The main focus of research in our laboratory is to understand the biochemical mechanism of oxidation-/inflammation-induced pathologies. Specifically, we have investigated the role of 4-hydroxynonenal (HNE), a toxic lipid peroxidation end-product, and one of its major detoxification enzyme, Aldehyde dehydrogenase1A1 (ALDH1A1) in various ocular and non-ocular pathologies. We have also been investigating the role of metals in such pathologies.
Current ongoing projects in the Ansari Laboratory:
1. Sarcopenia and Alcoholic Myopathy: Role of HNE and ALDH1A1
During aging and chronic alcohol exposure, excessive generation of toxic lipid aldehyde, HNE, accompanied by its compromised detoxification, causes damage to both muscle fibers and satellite cells (muscle stem cells). ALDH1A1, an important cytosolic enzyme, not only detoxifies HNE, but also imparts myogenic potential to the satellite cells. If HNE is not detoxified, it can form protein-HNE adducts, cause changes in membrane fluidity, and induce activation of caspases and consequent apoptosis. Alternatively, inflammatory signals can become activated, giving rise to more ROS and thus amplifying the signal in an autocrine/paracrine manner. The cytoskeletal proteins of the muscle fibers can readily form protein-HNE adducts that have serious consequences for muscle strength and function. Due to its involvement in cell differentiation, ALDH1A1 would participate in signaling the induction of myotube formation in the skeletal muscle. This project focuses to evaluate the role of HNE and significance of ALDH1A1 in satellite cell myogenesis during sarcopenia and chronic alcoholic myopathy.
2. Localized topical metal modulation to inhibit burn progression
The hypothesis is that the early down-regulation of inflammation via localized metal modulation soon after the occurrence of the injury will speed healing (and prevent the systemic effects that often occur post burn injury).However, chelating agents that are used in reducing metals are charged molecules, and do not cross membrane boundaries. This fact has largely prevented chelating agents from being used effectively to treat disease situations created by an over active inflammatory response (e.g. burn injuries.) Using its proprietary technology, Livionex has overcome this barrier to using chelating agents, and we have shown in-vitro and in-vivo that its methodology is very effective in down-regulating the inflammatory response. Using a brass- comb burn animal model (rat and porcine) in collaboration with Shriner Burns and Department of Anesthesiology, efficacy of the metal modulating lotion to inhibit the progression of full thickness burn is evaluated using imaging, histopathology, immunohistochemistry and biochemical/molecular biology techniques.