Project: Assessing how the glucocorticoid receptor contributes to the effect(s) of dissociative steroidal compounds
Jesse Damsker, PhD
Glucocorticoids (GCs) are the standard of care for many inflammatory diseases including rheumatoid arthritis, asthma, and inflammatory bowel disease. While extremely effective, GCs are known to cause detrimental side effects such as weight gain, osteoporosis, type II diabetes, and hypertension. ReveraGen BioPharma has developed a class of dissociative steroidal compounds that have the potential to retain the beneficial anti-inflammatory effects of GCs yet lack the unwanted side-effects. The exact mechanism of action of these compounds remains to be elucidated. Thus, students will be assisting with the task of determining such mechanisms, including assessing how the glucocorticoid receptor contributes to the effect(s) of these compounds. In addition, students will play a role in carrying out testing of these compounds in preclinical models of inflammatory bowel disease and multiple sclerosis.
Project: Use of SILAC Preclinical Model to Study Duchenne Muscular Dystrophy and Response to Treatment
Yetrib Hathout, PhD
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscle disease, affecting one in 3,500 boys. The disease is due to a genetic defect leading to lack of expression of dystrophin, an essential protein in muscle. DMD Patients often become wheelchair-bound by age 10-12 years and die in early adulthood due to muscle wasting, cardiac and/or respiratory failure. Currently there is no cure for the disease. Treatment by corticosteroids delays muscle degeneration but does not stop disease progression. In the last couple of years new generations of drugs aiming to restore dystrophin expression have been introduced. The most promising one is a gene-based approach using antisense oligonucleotides. However, the duration of the treatment, and the toxicity and efficacy of these antisense drugs are not known. The goal of this project is to use a highly accurate and highly sensitive proteome-profiling method to monitor toxicity/efficacy ratio in a Duchennemurine model treated with different drug doses. First we will evaluate the proteomics method, then perform proteome profiling on tissue samples from treated and untreated murine samples. We will then conclude with the efficacy/toxicity ratio by examining dystrophin restoration in the muscle and signs of toxicity in the kidneys.