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1. Research direction and laboratory introduction. （）

The kidney systems biology center (KidSBC), headed by Hiroaki Kikuchi, MD, PhD, exploits a unique combination of high-level experimental and computational methodologies to produce research on mechanisms of kidney diseases.

A central element of KidSBC research portfolio is a project designed to identify every gene expressed in every epithelial cell type of the kidney using modern transcriptomic and proteomic techniques.

A second important element of Dr. Kikuchi’s work aims to understand the mechanisms underlying development of chronic kidney diseases. 

A third important element of Dr. Kikuchi’s research is designed to understand syndromes associated with excess water retention by the kidneys. 

We focused on AMP-activated protein kinase (AMPK), which plays a crucial role as an energy sensor. AMPK is a serine/threonine kinase that functions as a key energy sensor in cells.
Using metabolome analysis of renal parenchyma, we discovered that in chronic kidney disease (CKD), the AMP/ATP ratio is elevated, leading to an intracellular energy deficiency. 
Furthermore, we found that AMPK fails to accurately sense the increased AMP/ATP ratio. 

2. Profile of key leaders. 

Hiroaki Kikuchi has been working on elucidating the pathophysiology of chronic kidney disease (CKD) and developing novel therapeutic strategies from both clinical and basic research perspectives. 
Dr. Kikuchi was involved in establishing a unique cohort study at Tokyo Medical and Dental University (the CKD-ROUTE study), where he demonstrated that low body weight and hypoalbuminemia are strongly associated with poor renal prognosis (Clin Exp Nephrol. 2017). 
Furthermore, through a retrospective cohort multivariate analysis using a nationwide clinical database in Japan, he revealed that low body weight is correlated with poor survival outcomes in CKD patients (PLoS One. 2018).
During his doctoral studies at the Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Dr. Kikuchi conducted integrated analyses of metabolomics and RNA-seq using kidney tissue samples. 
He discovered that energy metabolism dysfunction is a prominent feature in CKD kidneys. 
He further elucidated the molecular mechanism underlying this dysfunction, identifying that AMP-activated protein kinase (AMPK), a central intracellular energy sensor, fails to properly sense energy status in CKD kidneys (Kidney Int. 2019).
After completing his Ph.D., Dr. Kikuchi joined the Epithelial Systems Biology Laboratory at the National Institutes of Health (NIH) as a JSPS Overseas Research Fellow. 
There, he successfully developed the first-ever Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) using isolated renal tubules. Through this work, he identified PPARα, a master regulator of lipid metabolism, as a key factor involved in compensatory hypertrophy of proximal tubules (Nat Commun. 2023). He also mastered integrative analysis methods for multi-omics data using Bayesian theory and uncovered mechanisms regulating the expression of the aquaporin water channel (AQP2) (Am J Physiol Renal Physiol. 2021). During his time in the U.S., Dr. Kikuchi continued to mentor graduate students at Tokyo Medical and Dental University, significantly contributing to the completion of several doctoral dissertations.
After returning to Japan, Dr. Kikuchi made a groundbreaking discovery that ULK1 (unc-51 like autophagy activating kinase 1) regulates the binding of AMP to AMPK through phosphorylation of the AMPK-γ subunit at Ser260/Thr262. 
This finding further deepened the understanding of energy metabolism dysfunction in CKD kidneys (Kidney Int. 2024).