Lund Lab

The Team

Frances Lund, Ph.D.
Jessica Hoffman, B.S., Senior Technical Associate
Elizabeth (Lizz) LaMere, B.A., Senior Technical Associate
Beatriz Leon-Ruiz, Ph.D., Postdoctoral fellow
Kyle Martin, B.S., Tech IV
Ravi Misra, Ph.D., Postdoctoral fellow
Betty Mousseau, A.A.S., M.T., Senior Technical Associate
Wojciech Wojciechowski, Ph.D., Postdoctoral Fellow

Dr. Lund's Research Interests

The research goals of the Lund laboratory are:

For many years, we have been interested in determining the mechanisms that regulate leukocyte trafficking to sites of inflammation and infection.  In one project, we are evaluating whether blocking the migration of inflammatory cells such as monocytes and macrophages to the lung reduces the pathology associated with virulent influenza virus infections.  In a second project, we are studying a novel “alternative” chemokine receptor signaling pathway that we recently characterized.  Similar to the “classical” signaling pathway, the alternative chemokine receptor pathway is activated by Gai2-containing G proteins.  However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins.  We showed that Gaq deficient monocytes and dendritic cells are not competent to migrate into inflammatory sites and lymph nodes in vivo, demonstrating the critical importance of this novel alternative pathway in inflammation. Interestingly, we showed that the Gaq-coupled chemokine receptors are further regulated by two novel calcium mobilizing metabolites, cADPR and ADPR, produced by the NAD-utilizing ecto-enzyme CD38. 

Our newest studies are aimed at asking whether we can identify other additional key signaling molecules in the pathway that could be targeted by drugs to inhibit the alternative chemokine receptor signaling pathway in diseases such as asthma and atherosclerosis.   In addition to studying how the calcium second messengers made by CD38 impact cell migration and inflammation, we are also evaluating whether CD38 regulates the NAD metabolome in cells. In recent experiments, we and others demonstrated that CD38 regulates NAD homeostasis in multiple tissues.  We further showed that CD38 modulates the activity of several other important NAD-catabolizing enzymes that are involved in DNA repair, cell survival and oxidative stress responses. 

Our future goals are to determine whether enhancing or suppressing CD38 enzyme activity can be used to alter cellular responses to agents that cause DNA damage.  Finally, a major goal of my lab is to evaluate the multiple protective and damaging roles of B cells in infection and autoimmune disease.  A number of years ago, we demonstrated that B cells secrete distinct arrays of cytokines in response to antigen, T cell help and the cytokine microenvironment in which the B cells were primed.  Since that time, we phenotypically and functionally characterized the different cytokine producing effector B cell subsets using a variety of approaches including microarray analysis.  In addition, we directly tested the relevance of cytokine-producing B cells in protection to multiple pathogens and found that B effector cells play a key role in regulating both humoral and cellular immune responses.  Our current focus is to identify these effector B cells in humans, to determine whether effector B cells contribute to pathology associated with a number of autoimmune diseases including Type I Diabetes, Rheumatoid Arthritis and Lupus and to assess whether one of the protective effects of B cell depletion therapy in human patients is due to the elimination of these potentially pathogenic effector B cells.

Funding

Dr. Lund receives her funding from the NIH, Boehringer Ingelheim, and the United States-Israel Binational Science Foundation.

Relevant Publications