Takaharu Ichimura, PhD

Instructor in Medicine
My principal effort at BWH and HMS is in basic research, with a focus on kidney diseases. I also have a supervising responsibility in Dr. Bonventre’s research group with the remaining time devoted to teaching the rest of division members, other administrative tasks, and peer-review.

Area of Excellence: I have been working on following three research field: 1) Characterization of kidney Injury Molecule –1 (KIM-1) which is a molecule functions as a cell binding receptor, phagocytosis and scavenger receptor, and also modulate cytoprotection and inflammatory response.  2) Functional characterization of activated macrophage molecule membrane protein Gpnmb. My total 83 publications appeared on Google Scholar (as of 1/2/20) have been cited total 5,996 times, with h-index = 29 and h10-index = 41, during the period of 1988 to 2020.  My 1998 JBC paper alone has been cited for 1126 times.

During my thesis study, I characterized expression of a group of genes and proteins belong to the families of fibroblast growth factors and their receptors in nephrotoxicant injured and regenerating rat kidneys. I extended analysis of the growth factor and receptor gene expression to the developing rat kidneys in embryo using RNA in situ hybridization technique. I also analyzed production of the fibroblast growth factor like activities in transformed rat renal proximal tubule cells in culture. I also applied immunohistochemical technique for detecting the nephrotoxicant protein adducts in situ. My immunohistochemial analysis for detection of a protein-adduct from PhD thesis study was used for a figure in a Nephrology textbook (Atlas of Kidney Disease).

As a postdoctoral fellow, I cloned renal injury related genes, Kidney Injury Molecule –1 (KIM-1) also known as Tim-1, and gpnmb, which are type-1 membrane proteins and highly upregulated in injured kidneys, during my postdoctoral training. I employed Representational Difference Analysis (RDA) subtraction as a cloning strategy in this project. I observed high levels of both mRNA and protein expression of both genes as shown by several different analytical techniques including RNA in situ hybridization. I also found that the KIM-1 mRNA was upregulated in some human renal cell carcinoma tissues. I produced expression constructs for human Ig Fc tagged soluble human and rat Kim-1 proteins for application to FACS analysis of KIM-1 protein binding to various types of cells and administration to rats. I led a project for generation of kim-2 knock-out / gal-4-knock-in mice. Now KIM-1 is well recognized kidney injury biomarker and a search of PubMed by term “Kim-1 or Tim-1” gives 1034 papers. A Google Scholar search of a term “kidney injury molecule -1” has given 59,100 results (as of 6/23/17).

While working in my current position, I described Kim-1 protein expression in various types of nephrotoxicant induced renal injury models, including detection of Kim-1 protein as a biomarker in the urine samples collected from toxicant treated rats.  I found that KIM-1 protein a novel receptor which mediates phagocytosis of apoptotic cells and a scavenger receptor for low density lipoproteins to the KIM-1 expressing LLC-PK1 renal epithelial cells. This work was reviewed two times in “Faculty of 1000” (FFa score = 12 and 8), and it was highlighted in a commentary. and also possesses cytopretective functions against oxidative stress.

I am currently focusing on the role of KIM-1 in renal epithelial cell injury and pro-inflammatory activation of macrophages and dendritic cells in ischemia induced acute kidney injury, lupus nephritis and diabetic nephropathy.

Teaching and Educational Contributions: I have also significantly contributed in setting up, training of users and maintain a division microscope facility in the Renal Division, Brigham and Women’s Hospital. I also have trained more than 250 division members (as of 2017) for operation of the division microscopes in the Microscope Core Facility (located at HIM550).

Summary:  I am a scientist active in laboratory investigation, translational research, and training of students, fellows and physician-scientists.  These activities occur at BWH, MGH, etc. and flow mainly through my focus on study of kidney diseases.