Artemisinin combination therapy (ACT) is the main treatment for Plasmodium falciparum malaria: the success of this treatment has rolled back malaria and renewed interest in malaria elimination. Slow clearance of parasites following ACT treatment of patients in SE Asia has lead to concern about the spread of resistance. This proposal aims to identify the genes that underlie slow clearance to better understand the evolution and biochemical basis of his trait.

Schistosomes are the most important of the helminth parasites that infect humans. Larval stages infect aquatic snails, so the transmission cycle can be broken by interfering with this stage in the parasite lifecycle. We will use genetic crosses of schistosomes in the laboratory to identify the parasite genes that underlie recognition of snail vectors and development of parasites within host snails.

The goal of this clinical research study is to learn the most effective way to give patients a vaccine in order for the immune system to react against folate binding protein (FBP) and FBP-containing cancers. The E39 and J65 peptide (a piece of a protein) vaccines are designed to cause the immune system to attack certain cancer cells (those with FBP), which may help lower the risk that the cancer will come back.

Bacterial infection is a frequent complication among trauma and surgical patients, both civilian and military.  The rate of infectious complications in the U. S. military is approximately 35 percent for combat casualties.  The lack of a rapid diagnostic platform for the detection of bacterial and fungal infections in combat wounds result in mortality and extended stays in Intensive Care Units. The methods currently available are time consuming, lack sensitivity, require specialized equipment, and highly trained personnel.

Project Summary. We have shown that regulatory T cells (Tregs) defeat anti-cancer immunity and that their depletion can be therapeutic, but their rapid regeneration is problematic. This project uses our discoveries that B7-H1 immune co-signaling facilitates Treg generation and that estrogen receptor (ER)? signals inhibit Treg regeneration in relevant pre-clinical mouse models with proven substantial translational relevance.

Myelodysplastic syndrome (MDS) is a group of disorders characterized by dysfunctional blood cells that can progress to acute myeloid leukemia (AML). At this time the etiology of MDS development and progression to AML is not understood and there is no cure (median survival at time of diagnosis is less than 5 years). Yet, DNA damage and mutations appear to play a key role with the initiating defect in a hematopoietic stem cell (HSC). In support, people with certain DNA repair defective syndromes including Fanconi anemia (FA) and Bloom syndrome (BS) exhibit MDS.

Subjects with impaired fasting glucose have increased risk of progression to T2DM. The metabolic defects responsible for the increase in FPG within the nondiabetic range have been poorly studied. A clearer understanding of the mechanisms of these defects will help to develop improved strategies to treat and prevent T2DM. We previously have shown that basal glucose clearance is decreased in IFG subjects.