My research interests are in the general area of iron-protein biochemistry and part of a major international effort to understand the role of iron in health and disease. The goal is to elucidate structure-function relationships of different iron-binding, iron-transport, and iron-storage proteins and better understand their roles in the regulation of cellular iron homeostasis. Our hope is to generate new knowledge that is essential for the rational development of new treatments for iron overload diseases and other defects in iron metabolism.
The importance of this research stems from the fact that iron is an element where you “Can’t live without it but you can’t live with too much of it”. Excess free iron has been implicated in neurodegenerative diseases, apoptosis (or cell death), and in the generation of harmful free radicals that cause damage to membranes, proteins and nucleic acids. The low solubility of iron at physiological conditions (~ 10-18 M) has compelled living organisms to adapt efficient iron transport and storage mechanisms. Of interest to our research program are two major iron-proteins including transferrin, a plasma iron transport protein, and ferritin, a ubiquitous and multi-subunit iron storage protein, both of which playing central roles in minimizing iron toxicity and controlling intracellular iron homeostasis. The two proteins have been used as nanotemplates in nanochemistry, nanobiology, and nanomedicine and have been the subject of intense investigation particularly because the uptake, storage, and release of iron are key cellular processes occurring during the normal course of iron metabolism. Current research efforts in our laboratory, supported by several grant agencies, including the National Institute of Health (NIH), the National Science Foundation (NSF), Research Corporation for the Advancement of Sciences, Dreyfus Foundation, and others (please see Grants and Awards), are aimed at understanding the effect of ferritin H and L subunit composition on iron core formation, morphology, iron mobilization and the physiological relevance of these processes. We believe that our research will provide fundamental insights into the role of the ferritin shell in controlling the morphology of the iron mineral and the biochemical processes responsible for iron-related disorders, such as Alzheimer, Parkinson, beta-thalassemia, hemochromatosis, and neuroferritinopathy. We collaborate with several national and international research groups including Profs, Paolo Arosio and Sonia Levi in Italy, Prof. Artem Melman at Clarkson University, NY, Prof. Georgia Papaefthymiou at Villanova University and Prof. Eric Stach at UPENN, among a few others.
Another important research project involves investigating the molecular basis of malaria and age-related macular degeneration. The World Health Organization estimated that malaria accounts for more than 200 million clinical cases worldwide and more than half-a-million deaths, mostly of children in sub-Saharan Africa. Although the disease is both preventable and curable, undesirable side effects from common drugs may lead to serious diseases. On the other hand, age related macular degeneration is the leading cause of blindness in individuals over 50 and is believed to be caused by a buildup of lipofuscin (yellow pigment granules formed as byproducts of lysosomal digestion), with A2E (a vitamin A-based bisretinoid) being a major component of that pigment. Our efforts in this area of research aim at investigating (A) the molecular mechanisms of two of the most prescribed anti-malaria drugs, Chloroquine and Atovaquone, and their interaction with a human lysosomal protein called saposin B (SapB), and (B) the role of SapB in binding A2E and in preventing age-related macular degeneration. To this end, we collaborate with Prof. Robert Doyle at Syracuse University, and Prof. Chloe Zubieta at the University of Grenoble, France.
Our research is supported by several federal agencies and private foundations resulting in over 1.5 million dollars in research funding (see Grants and Awards) and over 50 peer-reviewed publications (see Publications).
Interested students should contact Dr. Bou-Abdallah at firstname.lastname@example.org
Last Updated: 7/3/2021