In 2015, it was estimated that over 30 million people in the United States had diabetes with 1.5 million newly diagnosed cases every year. Diabetes remains the 7th leading cause of death in the United States. Diabetes is now recognized as a chronic inflammatory systemic disease and is associated with many health problems involving multiple organ systems. In recent years, a type of white blood cell called monocytes and their counterparts in tissues (called macrophages) have become increasingly implicated in the disease process. Diabetes induces an increased expression of colony-stimulating factor (CSF1), a substance that stimulates the production of blood cells and its receptor (CSF1R) in tissues. In this project, we are using a NHP model to evaluate the effects of inhibiting CSF1R in tissues on metabolic profiles. We believe that by targeting cells that express high levels of CSF1R we can stimulate the body to replace these with healthy cells. If effective, selectively targeting the high CSF1R expressing cells that contribute to the progression of diabetes could be used to prevent diabetes and diabetic complications.

More than 30 million people are infected with human immunodeficiency virus (HIV) worldwide, making HIV-AIDS (acquired immunodeficiency syndrome) a global health problem. The number of HIV-infected patients continues to increase despite decades of prevention efforts using traditional vaccine strategies. Although antiretroviral therapy (ART) improves survival and quality of life of HIV infected individuals, it fails to cure infection. While ART reduces the amount of virus circulating in the bloodstream, often to undetectable levels, HIV “hides” in tissues (known as “reservoirs”) throughout the body and rebounds to high levels as soon as treatment is interrupted. The perivascular macrophage (PVM) is an immune cell in the central nervous system (CNS) and is the target of HIV during acute infection. These cells have been found to contain virus even when ART suppresses viral load in the blood below the level of detection. In this study we are a NHP model to evaluate whether infected cells can leave the CNS and infect other parts of the body, and to test a treatment that targets those infected cells. These studies have the potential to control HIV infection and eliminate the need for life-long ART drug treatment.

Human Immunodeficiency virus (HIV) is a virus that attacks the immune system which is the body’s natural defense system. HIV attacks a specific type of white blood cell called CD4 T cells, which are important for fighting off infections. When HIV enters the body, it starts to replicate inside CD4 T cells, which eventually destroys these cells. Over time, the immune system becomes weaker and less able to fight off infections, which can result in a condition called acquired immunodeficiency syndrome (AIDS). HIV reservoirs are like hiding places where the virus can "hide" in the body even when someone is receiving treatment for HIV. Antiretroviral therapy (ART) is a medication used to treat HIV, and it can effectively suppress the virus and prevent it from replicating in most parts of the body. However, there are certain places in the body, known as HIV reservoirs, where the virus can continue to persist even with ART. HIV reservoirs are typically found in cells and tissues that are not easily accessible to ART, such as in the brain, lymph nodes, and gastrointestinal tract. The virus can lie dormant in these reservoirs for a long time, and if ART medication is stopped, the virus can start replicating again and cause HIV to rebound. The presence of HIV reservoirs makes it challenging to cure HIV completely. Although ART can effectively control the virus and allow people living with HIV to lead healthy lives, it cannot eliminate the virus from these reservoirs. In this study, we are using a NHP model by using a combination of investigative compounds for the clearance of the viral reservoir in a nonhuman primate model of ART-treated HIV infection. This combination of experimental compounds allows for selectively killing cells producing simian immunodeficiency virus (SIV).

People with HIV can achieve undetectable levels of the virus in their blood through antiretroviral therapy (ART). This means that the virus is present at such low levels that it cannot be detected by standard tests and cannot be transmitted to others. However, if people stop taking ART, the virus can quickly rebound to high levels. One reason for this is that HIV can hide in certain types of cells and tissues, such as macrophages (a type of white blood cell) and the brain. This is called the viral reservoir. In this study, we are using a NHP model, infected with SIV (a virus similar to HIV) to confirm that long-lived macrophages in tissues, especially the brain, are a major part of the viral reservoir. The researchers will also test a treatment to remove these infected cells, with the goal of eradicating the virus from the body altogether.