Dr. Giridhar R. Akkaraju
HCV PATHOGENESIS HCV is a very successful pathogen infecting over 170 million people worldwide. Chronic HCV infection is established in over 85% of cases, and approximately 70% of these individuals develop cirrhosis or hepatocellular carcinoma. There is currently no vaccine and the emergence of drug resistant strains is a major problem. Understanding how HCV evades the antiviral response will contribute towards the development of improved treatment strategies. This is the focus of one of the research projects in my laboratory. One of the tools HCV uses against the cell is a virally encoded signal transduction modulator protein NS5A, which binds to several proteins including dsRNA-dependent protein kinase (PKR) and inhibits its activation. This prevents the expression of cytokines like Interferon-beta (IFN-beta), which is required to induce the antiviral state in the infected cell. This allows the virus to persist in the infected cells of the liver. We are interested in understanding the mechanism by which NS5A inhibits expression of IFN-beta. We are also engaged in the identification of drugs that can inhibit NS5A. To do this we are using the promoter of the IFN-beta gene linked to the coding sequence of the enhanced green fluorescence protein (eGFP) gene. We are using the expression of eGFP following viral infection to test plant extracts for inhibitory activity against NS5A.
CANCER DRUG DEVELOPMENT Targeted therapy of cancer attempts to directly attack the defect in the cancer cell. Traditional cancer therapies using radiation and chemotherapy kill all rapidly dividing cells in the body leading to severe side effects. We are working on testing a new molecule containing a DNA-methylating agent conjugated to a steroid hormone. Binding of the hormone to its receptor leads to its transport to the nucleus where the receptor binds to the DNA. This brings the DNA-methylating agent in close proximity to the DNA where it can modify adenine residues and induce cell death. In effect, the steroid hormone acts as a “Trojan horse” and delivers a deadly cargo to the target cells. Since many steriod-dependent cancer overexpress the hormone receptors (e.g., estrogen receptor expressing breast cancer cells) this increases the specificity of the drug and reduces the side effects.
TISSUE ENGINEERING In collaboration with Dr. Jeffrey Coffer of the TCU Chemistry Department, we are testing a modified form of silicon (Porous Silicon-PSi) for use in a variety of applications. PSi is biocompatible and capable of a versatile range of surface modifications that can modify its properties, including its solubility and its affinity for payload molecules. Currently, we are trying to use these surface-modified Silicon microparticles for gene delivery to target cells.
I coordinate and teach the sophomore level Cell, Molecular and Developmental Biology course (BIOL 30603). At the junior and senior levels I teach a Writing emphasis course on Virology (BIOL 40603) and a laboratory course on the Molecular Biology of the Eukaryotes (BIOL 40133). I also teach an honors seminar on The Biology of Cancer (Biol 40001).
Virology (BIOL 40603) Writing Emphasis
Biology of Cancer (BIOL 40001) Honors Seminar
Cell, Molecular and Developmental Biology (BIOL 30603)
Molecular Biology of the Eukaryotes (BIOL 40133) Lecture and Laboratory