Accidental (environmental or occupational) and self-inflicted (suicide) exposure to organophosphate (OP) pesticides is encountered frequently in the eme rgency room, especially in the developing world. These perennial public health i ssues are compounded by a growing concern over the potential use of OP nerve age nts such as sarin as a means of terror and nonconventional warfare. OPs disrupt neurotransmission by inhibiting synaptic acetylcholinesterase (AChE-S), leading to the accumulation of acetylcholine in the synapse and neural over-stimulation. The severity of the ensuing nicotinic and muscarinic symptoms is dose-dependent and can result in death due to cardiovascular and respiratory collapse. Those s urviving the initial insult often suffer long-term sequelae, including OP-induce d delayed neuropathy, muscle weakness, permanent brain dismorphology and social/ behavioral deficits.
Existing medical practices address the short-term, but not the delayed co nsequences of OP intoxication. Bioscavenging of organophosphate (OP) by human pr oteins is emerging as a promising alternative medical intervention for prophylax is and post-exposure treatment against chemical warfare nerve agents. The best-s tudied bioscavengers (BSCs) to date, meeting considerable success in pre-clinica l research, are human cholinesterases (ChEs). However, ChEs, which are highly ef ficient in binding and sequestering OPs, are also inactivated by the toxins and therefore operate as stoichiometric rather than catalytic BSCs. This necessitate s the availability of large quantities of enzymes. In the near term, outdated hu man plasma can be a first generation source of one such enzyme, butyrylcholinest erase (BChE), that may be used in clinical trials to validate its safety and eff ectiveness in biodefense. In the longer term, development of a new generation of BSCs that can catalytically degrade OPs is needed, while a cost-effective and s ustainable alternative source of BSCs must be identified to establish and mainta in a strategic reserve.
Containment of the HIV/AIDS pandemics depends on our ability to minimize and possibly prevent transmission of the virus. Despite the success of extensive AIDS prevention programs and powerful anti-retroviral drugs in limiting the spread of HIV in high-income countries, it is generally agreed that these efforts will have to be combined with effective prophylaxis through vaccination and the use of microbicides. These preventative efforts are even more crucial for low-income and impoverished countries, where more than 95% of people living with HIV/AIDS reside. An important consideration is that the effective vaccine should also be inexpensive to allow for its wide-spread use.
In the Mor lab, we are using protein engineering for the construction of a promising vaccine-candidate consisting of a mucosal targeting component fused to a peptide corresponding to a portion of the HIV-1 envelope protein gp41, a region which is not only the target of two broad-spectrum neutralizing monoclonal antibodies, 2F5 and 4E10, but was also shown to be critical for the mucosal transmission of the virus. Systemic and mucosal antibodies raised in pre-clinical experiments against this novel immunogen were shown by us to be able to inhibit the crossing of a tight epithelial cell layer by an HIV-1 primary isolate, and were also promising in their ability to neutralize infection of CD4+ cells. The immunogen, as well as “next generation” candidates, are expressed in a variety of systems including bacteria, insect cells and plants.
Intel Corporation $2.3 million equipment donation advances ASU medical research and student learning
A donation of equipment from the Intel Corporation to Arizona State University will put sophisticated technology to an entirely new use that could result in earlier, less costly diagnosis of disease. A long-standing supporter of ASU research and programs, Intel donated equipment, which has a market value of more than $2.3 million. The majority of the equipment will be used by ASU’s Biodesign Institute on promising research that aims to detect illness before there are any symptoms of the disease.