Dr. Oleinikov's Research
During his tenure in science, Dr. Andrew Oleinikov has worked in several fields of life sciences including protein biochemistry, infectious diseases, immunology and autoimmunity, vaccine development, molecular and cell biology, high-throughput approaches, and nanobiotechnology.
His earlier work was focused on the process of polypeptide chain elongation during protein biosynthesis on ribosome and structure-function relationship of ribosomal protein L7/L12. The main contribution was the determination of how different domains of the L7/L12 molecule interact with other proteins on the ribosome and with elongation factors, the importance of the flexible hinge for protein activity, and demonstration that C-terminal domains work independently and a single-headed dimer of L7/L12 is fully functionally active.
Later, Dr. Oleinikov also identified the first intracellular ligand of megalin, adaptor protein Disabled 2 (Dab2). This work led him to hypothesis that megalin, which was known as a giant endocytic receptor belonging to the LDL-receptor superfamily, might be involved in signal transduction through Dab2 as well as that Dab2 might serve as an adaptor protein for endocytosis of multiple cargo molecules. These hypotheses have been confirmed in a multitude of works and opened up a new avenue for studies of this endocytic/signal transduction system in a number of various organs and in embryonic development.
Before moving into the malaria field, Dr. Oleinikov developed a number of novel technologies based on an addressable array of electrodes on semiconductor microchips for: a) protein microarray manufacturing using in vitro and in situ protein biosynthesis; b) long gene synthesis; c) and electrochemical detection of protein-ligand interactions. This work resulted in four issued patents.
For the last 14 years his research has advanced knowledge of various aspects of malaria including the identification of vaccine candidates in childhood and placental malaria, with the main focus on the structure and function of P. falciparum adhesins, PfEMP1 family of proteins linked to sequestration of P. falciparum-infected erythrocytes in microvasculature/placenta and severe forms of malaria. The main contribution was the development and application of a quantitative functional protein microarray platform for high throughput screening of receptors and antibodies binding to a large family of PfEMP1 malarial surface proteins. This work resulted in identification of a novel ICAM-1-binding PfEMP1 domain and relating the immune response to this domain to protection against severe malaria and in development of a two-step system identification of anti-adhesion compounds that prevent sequestration of infected erythrocytes to the host receptors. This will lead to new adjunct therapy against severe malaria. At the intersection of his previous work (see above) on receptor megalin and on malaria, Dr. Oleinikov identified an important role for this receptor in the pathogenesis of malaria during pregnancy, which may provide a better understanding of pathology and new ways of treatment for this devastating disease.
Dr. Oleinikov’s research has been continuously funded by various divisions of the National Institutes of Health, and by the Bill and Melinda Gates Foundation.