University of Minnesota
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MICaB Faculty

Brian T. Fife, Ph.D.

Associate Professor

Department of Medicine

Northwestern University, 2001, Ph.D.

Office phone: 612-624-2417
Lab phone: 612-624-6149

Fife Lab webpage

Research Interests:

Autoimmunity, Cancer immunology, immunotherapy, T cell engineering, mAb engineering.

The immune system has evolved to help protect the body from foreign invading pathogens. To accomplish this critical role, T lymphocytes must discriminate between self and non-self. This property translates into the immune recognition and elimination of infectious invaders while leaving host tissues intact.  In the Fife lab we are interested in situations where immune recognition is ineffective (tumor immunity) or over active (autoimmunity).

T cell function is negatively regulated by several inhibitory receptors, including Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed Death-1 (PD-1). Our research is focused on understanding their biology as well as discovering/applying novel methods to deliver agonist signals to control autoimmunity, or to disable these pathways (checkpoint blockade) to enhance tumor immunity. We have shown that CTLA-4 and PD-1 control both anergy induction and long term maintenance of tolerance using an autoimmune diabetes model. In the tumor microenvironment, CTLA-4 and PD-1 can be selectively targeted to restore T cell function and re-invigorate an exhausted T cell response. However, checkpoint therapy can also lead to adverse events including autoimmunity in some patients. Understanding the intricate balance between tumor immunity and autoimmunity is a critical question in health care today, and is an active area of research in our lab.

In addition to studying immune checkpoint or regulatory pathways controlling T cell function (Regulatory T cells, Tregs), we are also focused on understanding antigen-specific lymphocyte interactions in autoimmunity and tumor immunity.  Recently we have refined a method to efficiently generate monoclonal antibodies that can be used to target specific T cell populations during autoimmunity or tumor immunity.  We also study antigen-specific lymphocyte responses using peptide:MHC tetramer reagents to understand tolerance induction and mechanisms of diabetes resistance. We recently began studies using chimeric antigen receptor (CAR) T cells to control tumors or enhance T cell control during autoimmune disease. With a better understanding of immune control and the intricate balance of immune activation and regulation we will be able to design antigen-specific therapies to help control tumors or prevent autoimmunity.

Publications at Pubmed