John H. Weis

Professor of Pathology

John Weis

B.S. Oregon State University

Ph.D. University of Minnesota Medical School

John H. Weis Memorial Graduate Student Award

 

Research

Our laboratory studies the interfaces between the innate and acquired immune responses. We take a genetics approach, using the mouse as a model system, to decipher molecular and cellular interactions.

One current focus in the lab includes the maturation and differentiation of B cells with the intent to identify key transcription control proteins that regulate this process.  Mouse B cells enter the spleen from the bone marrow requiring a number of maturation steps to insure they are competent to respond to antigen following an infection.  These immature B cells must negotiate through a series of differentiation checkpoints, requiring transcriptional induction and suppression of key target genes.  We have identified a number of the target gene products required for such maturation and have created conditional mouse knockouts that eliminate the expression of that gene during B cell maturation.  We are currently analyzing cells from such animals for B cell functions and development.

Another focus of the lab is on the functions of the innate response Interferon-inducible transmembrane (Ifitm) proteins.  These proteins are known to inhibit virus infections (HIV, influenza, etc).  We possess a mouse that lacks all of the five members of this family.  Cells from this mouse (after immune activation) demonstrate a loss of clathrin from membrane compartments, an inhibition of clathrin-mediated phagocytosis, and a decrease pH of phagocytic endosomes.  We have demonstrated that one specific Ifitm protein, Ifitm3, physically stabilizes the vATPases present in the endosome membrane, and is required for its function in lowering the pH of the endosome and thus establishing an antiviral state. We are continuing this work by more closely examining the binding of Ifitm3 to the vATPase as well as examining other Ifitm biding proteins in the cell.

The last project in the lab has been to study the structure, expression and function of a set of mouse proteins known as the complement receptors, Cr1 and Cr2.  These proteins are critical for controlling complement activation during immune reactions and serve to assist in the production of the full range of B cell products. Inappropriate expression of such proteins (such as engineered mouse anomalies or human deficiencies) can give rise to a range of symptoms including autoimmunity, susceptibility to natural infections and a degraded antibody response.  Both Cr1 and Cr2 are generated from a single gene by alternative splicing. We have created strains of mice deficient in both proteins, and strains deficient in only Cr1 or Cr2, and are analyzing them for immune deficiencies.

References

Selected Publications

  1. Debnath I, Roundy KM, Pioli PD, Weis JJ, JH Weis (2013) Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins. Int Immunol, 25(2):99-115
  2. Wee YS, Roundy KM, Weis JJ, JH Weis (2012) Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function. Innate Immun, 18(6):834-845
  3. Dahlem T, Cho S, Spangrude GJ, Weis JJ, JH Weis (2012) Overexpression of Snai3suppresses lymphoid- and enhances myeloid-cell differentiation. Eur J Immunol,42(4):1038-1043
  4. Roundy K, Jacobson AC, Weis JJ, JH Weis (2010) The in vitro derivation of phenotypically mature and diverse B cells from immature spleen and bone marrow precursors. Eur J Immunology, 40(4):1139-1149
  5. Debnath I, Roundy KM, Dunn DM, Weiss RB, Weis JJ, JH Weis (2008) Defining a transcriptional fingerprint of transitional B cell maturation. Genes and Immunity, 9(8):706-720
  6. Jacobson AC, Weis JJ, JH Weis (2008) Complement Receptors 1 and 2 Influence the Immune Response in a BCR-Independent Manner. J Immunol180(7):5057-5066

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Last Updated: 10/21/16