@ Rush University Medical Center, Chicago
Allosteric agonism as a novel strategy for targeting Integrins
Our research is focused on Integrins – a family of cell surface receptors that are essential for mammalian cell adhesion, migration and biological functions. Every cell in our body expresses at least one type of integrin receptor n its surface and these receptors often provide a “Cellular address” for the cell type. Thus, integrins are an important family of therapeutically target-able receptors. Given that one of the most well studied function of these receptors is ligand binding, many researchers have targeted integrins by identifying blockers of integrin ligand binding (“antagonists”) and developing them as potential therapeutics.
As an alternate strategy, we were among the first to propose targeting integrins in an exact opposite way – via allosteric agonists – as opposed to the antagonist – and were the first to develop allosteric agonist small molecules against one integrin (CD11b) into a therapeutic in the clinic. Over the years, we successfully developed novel allosteric agonists against multiple integrins and have shown that this mechanism is widely applicable to many members of the integrin family. Research in the laboratory is currently focused on developing such agonists against under-studied integrins and fully evaluate their mechanism as well as biological efficacy. This has opened up a completely novel approach for how this therapeutically important class of receptors can now be targeted with small molecules, antibodies and other agents, and several labs and companies around the world are pursuing it.
SeqStain – a simple and efficient approach for Spatialomics – multiplex tissue imaging
We recently developed a novel technique using DNA-tagged antibodies to study spatialomic profiles of biological cells and tissues. Our method is highly versatile, easy-to-use, and gentle to the samples that allows deeper insights into the spatial organization of various cell types in any tissue and an ability to generate spatial relationship maps (SRMs) between them.
Protecting podocytes from damage in Chronic Kidney Disease
Podocytes form the filtration barrier in the kidneys and their damage is a central hallmark of all chronic kidney diseases. Therefore, we recently developed a first-of-its-kind high content screening assay to identify compounds to protect podocytes from injury. Current studies in the laboratory are focused on understanding the molecular and cellular signaling mechanism of our novel hits as well as their efficacy in models of FSGS, diabetic kidney disease and alport’s syndrome.