s disease and Alzheimer’s disease. Therefore, our research may contribute to the development of potentially new treatments for neurodegeneration.
 
  • Investigating the importance of cholesterol homeostasis for neuronal function
  • Understanding the molecular mechanisms of intracellular cholesterol trafficking using a novel cholesterol biosensor
  • EMBO Global Investigator Network (GIN)- Yasunori Saheki
  • Human NLRP1 as a nuclear dsRNA sensor
  • Unravelling the Age-old Question on How Neurons Distribute Cholesterol within the Cell
  • Mechanism-based design of programmable nanoparticle delivery vehicles for RNA therapeutics: controlling endosomal escape
Awards
NRF Investigatorship (2024)
Dean's Award for Research (2022)
EMBO Global Investigatorship (2020)
Nanyang Assistant Professorship (2016)
 
Fellowships & Other Recognition
Japan Society for the Promotion of Science Overseas Research Fellowship (2013)
Uehara Memorial Foundation Research Fellowship (2012)
The Nakajima Foundation Graduate Student Fellowship (2005)
 
Supervision of PhD Students
• Minyoung Na (ongoing)
• Haoning Yang (ongoing)
• Dylan Hong Zheng Koh (PhD conferred in August 2024)
• Nur Raihanah Binte Mohd Harion (PhD conferred in July 2023)
• Darshini Jeyasimman (PhD conferred in September 2021)