Our research examines how certain viruses like human immunodeficiency virus (HIV-1) and the human polyomavirus JC virus (JCV) affect the central nervous system (CNS) and impact brain cell function. HIV-1 is the virus that causes AIDS, and JCV can lead to a serious brain disease called PML (progressive multifocal leukoencephalopathy), especially in people with weak immune systems. 

We pioneered the use of a powerful gene-editing tool called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to fight these viruses. CRISPR works like a pair of molecular scissors to edit host genes that are targeted or used by viral DNA. It uses a guide RNA to find the exact spot in the DNA and a protein called Cas9 to cut it. This lets us remove or change the parts of human genes that viruses use to survive.  

Our team uses CRISPR to block the activity of HIV-1 and JCV. We are also testing how CRISPR works with other treatments such as antiretroviral therapy (ART), which is the standard treatment for HIV. Together, these methods may help eliminate viruses from host genes and support development of new treatments for CNS infections caused by HIV-1 and JCV. 

Our lab studies how HIV-1 enters the brain and how it interacts with drugs like opioids or methamphetamine. These interactions can disrupt the brain’s natural balance (homeostasis), leading to long-term problems with thinking, memory and mood problems.  

We are developing new treatments using the gene-editing tool CRISPR/Cas9 to cut out or change parts of both viral and human DNA. Our goal is to prevent or reverse brain damage caused by HIV and related neuroinflammation in people with HIV (PWH).  

As part of the Martin Delaney Collaboratory for HIV Cure Research, we work with partners to strengthen immune responses and eliminate latent HIV reservoirs that remain in the body even after treatment. We have built robust ex vivo latency models — lab-based systems using real cells outside of the body — to test and improve gene-editing constructs.  

Through translational research, we use CRISPR to target HIV, JCV, and  herpes simplex virus (HSV-1) in both in vitro (lab-based) and in vivo (in living systems) studies. We also support HIV neuropathogenesis research using the CNHC’s Mammalian Cell Culture Core by providing advanced 2D/3D CNS culture systems, viral tools and high-resolution functional and spatial analyses. Our integrated research model bridges basic virology, neurobiology, and translational gene therapy to advance treatments for neurovirological diseases. 

Our group is developing ways to use CRISPR-Cas9, a gene-editing tool, to fight viruses. We are using it in three main ways: 

1. Directly removing viral genomes from infected cells. This includes viruses like HIV-1 (which causes AIDS), HTLV-1 (a virus linked to cancer), and HSV-1 (herpes simplex virus). 
2. Targeting and disrupting certain host dependency factor genes, which are genes in human cells that viruses need to grow and spread. These include ALCAM, CCR5, and MOGS. By turning off these genes, we may be able to limit how viruses grow and spread. 
3. Boosting genes like CD16, CISH, CXCR3, CXCR6, IL-15/IL-15Ra, and PD-1. These genes help cytotoxic immune cells — a type of white blood cell — move to infected tissues and destroy virus-infected cells. 

We have also studied JC virus (JCV) and SARS-CoV-2 (the virus that causes COVID-19). Since 2017, Dr. Kaminski has advised researchers from Philadelphia and beyond about how to use CRISPR-Cas9 in their own projects. 

Our lab studies how JC virus (JCV), a human polyomavirus, copies itself and activates its genes during infection. JCV can cause a serious brain disease called progressive multifocal leukoencephalopathy (PML) in people with weakened immune systems, such as those with AIDS, multiple sclerosis, or Crohn’s disease. 

We focus on a viral protein called agnoprotein, which plays an important role in the virus’s life cycle. This protein interacts with many parts of the infected cell, including the mitochondria — the parts of cells that produce energy. We are studying how agnoprotein affects mitochondria and whether this might be linked to brain diseases that come with aging, like Alzheimer’s disease.  

We also have made significant discoveries about another JCV protein called ORF4. In people with PML, ORF4 changes the location of special structures in the cell’s nucleus called nuclear bodies (NBs). This may block the cell’s interferon defense system, which normally helps fight viruses. We are using lab-grown cells and mouse models to learn more about how ORF4 works and how it helps JCV cause disease.

Our lab studies how JC virus (JCV) stays hidden in the body (a stage called latency) and what causes it to become active again (reactivation). We want to understand how JCV reactivation may be triggered by the body’s DNA damage response — a process that repairs broken DNA — and how this connects to a key signaling pathway called NF-kB, which helps control inflammation and the immune system. 

We are also studying epigenetic events, which are chemical changes to DNA that turn genes on or off without changing the DNA sequence itself. These changes may play a role in how JCV stays inactive or becomes active again. 

Our team works with other CNVGE researchers to explore new treatments for viral infections. We use the powerful gene-editing tool, CRISPR/Cas9, to see if it can remove viruses like JCV from infected cells. 

By understanding how JCV hides, reactivates, and affects the brain, we hope to develop better ways to prevent or treat diseases like progressive multifocal leukoencephalopathy (PML).