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Assistant Professor

Department of Developmental Biology
Molecular Genetics Program
Computational Biology Program
Developmental Biology Program

Research Interests

In our current society, we are paying much more attention to aging than ever. Based on the Census Bureau’s prediction, more than 800,000 baby boomers will celebrate their 100th year by the middle of the 21st century. However, the molecular mechanism of aging and longevity is still poorly understood. The primary interest in our laboratory is the molecular mechanism of mammalian aging and longevity. We are currently focusing on the following subjects:

1) Mammalian Sir2. I have found that S. cerevisiae Sir2p and its higher eukaryotic orthologs are novel nicotinamide adenine dinucleotide (NAD)-dependent histone/protein deacetylases. Sir2 proteins promote longevity in yeast and in C. elegans by silencing rDNA and regulating the insulin/IGF-1 signaling pathway, respectively. The enzymatic activities and functions of Sir2 proteins are highly conserved in evolution. My lab is examining whether the mammalian Sir2 ortholog regulate aging and affect longevity in mammals. We are addressing this question by combining mouse genetics with cell biological and computational approaches.

2) Aging-related diseases. My lab is particularly interested in diabetes and cancer. Like in C. elegans, Sir2 may be also involved in the regulation of glucose metabolism in mammals. We are currently studying the function of the mammalian Sir2 ortholog in insulin-producing pancreatic b cells. Moreover, we have recently found that mammalian Sir2 negatively regulates the p53 function by physically interacting with and deacetylating the protein. This aspect of Sir2 function may connect various cellular damages, such as oxidative stress, to aging and carcinogenesis.

3) NAD metabolism. NAD is not only a co-substrate for Sir2 but essential for a variety of biological processes. However, the pathways that regulate NAD production and compartmentalization in mammalian cells remain ill-defined. Identifying and characterizing the principal enzymes involved in mammalian NAD biosynthetic pathways will set the stage for subsequent genetic manipulations of NAD levels in selected cell lineages and assessment of the impact of such manipulations on the aging process.

Imai Biosketch

Education and Professional Experience:

  • Assistant Professor, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 2001-present.
  • Postdoctoral Fellow/Associate, Massachusetts Institute of Technology, Department of Biology, 1997-2001.
    Postdoctoral Adviser: Dr. Leonard Guarente
  • Instructor, Keio University School of Medicine, Department of Microbiology, 1993-1997.
  • Ph.D., Keio University Graduate School of Medicine, Tokyo, Japan, 1989-1993.
    Thesis Supervisor: Dr. Toshiya Takano
  • M.D., Keio University School of Medicine, Tokyo, Japan, 1983-1989

Honors and Awards

  • Ellison Medical Foundation New Scholar Award in Aging, 2003-2007
  • The Leukemia and Lymphoma Society Special Fellow, 2001-2004
  • The Human Frontier Science Program Long-Term Fellow, 1997-1999
  • The American Society for Cell Biology/Glenn Foundation Award, 1996
  • Keio University Sakaguchi-Memorial Medical Science Fund, 1996
  • Keio University School of Medicine Alumni Association Award, 1995
  • Predoctoral Award from Keio University School of Medicine, 1990-1991


Selected Publications

Christopher M. Armstrong, Matt Kaeberlein, Shin-ichiro Imai, and Leonard Guarente. 2002. Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silecing phenotypes and in vitro histone deacetylation activity. Mol. Biol. Cell 13: 1427-1438.

Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W. Negative control of p53 by Sir2a promotes cell survival under stress. Cell 2001 107: 137-148.

Vaziri H, Dessain SK, Eaton EN, Imai S, Frye RA, Pandita TK, Guarente L, Weinberg RA. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 2001 107: 149-159.

Imai S, Johnson FB, Marciniak RA, McVey M, Park PU, Guarente L. Sir2: An NAD-dependent histone deacetylase that connects chromatin silencing, metabolism, and aging. Cold Spring Harbor Symp Quant Biol 2000 65:297-302.

Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000 403:795-800.

Imai S, Kitano H. Heterochromatin islands and their dynamic reorganization: a hypothesis for three distinctive features of cellular aging. Exp Gerontol 1998 3:555-570.

Kitano H, Imai, S. The two-process model of cellular aging. Exp Gerontol 1998 33:393-419.

Contact Information

Shin-ichiro Imai
Department of Molecular Biology and Pharmacology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
Rm 354, McDonnell Science Bldg.
St. Louis, MO 63110-1093
(Lab) 314-747-1031
(Office) 314-362-7228
(Fax) 314-362-7058
imaishin@wustl.edu

Developmental Biology Program Website

http://molecool.wustl.edu/DevBiol/






 
  
 
 
 
 
 
 
 
 
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
     
     
     
     
     
     
     
     
       
   
 
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