Research - Laboratory of Livia Casciola-Rosen, Ph.D. and Antony Rosen, M.D.

Erika Darrah

I am a Ph.D. student in the Immunology Graduate Program and am one of the newer additions to the Rosen Lab. I received a B.S. in Biology from Ursinus College and subsequently worked as a lab technician studying synaptic transmission in C. elegans. Upon entering graduate school at the Johns Hopkins University School of Medicine, I rotated in the Rosen Lab and explored the role of barrier-to-autointegration factor (BAF) as an autoantigen in the pathogenesis of lupus.  I am currently investigating the roles of perforin and granzyme B in granule-mediated cell death. Specifically, I am interested in the interplay between granule components as well as their trafficking within target cells.

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Dennise Duan-Porter

I am studying the altered structure and immunogenicity of nucleophosmin (NPM1), a tumor antigen in hepatocellular carcinoma that is targeted by autoantibodies in these patients.  We have observed that NPM1 was not only over-expressed in tumor tissue, but also behaved differently by biochemical analyses than NPM1 from normal or cirrhotic liver tissues.  Specifically, tumor NPM1 formed SDS stable oligomeric complexes and was highly susceptible to cleavage by granzyme B, a very fastidious serine protease.  Similar properties were observed with a mutant form of this protein beginning at the seventh methionine instead of the first (M7-NPM), making M7-NPM a good model for the tumor protein.  Using a variety of techniques, we are currently investigating the conformational and functional differences between wild-type NPM1 and M7-NPM.

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John Hall, Ph.D. Candidate

A graduate of Brown University, I joined the Rosen Lab full time in the spring 2001 as a student in the Graduate Program in Immunology.  My research has focused on the role of type I interferons in autoimmune disease.  I began my studies analyzing interferon-responsive autoantigens and more recently have been dissecting the “IFN signature” identified in SLE and Dermatomyositis.  I have been attempting to identify relevant pathways of gene expression which may lead to the propagation of an autoimmune response.  Understanding the mechanisms which target specific tissues for destruction by the immune system will be critical for future management and treatment of rheumatic diseases.

Michelle Harris, Ph.D.

I am a recent graduate of the Cellular and Molecular Medicine Ph.D. Program here at the Johns Hopkins School of Medicine.  Currently, I am finishing up work relating to my thesis project.  As I move on from here I will continue post-doctoral research in the general area of autoimmune disease.

The cytotoxic lymphocyte granule protease, granzyme B (GrB), appears to play a role in autoantigen selection in systemic autoimmunity.  In rheumatoid arthritis (RA), the noncoded amino acid, citrulline, is a frequent and specific target of autoantibodies.  Citrulline is formed by the post-translational deimination of arginine in a reaction catalyzed by peptidylarginine deiminases (PADs), one of which, PAD4, has been genetically associated with RA.  We have made the exciting discoveries that PADs can be cleaved by GrB and that PAD4 is itself a highly specific autoantigen in RA.  To gain a better understanding of disease pathogenesis, we are characterizing anti-PAD4 as a disease marker, and are investigating the interaction between PAD4, GrB, and anti-PAD4 autoantibodies.

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Katy Roberts Marron

As a graduate student in the Graduate Training Program in Cellular and Molecular Medicine, my research interest has been focused on the study of what happens to the Golgi apparatus during apoptosis.  We are interested both in the overall fate of the Golgi apparatus, as well as in specific proteolysis of the golgin family of autoantigens localized to the Golgi apparatus during cell death.  Since the Golgi apparatus is central in the secretory pathway, and many viruses rely on the host cell secretory pathway for the production of new virions, we are particularly focused on apoptosis mediated by cytotoxic lymphocyte granule exocytosis as this pathway of inducing apoptosis is critical in the elimination of many types of viral infections.  We hypothesize that rapid disruption of the secretory pathway in virally infected cells killed as part of the immune response to viral infection could be a potent antiviral activity, helping to  reduce the spread of virus to neighboring healthy cells.  

After graduation I am going to be a secondary school biology teacher.  In addition to teaching my long term interests include future involvement in science education policy and/or curriculum design and implementation.
   
  

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Tomeka Suber, MD/PhD Candidate

I am an MD/PhD student in the Cellular and Molecular Medicine Graduate Program.  I graduated from the University of North Carolina with a BS in Chemistry in 2002.  I am currently studying how various physiologic states of specific cell populations affect the expression and modification of common autoantigens.  I am exploring developmental, proliferative, and proinflammatory pathways to understand how autoantigen levels are attenuated in vitro and in lupus mouse models.  Understanding these mechanisms will also help clarify the connection between autoimmune disease and cancer.  Along with my research interests, I also mentor minority premedical undergraduate students, and I am active in the Student National Medical Association.  After completing the MD/PhD Program, I plan to enter into an internal medicine residency program and to specialize in oncology or rheumatology.

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Toni Hines

Toni is a technician working with Drs. Livia Casciola-Rosen and Antony Rosen.

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Marissa is a technician working with Drs. Livia Casciola-Rosen and Stuart Levine.

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