Dr. Mohammad Fazlul Karim
Dept. of Biotechnology and Genetic Engineering
Scientific Accomplishments & Research Interests
I have received my PhD from Department of Medical Biochemistry, Kumamoto University, Japan in September 27, 2013. The title of my dissertation was “Regulation of Cellular Metabolism by Nuclear Proteins”. My doctoral and postdoctoral study is increasingly attracting me to explore findings that can be helpful in preventing aging. I have been performing research on aging since 2012. I am studying how Sirt7, a member of sirtuin family, regulates various biological functions. Sirt7 is a NAD+ deacetylase that removes acetyl group from histone H3K18, which is important for maintaining the fundamental properties of the cancer cell phenotype and stabilizing the tumorigenicity of human cancer. I have identified Myb-binding protein 1a (Mybbp1a) as a novel negative regulator of Sirt7 (Biochem. Biophys. Res. Commun. 2013). I have also found that Sirt7 is associated with ubiquitin ligase complex which is important in controlling hepatic lipid metabolism. I have revealed that Sirt7 deacetylates damage specific DNA binding protein 1 (DDB1) and regulates TR4 (a transcription factor involved in lipid metabolism) degradation (Cell Metabolism 2014, Biochem. Biophys. Res. Commun. 2017). Besides, I have many other works in exploring function of proteins which are also associated with metabolic diseases. I worked to analyze the function of Anks4b which is identified as a novel target of HNF4α in pancreatic β-cells. I found that Anks4b binds with GRP78 and plays a significant role in the regulation of endoplasmic reticulum (ER) stress (J. Biol. Chem. 2012).
Now my major research focus is on the study of post translational modification (PTM) that plays an important role in regulation of protein function in various metabolic diseases including diabetes and fat induced liver diseases.
- Korogi W, Yoshizawa T, Karim MF, Tanoue H, Yugami M, Sobuz SU, Hinoi E, Sato Y, Oike Y, Mizuta H, Yamagata K. SIRT7 is an important regulator of cartilage homeostasis and osteoarthritis development. Biochem. Biophys. Res. Commun. 2018, In Press.
- Karim MF, Yoshizawa T, Sobuz SU, Sato Y, Yamagata K. Sirtuin 7-dependent deacetylation of DDB1 regulates the expression of nuclear receptor TR4. Biochem. Biophys. Res. Commun. 490: 423-428, 2017.
- Sato Y, Tsuyama T, Sato C, Karim MF, Yoshizawa T, Inoue M, Yamagata K. Hypoxia reduces HNF4α/MODY1 protein expression in pancreatic β-cells by activating AMP-activated protein kinase. J. Biol. Chem. 292: 8716-8728, 2017.
- Yamagata K, Karim MF, Sato Y, Yoshizawa T. Role of SIRT7 in hepatic lipid metabolism. Diabetology International 6: 193-196, 2015.
- Yoshizawa T, Karim MF, Sato Y, Senokuchi T, Miyata K, Fukuda T, Go C, Tasaki M, Uchimura K, Kadomatsu T, Tian Z, Smolka C, Sawa T, Takeya M, Tomizawa K, Ando Y, Araki E, Akaike T, Braun T, Oike Y, Bober E, Yamagata K. Sirt7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway. Cell Metabolism 19: 712-721, 2014.
- Ohki T, Utsu Y, Morita S, Karim MF, Sato Y, Yoshizawa T, Yamamura K, Yamada K, Kasayama S, Yamagata K. Low serum level of high-sensitivity C-reactive protein in a Japanese subject with MODY3. J. Diabetes Invest. 5: 513-516, 2014.
- Karim MF, Yoshizawa T, Sato Y, Sawa T, Tomizawa K, Akaike T, Yamagata K. Inhibition of H3K18 deacetylation of Sirt7 by Myb-binding protein 1a (Mybbp1a). Biochem. Biophys. Res. Commun.441: 157-163, 2013.
- Sato Y*, Hatta M*, Karim MF*, Sawa T, Wei FY, Sato S, Magnuson MA, Gonzalez FJ, Tomizawa K, Akaike T, Yoshizawa T, Yamagata K. Anks4b, a novel target of HNF4α protein, interacts with GRP78 protein and regulates endoplasmic reticulum stress-induced apoptosis in pancreatic β-cells. J. Biol. Chem. 287: 23236-23245, 2012 (*equal contribution).
- Yamagata K, Senukuchi T, Lu M, Takemoto M, Karim MF, Go C, Sato Y, Hatta M, Yoshizawa T, Araki E, Miyazaki J, Song WJ. Voltage-gated K+ channel KCNQ1 regulates insulin secretion in Min6 β-cell line. Biochem. Biophys. Res. Commun.407: 620-625, 2011.