Molecular and Chemical Life Science :
Cooperative faculties


Professor MOTOHASHI Hozumi
Campus Seiryo campus
Laboratory Redox Biology
Tel +81-22-717-8550
E-mail hozumim@med.tohoku.ac.jp
Website http://www2.idac.tohoku.ac.jp/dep/ger/

I was born in Kagoshima and brought up in Sendai. After graduating from medical school, I got a training as an ENT doctor for 2 years. During my PhD course, I was fascinated with intricate regulatory mechanisms of transcriptional regulation and decided to switch my major to biochemistry. A main target of my current research is a redox-responsive transcription factor NRF2. My goal is to clarify in vivo contribution of NRF2 to various aging-related diseases, including cancer, chronic inflammation and neurodegeneration.

Selected Publications
  1. Akaike T, Ida T, Wei FY, Nishida M, Kumagai Y, Alam MM, Ihara H, Sawa T, Matsunaga T, Kasamatsu S, Nishimura A, Morita M, Tomizawa K, Nishimura A, Watanabe S, Inaba K, Shima H, Tanuma N, Jung M, Fujii S, Watanabe Y, Ohmuraya M, Nagy P, Feelisch M, Fukuto JM, Motohashi H.  Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics.  Nat Commun 8, 1177, 2017.
  2. Kitamura H, Onodera Y, Murakami S, Suzuki T, Motohashi H.  IL-11 contribution to tumorigenesis in an NRF2 addiction cancer model.  Oncogene 36, 6315-6324, 2017.
  3. Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, Tanaka N, Moriguchi T, Motohashi H, Nakayama K, Yamamoto M.  NRF2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription.  Nat Commun 7, 11624, 2016.
  4. Shirasaki K, Taguchi K, Unno M, Motohashi H, Yamamoto M.  Nrf2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice.  Hepatology 59, 2371-2382, 2014.
  5. Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, Yamamoto M, Motohashi H.  Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming.  Cancer Cell 22, 66-79, 2012. 
  6. Motohashi H, Kimura M, Fujita R, Inoue A, Pan X, Takayama M, Katsuoka F, Aburatani H, Bresnick EH, Yamamoto M.  NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation.  Blood 115, 677-686, 2010. 
  7. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou Y.-S., Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S.-i., Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M.  The selective autophagy substrate p62 activates the stress response transcription factor Nrf2 through inactivation of Keap1.  Nat Cell Biol 12, 213-223, 2010.
  8. Motohashi H, Katsuoka F, Engel JD, Yamamoto M.  Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway.  Proc Natl Acad Sci USA 101, 6379-6384, 2004.
  9. Kusunoki H, Motohashi H, Katsuoka F, Morohashi A, Yamamoto M and Tanaka T.  Solution structure of the DNA-binding domain of MafG.  Nat Struct Biol 4, 252-256, 2002.
  10. Motohashi H, Katsuoka F, Shavit JA, Engel JD, Yamamoto M.  Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins.  Cell 103, 865-875, 2000. 
Activities in Academic Societies
A member of Japanese Biochemical Society, Japanese Cancer Association, The Molecular Biology Society of Japan, and Society for Free Radical Research Japan. 

Transcriptional regulation in response to redox imbalance
Glucose metabolism and OXPHOS  

Recent Activities

A current major question in my lab is how the redox regulation contributes to the process of organismal aging.  Our hypothesis is that impaired environmental response and subsequent smoldering inflammation are two essential components of aged phenotypes.  To prove this hypothesis, we are conducting various experiments described below.  
 (1)  Impaired environmental response
Interaction with environments is a critical determinant of organismal aging processes.  Many of the environmental stresses alter the cellular redox balance, which eventually results in the organ dysfunction of aged individuals.  We are interested in the relation between anti-aging effects of habitual exercise and NRF2 function.  NRF2-driven metabolic reprogramming for energy production is one of the important themes in our current studies.   
 (2)  Smoldering inflammation
We are focusing on Alzheimer’s disease and chronic obstructive pulmonary disease (COPD), which are two major aging-related diseases.  We recently clarified that NRF2 has a potent anti-inflammatory activity and effectively alleviates a lethal autoimmune disease caused by Treg deficiency (Suzuki et al, Mol Cell Biol 2017).  Multiple experimental approaches are being taken for elucidating molecular mechanisms of NRF2-mediated suppression of inflammation.  

Message to Students

If you find a new reaction, always be aware how it is important in vivo.  There could be a lot of peculiar and novel phenomena you can find.  But it is very important to characterize the phenomena in the biological context because our ultimate goal is achievement of healthy aging of human beings.