Mission Statement

Investigating the genetic basis of virus resistance

Infectious diseases pose a severe threat to human life today as roughly one quarter of the human population is expected to perish due to infectious causes. In addition to the considerable morbidity caused by viruses, many deaths result from viral infection and most occur before the age of reproduction. Hence, viruses exert significant selective pressure on the human genome. However, genetic resistance to viral infection gives evidence of an ongoing evolutionary struggle between intrinsic resistance mechanisms and viral pathogens. Although many mechanisms have been identified, genetic resistance to viral infection is complex and is still poorly understood.

The Brown Lab in the Beirne B. Carter Immunology Center at the University of Virginia has made important discoveries related to understanding how Natural Killer (NK) cells mediate antiviral immunity and a genetic basis for resistance to viral infection. We have identified and characterized various genes that affect NK cell effector activities as well as their capacity to specifically respond and kill virus-infected target cells during infection. We have learned also that even subtle genetic changes can profoundly influence the extent of inflammation and tissue damage associated with virus infection and the ensuing immune response. Ongoing research in the laboratory focuses on discovering additional genetic factors in control of virus-induced inflammation and tissue damage, whether their effect is primarily at the level of NK cells or other types of immune cells that help to identify and clear viral pathogens from host tissues.

Exploring immunity to human lung cancer

Lung cancer is prevalent worldwide and non-small cell lung cancer (NSCLC) accounts for most of all lung cancer. Despite that patient lung tumors become infiltrated with immune cells, tumor-infiltrating lymphocytes in lung cancer typically display poor immune function for unknown reasons. Using advanced multi-color fluorescent imaging techniques, we analyze human immune cells found in resected lung tissue sections from lung cancer patients. We want to understand how and why NSCLC tumors continue growing in patients even though immune cells, including NK cells, are evident in these tumors.

Based on what we have learned about antiviral NK cells in mouse model systems described above, we hypothesize that NK cells may adapt to human lung cancer by turning down their functional response. To explore this possibility, we have analyzed and compared immune cell spatial profiles in the tumor microenvironment (TME) using computational approaches. We expect spatial profiling of immune cells in the TME will provide new understanding about antitumoral immunity and additional insight about how we might leverage NK cells to improve patient survival in the future.

For the most current list of Brown Lab publications, please see
https://www.ncbi.nlm.nih.gov/myncbi/michael.brown.1/bibliography/public/?sortby=pubDate&sdirection=ascending