Schaller Lab

About 1/3 of the world has the disease Tuberculosis, which is caused by infection with the bacteria M. tuberculosis. At present, there are no vaccines that confer lifelong protection against M. tuberculosis infection. The World Health Organization states that Tuberculosis is one of the top 10 causes of death worldwide. We are researching why the immune system fails in eliminating M. tuberculosis, with the goal of improving the immune response to this pathogen.

Under normal circumstances, our immune system is able to eliminate pathogens through the regulation of gene expression. For example if a host is infected with influenza, B cells will upregulate the expression of antibodies that bind to the influenza virus and thus prevent future infections. In these cases the duration of the illness is short-lived. Immune system exposure to the pathogen, and the resulting regulation of gene expression, aids the immune system in remembering that specific pathogen so that the host cannot get re-infected. Immune cell education is done both by direct exposure to the pathogen itself and also through the activity of cytokines – chemical messengers that cells produce to educate other cells around them of ongoing inflammatory events.

Sometimes the immune response to a pathogen goes awry. This is especially true in cases where the infection never clears, which is what happens when an individual is infected with the M. tuberculosis bacteria. M. tuberculosis can cause permanent changes in the way an immune system responds to infection through improper regulation of gene expression. As evidence of this, those patients that are contagious for M. tuberculosis have an altered cytokine profile compared to individuals that have contracted the disease but do not spread it. This aberrant regulation of gene expression likely contributes to conditions that favor the growth and persistence of the M. tuberculosis bacteria inside the host. If we can understand the process through which immune cells are educated in an improper manner as a result of M. tuberculosis infection, we can use that knowledge for new treatments and diagnostics for Tuberculosis. We may also be able to use this knowledge to develop vaccines that prevent infection from occurring.

Relevant Publicatons

  • Ting H-A, Schaller MA, Nagata DE de A, Rasky AJ, Maillard IP, Lukacs NW. Notch Ligand Delta-like 4 Promotes Regulatory T Cell Identity in Pulmonary Viral Infection. The Journal of Immunology. 2017 Feb 15;198(4):1492–1502. PMID: 28077598
  • Bermick JR, Lambrecht NJ, denDekker AD, Kunkel SL, Lukacs NW, Hogaboam CM, Schaller MA. Neonatal monocytes exhibit a unique histone modification landscape. Clin Epigenetics. 2016;8:99. PMCID: PMC5028999
  • Schaller M, Ito T, Allen RM, Kroetz D, Kittan N, Ptaschinski C, Cavassani K, Carson WF, Godessart N, Grembecka J, Cierpicki T, Dou Y, Kunkel SL. Epigenetic regulation of IL-12-dependent T cell proliferation. J Leukoc Biol. 2015 Oct;98(4):601–613. PMCID: PMC4763868
  • Schaller MA, Allen RM, Kimura S, Day CL, Kunkel SL. Systemic Expression of Notch Ligand Delta-Like 4 during Mycobacterial Infection Alters the T Cell Immune Response. Front Immunol. 2016;7:527. PMCID: PMC5121470

A full list of peer-reviewed publications can be viewed here: