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Research Interests

 
  • A small animal model for Hepatitis B and C virus (HBV & HCV) infections
  • Human monoclonal anti HBV and HCV antibodies that underwent a clinical translation
  • Understanding the role of IL6 and IL6 trans-signalling in tissue regeneration
  • A siRNA based therapy against pancreatic cancer – currently in phase II clinical studies
  • Found the mechanism of inflammation induced anemia – miR122 dependent
  • Identified the role of miR122* in HCC development
  • Mechanism of radiation induced alopecia, and found a therapy for this
  • Mechanism of the “killer” of the horn of Africa, Nodding syndrome: An autoimmune malady
  • Role of microRNAs in the development of non-alcoholic steatohepatitis
  • Role of IL6 in radiation induced senescence and xerostomia
  • Mechanism of HCC development following radio-frequency ablation
  • Role of the lncRNA H19 in HCC development
  • Developed the oncolytic virus, Newcastle Disease virus for treating Glioblastoma multiforme
  • Developed femtosecond ultrafast infrared laser for gene transduction
  • Currently developing new drugs for NASH based on our findings of miR-122 in triglyceride metabolism.

 

Both hepatocytes derived microRNA-122 and microRNA-122*, as others and we show have a tumor suppressive effects. This figure adopted from an editorial (Hepatology. 2016 Nov;64(5):1424-1426) on our report summarizes the known about microRNA 122/122* biogenesis and targets through which tumor suppression is mediated
 
Figure 2: Upon inflammation TNFα induces microRNA-122 expression and secretion. This microRNA then circulates in the blood stream to reach the cells in the kidney which produce erythropoietin. This microRNA-122 targets the seed sequence of the message of erythropoietin to reduce its expression.
 
Figure 3: Free fatty acids via RORα induce the expression of microRNA-122. This increase then is followed by microRNA-122 effect inside the liver for the reduction of triglycerides biosynthesis by targeting the 3’-UTRs of two mRNAs of genes involved in triglycerides biosynthesis. The microRNA-122 then is secreted out of hepatocytes to target peripheral cells including adipocytes, muscle cells and heart muscle cells. In these cells, there is also a reduction of triglyceride biosynthesis, and increase in free fatty acids which then reach the liver and hepatocytes through the circulation and complete this “hormonal” type of circle, by inducing moicroRNA-122 increase.
 
Figure 4: Our team is interested to identify the cell of origin of liver cancer, the hepatocellular cancer. To do this we have engineered a number of mouse models and are now following them. We have found that there is evidence for the origin of a specific type of cancer in the liver that originates from the putative liver stem cell. We are now further investigating this and developing therapeutic approaches.
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