Molecular Imaging with MRI
A goal of the Meade lab is the development of magnetic resonance imaging (MRI) probes capable of reporting on anatomical and physiological function of cellular processes in whole animals. MRI has proven to be an effective modality for molecular imaging applications by providing excellent spatial and temporal resolution and unlimited depth of penetration without the use of ionizing radiation. The bioactivated Gd(III) complexes prepared in this research are designed to report on a biological event of interest and transduce this metabolic signal and/or cellular status as a change in MR contrast. Additionally, targeted Gd(III) probes are being prepared to report cellular status through signal enhancement as a function of receptor expression. Our lab addresses the inherent sensitivity issues associated with MRI by developing probes that increase cellular uptake, thereby maximizing Gd(III) loading using both molecular and nano-based approaches. Development of new MR probes addresses an unmet need for monitoring specific tissue types and environments relevant to dynamic biological processes.
Our approach begins with computation and synthesis and proceeds to biological assays, in vivo imaging and processing.
Transcription Factor Inhibition
The Meade lab seeks to understand and utilize Co(III)-Schiff base complexes (Co(III)-sb) as research tools and potential therapeutics. The complexes we study consist of a Co(III) center coordinated to an acetylacetonatoethylenediamine (acacen) backbone. The backbone can be modified to contain a targeting group, and axial ligand exchange dynamics can be exploited for biological or chemical utility.
Co(III)-sb complexes have been shown to irreversibly inhibit the activity of histidine-containing proteins by binding to histidine residues in the active site. Zinc finger transcription factors often contain a Cys2His2 type zinc finger that can be inhibited by Co(III)-sb. Co(III)-sb displaces Zn(II) and disrupts protein structure. For targeting, Co(III)-sb is tethered to the DNA consensus sequence of a specific transcription factor (making Co(III)-DNA). By inhibiting the activity of transcription factor proteins, gene transcription can be regulated. This can be exploited for use in cancer, developmental, and disease biology.