Robert White, PhD
Dean of the College of Biosciences, Professor of Molecular Biology and Medical Genetics
Research Interest: Development of Therapy for Duchenne Muscular Dystrophy (DMD)
My lab has been developing a novel therapy to treat DMD, a lethal muscle degeneration disease commonly found in boys for which there is no cure and is caused by the lack of a muscle protein called dystrophin. Expression of a protein from the eye (retinal dystrophin) in DMD model mice by a transgene cures the mice of their disease which includes severe muscle degeneration accompanied by loss of limb movement and early death. Our next goal is to move from the lab bench to the bedside of patients. We are identifying the promoter of the retinal dystrophin as a first step in identifying drugs which will induce its expression in muscle. The genetic machinery to make eye dystrophin in muscle in present in many DMD patients but is not used because it is not retinal tissue. Our long range goal is to find drug(s) that induce expression of eye dystrophin from its promoter in muscle as a cure for DMD.
Hematological Diseases – two projects
(1) Iron overloading is a debilitating disease which can occur in a genetic disease (Hereditary Hemochromatosis) or in blood transfusion-dependent diseases such as beta-thalassemia and sickle cell disease. Iron overloading can lead to heart, kidney and pancreatic disease which presents as severe morbidity. The treatment for this disease is using iron-chelating drugs for which patient compliance is low. Hemochromatosis patients are treated by bloodletting as this is the only method by which treatment can remove iron from the body. Our lab has a mouse mutant that excretes 100X more iron in urine and, when mated to hemochromatosis model mice, can prevent iron overloading. Our study is to identify the mechanism and pharmaceutical targets to induce this urinary iron excretion to treat patients with iron overload.
(2) In a second project, the lab is in the process of identifying a novel erythroid transcription factor to treat anemia and potentially identify a novel treatment for leukemia. This work derives from the study an interesting mouse mutant (call Xpna: x-linked pre and neonatal anemia) which lacks the most important erythroid transcription factor called GATA1. The mice with a GATA1 mutation are born anemia but unexpectedly receiver from their anemia. The hypothesis being tested is that there is a compensatory erythroid transcription factor that replaces GATA1 in these mice and also has the likely characteristic that it can prevent leukemia as well.