Dr. Roberts' Research Lab

The goal of my laboratory is to understand the role of proteolysis in disease. Proteolysis is the enzymatic breakdown of proteins. We are currently working on the role of proteolysis in Systemic Lupus Erythematosus (SLE). This autoimmune disease afflicts mainly women and is influenced by hormones such as estrogen. Among the disease processes associated with SLE are altered apoptosis and the production of antibodies autoreactive to targets such as histones, DNA, RNA, cathepsin G, and the proteasome. Part of the immune system called MHC class-II antigen presentation may play a role in the disease and SLE patients display enhanced levels of MHC class-II. Proteolysis is a fundamental element of MHC class II antigen presentation. Lysosomal proteases called cathepsins are necessary for both the generation of antigenic epitopes and the degradation of the MHC class II-associated invariant chain (Ii). The ability to characterize the regulation of the proteases involved in these processes is essential in understanding MHC class II antigen presentation in general and within the context of SLE.

The link between SLE and sex hormones such as estrogen is documented, yet the mechanism of action remains unknown. Estrogen has been shown to alter the gene expression of cathespin D. Cathepsin expression and activity may be influenced directly by estrogens or indirectly via a change in cytokine profiles.

Environmental estrogens such as bisphenol A (BPA) may act as immune modulators and affect disease progression. BPA is used in the manufacture of polycarbonate plastics and epoxy resins widely found in food containers. It is also a component of dental sealants and is released into the saliva following application. While structurally different from estrogen, BPA binds and activates estrogen receptors with high affinity. A recent report by the CDC indicates that over 90% of Americans have BPA in their bodies. In 2008, a panel put together by the National Toxicology Program reviewed the current literature and determined that BPA can affect the brain, behavior, and prostate in fetuses, infants and children and may affect mammary glands and result in early onset of puberty in females. However, few papers have been published concerning BPA and immune function.

My lab investigates the effect of hormones (natural and environmental; specifically estrogen and BPA) on the proteases involved in MHC class II antigen presentation in NZB/NZW (Lupus-prone) and control mice to better understand the relationship between hormones and SLE progression.  We have determined that the activity of cathespins B and L are altered in immune cells when exposed to estrogen and BPA, while cathepsin S does not appear to be regulated by these chemicals.

Students working in my lab will have the opportunity to become proficient in cell culture, SDS-PAGE, western blot, animal maintenance & handling, protein assays, enzyme assays, and other general biochemical techniques and data analyses.


Structure of
procathepsin B


Allison Young (BIO '10)
and Matt Zuber (BCMB
'11)


Laura Seczech (BIO '09), 
Bill Stanert (BCMB '08),
and Emily Mercadante
(BCMB '10)

 


Caroline Biswanger
(BIO '05), Ryan Lenhart
(BIO '06), Dr. Rebecca
Roberts

 


Tom Seegar (BCMB '04)
and Danielle Falkowski
(BCMB '06)

 


Derese Getnet (BCMB '04)
and Ella Lazo (BIO '04)

 


Ryan Lenhart (BIO '06)
wins award at Mid-
Atlantic Pharmaceutical 
Society conference