Lora Hooper, Ph.D.
Assistant Professor of Center for Immunology & Microbiology

Office: 214-648-7306
Email: lora.hooper@utsouthwestern.edu

The human intestine harbors a vast and complex society of bacteria that is present starting at birth and persists throughout life.  Our relationship with our indigenous bacteria has evolved over millions of years of co-existence.  For the most part, we enjoy a mutually beneficial relationship with these microbes.  However, we still understand very little about how such beneficial host-bacterial relationships are established and maintained, or how resident gut bacteria communicate with our own cells.

Intestinal immune cells develop in intimate contact with these large bacterial populations (known as "commensals").  We currently know very little about how much of our gut immune system's maturation and function is shaped by interactions with commensal bacteria and how much is hard-wired in our own genes.  To address this question, my laboratory has established a germ-free mouse colony where mice are raised under completely sterile conditions inside plastic germ-free isolators.  By comparing intestinal immune cells from germ-free mice with those from normal, non-sterile mice, we can determine how indigenous gut bacteria influence the development and function of the mucosal immune system.

One research program in the lab is focused on understanding how commensal bacteria contribute to the development of intestinal innate immunity.  These studies focus on bacterial interactions with Paneth cells, specialized epithelial cells that secrete large quantities of antimicrobial proteins.  We are using our germ-free mouse model to understand how commensal bacteria actively alter the composition of the Paneth cell antimicrobial arsenal by modulating cellular gene expression.  We are also seeking to identify bacterial signals that are exchanged with the Paneth cell and to understand how these cells convert bacterial signals into changes in antimicrobial gene expression.  Finally, we are using biochemical approaches to understand how certain Paneth cell antimicrobial proteins carry out their "seek and destroy" functions.

A second research program in the lab is focused on understanding how commensal bacteria shape adaptive immunity in the gut.  Our approach involves applying DNA microarrays to our germ-free model system to delineate how gut commensals modulate gene expression in intestinal T lymphocytes.  In this way, we hope to understand how commensal bacteria contribute to gut T cell development and function.

Our overall goal is to understand how bacteria and host collaborate to establish and strengthen the intestinal barrier.  These studies will be important for understanding the molecular basis of inflammatory bowel disease, which affects more than 1 in 1000 individuals in the United States.  Furthermore, we expect that our research will provide insights about the potential effects of broad-spectrum antibiotic use on the intestinal immune system.  Ultimately, we hope that our results will point to new strategies for harnessing the power of our bacterial allies in fortifying the lining of the gut.

Selected Publications:

Hooper, L.V. (2004)  Laser microdissection:  Exploring host-bacterial interactions at the front lines.  Current Opinion in Microbiology 7, 290-295.

Hooper, L.V. (2004)  Bacterial contributions to mammalian gut development.  Trends in Microbiology 12, 129-134.

Xu, J., Bjursell, M.K., Himrod, J., Deng, S., Carmichael, L.K., Chiang, H.C., Hooper, L.V., and Gordon, J.I. (2003)  A genomic view of our symbiosis with Bacteroides thetaiotaomicron.  Science 299, 2074-2076.

Hooper, L.V., Stappenbeck, T.S., Hong, C.V., and Gordon, J.I. (2003) Angiogenins: a new class of microbicidal proteins involved in innate immunity.  Nature Immunology 4, 269-273.

Stappenback, T.S., Hooper, L.V., and Gordon, J.I. (2002) Development regulation of intestinal angiogenesis by indigenous microbes via Paneth cells.  Proceedings of the National Academy of Sciences USA 99, 15451-15455.

Hooper, L.V., and Gordon, J.I. (2001) Commensal host-bacterial relationships in the gut.  Science 292, 1115-1118.

Hooper, L.V., Wong, M., Thelin, A., Falk, P., Hansson, L., and Gordon, J.I. (2001) Molecular analysis of commensal host-microbial relationshiops in the intestine.  Science, 291, 881-884.