Transitioning Investigator Awards Recipients

This research project focuses on studying two new ways to help wake up the hidden HIV virus in the body. The HIV virus can hide in certain cells in a "sleeping" or latent state, making it difficult to eliminate the disease completely with current treatments. When the virus is latent, it doesn't cause harm and can't be attacked by the immune system or medications. Novel ways to wake up the hidden virus so that it can be targeted and destroyed, must be made to lead to a complete cure for HIV/AIDS. 

The project has two main goals: 

1. Study how a gene called CYLD helps wake up the latent HIV virus. The researchers believe that when CYLD is changed, it starts a chain reaction in cells that leads to the virus waking up. The team will conduct experiments to see if their hypothesis is right, and also try to find new drugs that can help make this happen. 
2. Study how another gene, YPEL5, helps wake up the latent HIV virus. The researchers believe that when YPEL5 is changed, it stops breaking down an important protein needed for the virus to wake up. Experiments will be ran to find out which protein is involved.

The research team led by Dr. Wei Li, has a lot of experience in studying genes and how they work. In addition, Dr. Li is an expert in using deep learning and gene editing technologies to find new drug targets. They hope that our project will help bring together other scientists working on HIV/AIDS, and lead to new ideas for finding a cure. 

Non-alcoholic fatty liver disease (NAFLD) is caused by excess accumulation of fat in the liver. Importantly, NAFLD can lead to other diseases such as diabetes, cardiovascular disease and even liver cancer. People living with HIV are at an extremely high risk for developing NAFLD.

However, the reasons why HIV causes fatty liver remain unclear. The brain is important for controlling the liver. In a mouse model, Dr. Young and his team are testing the hypothesis that HIV leads to changes in the brain that alter its communication with the liver and cause NAFLD.

Overall, this project will provide knowledge into a disease that affects many people living with HIV. The findings will be shared with the public in the form of papers and presentations to help those living with HIV understand why they may develop NAFLD.

HIV infection of the brain can cause problems with cognitive functions like decision making and memory, as well as problems with movement. Some degree of these problems are seen in approximately 40% of individuals living with HIV. These problems are worse when HIV infection occurs early in life, for example, when the virus is transmitted from mother to child. One way that we can understand how HIV causes these problems after exposure in infancy is to use an animal model.

Here, the researchers propose to use a rare and valuable resource, brains collected from monkeys that were exposed to virus early in life. These brains have already been collected as part of a study developing vaccines for HIV. This will provide a unique opportunity to use this precious resource to advance our knowledge of HIV effects on the developing brain. They will perform MRIs on these brains to determine how virus infection altered brain structure. Through these experiments, they will determine how different strains of virus impact the brain, and also determine how medications used to treat HIV might protect against this brain damage. By examining these brains, the researchers aim to generate a model that would allow us to test new therapies to minimize the impact of HIV on the developing brain. This builds on the existing strengths in HIV research in the Washington, DC area, and will open the door to new projects and funding opportunities to further examine HIV associated cognitive problems during brain development within the Washington, DC research community.

The District of Columbia (DC) suffers from the highest rate of human immunodeficiency virus (HIV) infection per 100,000 in the United States. DC also has a high rate of drug abuse and addiction. When people take drugs like heroin, cocaine, cigarettes, marijuana, alcohol, and others, they are more likely to get involved in risky behaviors that can lead to sexually transmitted or needle infection with HIV/AIDS. In the brain, mental health disease and addiction are processed in similar regions that lead to reduced feelings of pleasure. Research shows that the same pleasure centers in the brain that are affected in addiction and in mental health disease are places where HIV likes to hide and divide. In this research, we want to figure out if the progression of brain disease in HIV is related to if a person has DNA that makes them likely to become addicted to drugs, and if this affects the way they take their HIV medicine.

The researchers are conducting ongoing research in African-American patients with a history of drug (heroin) abuse, and our initial studies show a relationship between DNA risk genes and their addiction history. At present, it is not known if HIV infection is linked with genetic risk for addiction, and if this risk predicts whether people will stick to their HIV medication. Some studies show that there are specific regions in the brain, related to reward, that are the targets of HIV, but we don’t know if HIV impacts the long cable connections, axon fibers, between the reward centers and other brain centers. this study will test the theory that patients with genes for addiction risk are also at increased risk for HIV infection, and that internal connection patterns of neurons in the brain of chronic drug users will correlate with HIV disease and their adherence to therapy.

The results of this work will be shared with the general public at soon as it is available, through Washington DC Center for AIDS Research (DC-CFAR) sponsored events, throughout the community whenever possible, in academic circles, and through research publications. This work will have the broader impact to de-stigmatize drug abuse problems in the community, and to frame it as a genetic based disease that can be targeted for treatment.