Herbert L. Mathews, PhD

Physiological and psychological stressors impact the immune system, resulting in the dysregulation of normal immune homeostasis. Such dysregulation has a particular impact upon individuals who are already debilitated or are compromised by medical intervention. These individuals are especially susceptible to invasive agents either of exogenous or endogenous origin. It is the focus of this laboratory to understand the impact of these stressors upon the immune system, to determine the molecular basis by which immune dysregulation results from these stressors, and to explore methods by which to return the immune system to normal homeostasis.

Our approach is an integrative one in which interactions among the nervous, endocrine, and immune systems are analyzed within the framework of psychoneuroimmunology. Research is focused on the physiological impact on the immune system of breast cancer, surgery for radical prostatectomy and for herniated disk repair, as well as for patients with multiple sclerosis. The impact of pain and/or mood disturbance are analyzed for their psychological effect on immune function. We have identified specific and unique effects of these stressors on cytokine expression, immune cell targeting, and upon the trafficking and release of immune effector cell populations. These identified effects are at the cellular level and differ for each of these physiological and psychological stressors.

This work has been most fully realized with breast cancer patients and has led to an understanding of the effects of psychosocial distress upon peripheral blood mononuclear cells of patients undergoing diagnosis and treatment. The cellular focus has been on the development of techniques and procedures to analyze surface, cytoplasmic and nuclear protein expression in peripheral blood mononuclear cells derived from these patients. The molecular focus of that work has been both global and local and in relation to immune effector genes, immune effector function and to the physiological and psychological constructs of the subjects. The most recent work seeks to understand the epigenetic basis for psychosocial-distress mediated immune-dysregulation by analysis of histone modification and DNA methylation in vulnerable populations undergoing either an immediate or protracted stress response. Epigenetic analysis is accomplished in the context of the functional properties of the patient’s immune system. This work was among the first to demonstrate an epigenetic influence of psychosocial distress on immune effector function and inflammatory cytokine production in human peripheral blood mononuclear cells. Of particular relevance are the published data demonstrating capacity for measurement of; nuclear levels of histone post translational modifications as well as cytoplasmic levels of immune effector molecules including proinflammatory cytokines. Detailed epigenetic analysis is accomplished with chromatin immunoprecipitation, qRT-PCR and by the evaluation of relative chromatin accessibility for relevant immune effector genes.

It is our ultimate goal to delineate the molecular basis for these differences and to devise the means by which to counteract them at both the cellular and molecular level. With this in mind, our current focus is upon the influence of epigenetic modifications both those which influence histone post translational modifications and those that influence DNA methylation.