Our research involves the application of gene engineering, biochemical and biophysical experiments aimed at elucidating the relationship between the structure and biological function of oligomeric proteins. Much of our work is focused on the ATP synthase enzymes from mitochondria, chloroplasts, and bacterial cytoplasmic membranes, as well as a family of transcription factors which utilize a structure similar to that of the ATP synthase to regulate procaryotic transcription.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting multiple organ systems and characterized by the production of a wide variety of autoantibodies. A multitude of environmental, genetic, hormonal, and immunoregulatory factors participate in the etiology and pathogenesis of the condition. Current therapy involves the use of general immunosuppressive agents such as prednisone and azathiaprine, which are inadequate and accompanied by serious side-effects and/or toxicities. The laboratory is investigating the possibility of using recombinantly prepared ricin A chain fused to SLE autoantigens to specifically target, and kill, only the immature B lymphocytes that will produce the corresponding autoantibodies.

The Suprenant lab investigates how the cytoskeleton affects cell signaling and cell structure/function in muscles and sensory neurons of the nematode Caenorhabditis elegans.

Research in my group focuses on the structure-function relationships of the key proteins that are involved in various biological processes. Three-dimensional structures of enzymes (proteins) have been determined at atomic resolution by a single crystal X-ray diffraction method. On the basis of the structures and site-directed mutagenesis studies, catalytic mechanisms of enzymes have been elucidated. Small inhibitor molecules have been designed, synthesized, and tested. Currently, we have focused on the structures and functions of proteins involved in prostanoid metabolism in humans. Most of these proteins are membrane proteins.

Many biological processes are carried out by complex, multi-component macromolecular assemblies. The assembly and dynamics of these molecular machines has been central to structural and cell biology, and has imposed tremendous challenges owing to their unusual complexity. The research in this lab aims to understand the structural basis of assembly, dynamics and function of molecular complexes by using X-ray crystallography and electron cryo-microscopy as primary techniques. The current research is focused on viruses and bacterial infectosome.

Double-stranded RNA (dsRNA) elicits significant biological effects in many different species, including humans. These effects include systemic responses that prevent establishment of a foreign genome—defenses against viral or transposon invasion, for example. dsRNA can also lead to sequence-specific gene silencing in many plants and animals, a process referred to as RNAi in Caenorhabditis elegans or post-transcriptional gene silencing (PTGS) in other species. These effects are dependent upon entry of dsRNA into cells—dsRNA has an intrinsic ability to enter cells and spread throughout an organism. Our lab is investigating the mechanisms that mediate dsRNA cellular uptake and spreading using genetic, molecular, and cellular approaches in the model organism Caenorhabditis elegans.

The research in our laboratory focuses on molecular modeling in the context of structural genomics and bioinformatics. The major goals are to develop approaches to the modeling of protein interactions and to design procedures for reconstruction of the network of connections between proteins in a genome.

The primary interest of my lab is understanding the mechanisms that provide spatial and temporal specificity for morphogenesis. We study the elongation and eversion of the adult legs in Drosophila because of the relative simplicity of this system and the availability of powerful molecular and genetic tools. Leg morphogenesis is triggered by a steroid hormone and requires signaling through the Rho1 small GTPase. Our current efforts are aimed at understanding how hormonal signaling regulates Rho activity in the cell.

Molecular therapy targeting cancer and cancer stem cells: Funded by NIH and DOD, my lab is working on molecular targeted cancer therapy and chemo/radiosensitization by modulating cell death signaling pathways. We are exploring microRNAs as novel targets/therapeutics for cancer and cancer stem cells. We are currently using novel nanotechnology to develop nanovectors targeting cancer cells for siRNA/miRNA-based novel cancer therapeutics. We are also developing nanovectors targeting cancer stem cells and exploring novel molecular therapy for cancer stem cells.