About OUR RESEARCH
Molecular Diagnosis of Hypercortisolism (Cushing's Syndrome)
Cushing Syndrome, also known as hypercortisolism, is a condition characterized by abnormally high concentrations of the stress hormone cortisol in the blood. Diagnosis of hypercortisolism is both difficult and time-consuming, taking up to 6 months of tests. The enzyme 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) is responsible for the interconversion of inactive cortisone to cortisol. Using Reverse Transcriptase Quantitative Polymerase Chain Reaction (RT-qPCR), a protocol was developed to quantify the expression levels of HSD1 in an effort to establish a correlation with cortisol levels.
Quantitative Distance Determination
Specifically, we are interested in the advancement of subjective forensic examinations by developing more objective methods using modern instrumentation. The current method employed for distance determination in firearms analysis is antiquated and depends on subjective visual evaluation of colorimetric tests that respond to inorganic components of gunshot residue (GSR). Thus, we are developing evidence extraction methods, along with chromatographic and spectroscopic methods for the analysis of both organic and inorganic components of GSR for the purpose of determining the distance a firearm was from the victim when discharged.
Molecular Cloning of STRs
In the Forensic DNA discipline, Short Tandem Repeat (STR) analysis is the ‘Gold Standard’ for individualization. We are using routine molecular biology methods to reproduce a human STR profile in molecularly cloned bacteria to demonstrate the unreliability of STR analysis in individualization. We are also developing Real-Time PCR methods to distinguish between the identical STR profiles of a human and a cloned bacterium.
Computational Investigation of Novel Antibiotics
With rising antibiotic resistance and the development of novel antibiotics a low priority, in collaboration with the Pelphrey Lab, a computational investigation of novel antibacterial drug candidates based on a 1,2,4 oxadiazole linker was performed to evaluate their potential as inhibitors for bacterial Dihydrofolate reductase (DHFR), an important enzyme involved in DNA and RNA synthesis. Density functional theory with the Becke-Style three parameter Lee-Yang-Parr correlation functional (B3LYP) and the 6-311+g(d,p) basis set was used to obtain the geometry optimizations, frequency calculations, and Gibbs Free Energy for each candidate molecule. Electrostatic Potential (ESP) maps were then calculated and constructed for comparison with methotrexate, a DHFR inhibitor that binds 1000x stronger than its natural substrate.
Enzymatic Investigation of Novel Antibiotics
Also, in collaboration with the Pelphrey Lab, we are heterologously expressing dihydrofolate reductase (DHFR) enzymes from multiple bacterial species for use in enzyme kinetics and inhibition studies with novel diaminopyrimidine-based antibiotic candidates with oxadiazole and triazole linkers.