Skip to main content
Sign In

DEPARTMENT OF IMMUNOLOGY & MICROBIOLOGY, A Leader in Immunology, Microbiology and Microbial Pathogenesis Research and Training

Immunology and Microbiology
 

Raul Torres, Ph.D.

Professor of Immunology & Microbiology, Immunology Graduate Program Director


12800 E. 19th Ave., RC1-N 8107
Mail Stop 8333, Aurora, CO 80045
Phone: 303-724-8669

E-mail: raul.torres@ucdenver.edu

We have a long-standing interest in investigating the mechanisms by which B lymphocytes develop and subsequently mount antibody responses to foreign antigens and pathogens.  In the recent past we have particularly focused on understanding how the distinct B cell populations that exist in humans and mice act in concert to provide humoral immunity.  To address these issues, we rely on molecular, genetic and biochemical in vitro and in vivo approaches that often rely on genetically-engineered mouse models.  More recent work in our lab has revealed that a bioactive lipid, lysophosphatidic acid (LPA), is able to suppress signaling by both B and T lymphocyte antigen receptors and specifically upon engagement with the LPAR5 receptor. Furthermore, we have shown that LPAR5-deficient B cells mount heightened antibody responses and LPAR5-deficient tumor-specific CD8 T cells are better at controlling tumor growth compared to wild type cells.  Below are a couple of the research projects currently underway in our lab.

Autoreactive B cell contribution to humoral immunity
The ability of an antibody to recognize its cognate antigen has historically been referred to as “lock-and-key” to imply exquisite specificity.  However, both healthy humans and wild type mice harbor mature B cells with B cell antigen receptors (BCRs) that have multiple specificities, including specificity for self. Intriguingly, many of these auto-reactive specificities are encoded by evolutionarily conserved IGVH gene segments; although why the immune system has evolved and maintained germline encoded self-specificities remains speculative. Furthermore, these auto-reactive BCRs can also recognize epitopes on pathogens (i.e., are poly-reactive) and have been documented to mount protective antibody responses against both bacteria and viruses, including HIV.  In contrast to this protective role, poly-/auto-reactive B cell numbers are also elevated in autoimmune individuals and the antibodies produced by these cells contribute to autoimmunity. Thus, a major current project in our lab is to understand how these auto-reactive B cells escape B cell tolerance to mount antibody responses or, conversely, contribute to autoimmunity.  

Tumor-derived LPA suppression of CD8 T cell tumor immunity
It is now clear that tumors promote a microenvironment that specifically suppresses CD8 T cell immunity and therapeutics that interfere with this immune suppression have shown great recent success in the clinic for the treatment of certain malignancies. Recent work from our lab has found that lysophosphatidic acid (LPA), an extracellular lysophospholipid, inhibits CD8 T cell TCR signaling, activation and proliferation by signaling via the LPAR5 receptor. Of particular interest, tumors with diverse origins have long been known to aberrantly produce LPA, which in turn has been shown to promote tumorigenesis in an autocrine manner via different mechanisms.  Using a mouse model we have shown that LPAR5-deficient tumor specific CD8 T cells control an established melanoma better than wild type cells. Ongoing studies are now trying to better characterize how tumor-derived LPA not only promotes tumor growth but also leads to immune suppression of tumor-specific CD8 T cells.





Pamela Strauch, B.S. (University of California at San Diego)

Sr. Professional Research Assistant
pamela.strauch@ucdenver.edu


Kristen Shotts, B.S. (University of Colorado Boulder)
Graduate Student
kristen.shotts@ucdenver.edu

B cell antibody response to HIV



Divij Mathew, B.A. (Hamilton College)
Graduate Student
divij.mathew@ucdenver.edu 

Lysophospholipid regulation of lymphocyte function



Amanda Agazio, B.S. (Metro State University)
Graduate Student
amanda.agazio@ucdenver.edu

Natural antibody regulation of B cell biology
  Dr. Torres runs a joint lab together with Dr. Roberta Pelanda.