Drawn

         To

             Science

Onovo  Pharma aims to deliver innovative, life-changing solutions that bring hope to many patients and their families. We are interested to develop and deliver new therapies to solve unmet medical needs and save lives.

Research and Development

A field of interest is to create and evaluate targeted molecular imaging agents (TMIAs) that detect cancers by using confocal fluorescent microscopy (CFM). Cancer is one of the main causes of deaths worldwide, accounting for 8.2 million deaths in 2012 (World Health Organization 2015). Tissues and organs are three dimensional so 3D cellular models provide a stronger understanding of how tumor grows than 2D culture. Cells that are grown in 2D tissue culture dishes differ significantly in their morphology than cells grown in 3D environment. Many studies have showed that cells can sense the chemical constitution of the extracellular matrix and its physical characteristics. In vitro three dimensional collagen matrices are used to mimic in vivo cellular environments to better understand cell migration, growth and survival. Different fluorescent dyes stain different biological structures.

Cancer cells growing in 2D culture dish stained with Nuc Blue and MitoTracker. Note the flattened morphology.Nuc Blue stains the nuclei in the cells and MitoTracker Red stains the mitochondria.

Cancer cells growing in 3D culture, stained with Nuc Blue and MitoTracker. Note the spheroid morphology. Nuc Blue stains the nuclei in the cells and MitoTracker Red stains the mitochondria.

Another area of interest is drug design using molecular docking programs to study proteins involved in cancer for the purpose of finding better inhibitors.The PI3K/ AKT/mTor pathway is one of the most important pathways related with different cancers. Faulty signaling in the PI3K/AKT pathway can lead to resistance to cancer therapies.This pathway is controlled by tyrosine kinases and regulates cell growth, proliferation and survival. AKT is a protein kinase b and it’s over phosphorylation can lead to uncontrolled cell growth. Phosphorylation is the most common biochemical modification that may alter the activity of a protein or regulate an enzyme by turning it on or off. AKT is activated when both serine and threonine residues are phosphorylated. Then active AKT phosphorylates many nuclear and cytosolic proteins like GSK3 beta that have crucial roles in cell survival and metabolism.Glycogen synthase kinase 3, beta plays an important role in the regulation of many cellular functions including growth, cell cycle progression, embryonic development and apoptosis.Therefore, inhibition of the over phosphorylation is essential in cancer therapies. Molecular docking programs are used to predict the position of ligands within the binding pocket of the protein before testing for potential drugs in vitro.

Graphical view of the interaction between the protein ( blue, green,red surface) and the ligand (green, blue and grey sticks). Yellow dashes display polar contacts between the protein and  ligand.

References

Osaki M., Oshimura M., Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis. 2004;9(6):667–676. doi: 10.1023/b:appt.0000045801.15585.dd.

Bardhi K, Bardhi K, Craig P, Bernstein H. Targeting AKT pathway in glioma by using bioinformatics tools. Rochester Institute of Technology.2015.

Yamada, K. M. & Cukierman, E. Modeling tissue morphogenesis and cancer in 3D. Cell 130, 601–10 (2007).

Bardhi K, Evans I.Utilizing 2-D, 3-D Collagen Cultures to Represent In Vivo Cancerous Tumors and to Test  Targeted Molecular Imaging Agents. Rochester Institute of Technology.2015.