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 this trait.

Therapeutics are scarce for several important viral groups and the situation is further confounded by the ability of viruses to rapidly mutate and evolve resistance to drugs. Filoviruses, such as Marburg and Ebola virus, are no exception to this. Researchers have shown viral mutations that lead to the virus being able to evade detection by neutralizing antibodies and evade host immunity. Dr. Hayhurst’s approach is to target an internal antigen, which is a molecule not under selective pressure to evolve thereby making a resistant proof therapeutic.

There is currently no cure for HIV and vaccine development has proved challenging. Patients are able to manage their disease with the use of highly active antiretroviral therapy (HAART), which has had a positive impact on reducing HIV morbidity and mortality. As with HIV infection in humans, infection with Simian Immunodeficiency Virus (SIV) in rhesus macaques is lifelong due to infected cells that lie dormant in the DNA of the virus that is integrated into the host DNA.

Chronic liver disease is the fifth leading cause of mortality in American Indian (AI) and Alaska Native populations. There are currently no data available on the development of fatty liver disease (steatosis) and fibrosis, early manifestations of chronic liver disease, in AI. Metabolic disease and alcohol are each associated with fatty liver disease, but their relative impact on its presence and severity are unknown.

The Role of Follistatin 1 Protein in Coronary Artery Aneurysms of Kawasaki Disease

The majority of host genetic determinants of HIV viral control identified in genome-wide association studies are in the non-coding regions and the functional mechanisms mediating these associations are still unknown. We are investigating functional impact of these non-coding RNAs on HIV viral control. Outcomes from the study outlined in this proposal will likely provide new therapeutic targets that can be manipulated in order to control HIV infection.

Treatment with a monotherapy (praziquantel (PZQ)) is the basis for control of parasite flukes in the genus Schistosoma, but imposes strong selection for resistance in the parasite population. This project will identify genes underlying PZQ resistance in parasites selected in the laboratory and in parasites that survive PZQ treatment in patients in order to (i) provide genetic markers for monitoring resistance evolution in the treatment programs and (ii) better understand the mode of action and mechanism of resistance.

The goals of this program are: Project 1) Biology of the human lung mucosa in aging and tuberculosis; Project 2) Biology of alveolar macrophages in aging and tuberculosis; Project 3) Defining age-associated immune correlates of susceptibility to M. tuberculosis; and Project 4) Defining immune correlates of susceptibility to M. tuberculosis infection in the elderly" Txbiomed Project: 4696

The purpose of this project is to design the scientific approaches, collect the appropriate molecular genetic data, develop manuscripts of the results generated from this study and conduct the administrative activities needed for its successful completion of genotyping up to 960 single nucleotide variants (SNV) in candidate genes affecting type 2 diabetes and chronic kidney disease in up to 460 Strong Heart participants’ DNA samples.