The physiological stress response facilitates flight or fight responses and potentiates chances of survival by dilating pupils and increasing energy mobilization, heart rate, respiration, and blood flow to skeletal muscles. Current research indicates that potentiated innate immunity due to the release of danger-associated-molecular-patterns (DAMPs) should be added to this list.
This project focuses on the role of the stress-inducible member of the 70-kDa Hsp (heat-shock) family of proteins Hsp72, as an important systemic DAMP. The discovery of Hsp72 as a DAMP would have implications for all organisms that generate adaptive acute stress responses. Using a systems biology approach, this project examines the nature of eHsp72 release and its function in host defense following bacterial challenge. The results of this work will enrich the interplay of research between the fields of stress physiology and immunology and could yield ways of capitalizing on the adaptive aspect of stress. In addition to specific scientific advancements, this research will sustain recruitment of undergraduate students from underrepresented minority groups in the biological sciences, with the goal of preparing them to enter graduate school.
The PI has historically trained and mentored undergraduate students from underrepresented groups. Students involved in the project will be mentored and trained in research design, critical thinking, oral and written communication. Undergraduate students will present their work at scientific meetings and in peer-reviewed journals as co-authors. The project outcomes will be disseminated to the general public through television, radio, and mainstream periodicals.
Intellectual Merit: The physiology of the stress response facilitates flight or fight responses and potentiates chances of survival by dilating pupils and increasing energy mobilization, heart rate, respiration, and blood flow to skeletal muscles. We investigated the hypothesis that potentiated innate immunity due to the release of danger associated molecular patterns (DAMPs) should be added to this list. The focus of this proposal is on the role of the stress-inducible member of the 70-kDa Hsp family of proteins Hsp72, as an important systemic DAMP. The discovery of Hsp72 as a DAMP would have implications for all organisms that generate adaptive acute stress responses. For example, due to the presence of DAMPs, the gazelle running across the savanna being chased by the lion will reap the benefit of faciltated innate immunity if wounded and/or exposed to pathogen. Using a systems biology approach, this proposal examined the nature of eHsp72 release and its function in host defense following bacteria challenge. Specifically, we discovered that stress-induced sympathetic nervous system activation is responsible for the release of eHsp72 into the blood and that the released eHsp72 is associated with exosomes. Our results successfully revealed a novel physiological function of exosomes and fundamentally changed our understanding of the physiology of the acute stress response to include the release of endogenous immunomodulatory "alarm signals" that function to facilitate innate immune responses and improve our chances of survival. This work has been shared with the scientific communities through peer-reviewed publications (5 in review, 9 published) and oral presentations both nationally (10 talks) and internationally (4 talks). Broader Impacts: My laboratory trained and mentored graduate and undergraduate students from various ethnicities (African American, Hispanic, Vietnamese, Arabic, and Interracial). The proposed research program provided a platform that allowed successful launching of several students from underrepresented minority groups into a future career in the biological sciences, including additional education in veterinarian school, medical school, graduate school and nursing. Successful students mastered skills involving research design, critical thinking, oral and written communication. Both undergraduate and graduate students were provided opportunities to will present their work at scientific meetings and to publish their work in peer-reviewed journals. Our findings were also shared with the general public through television (PBS), radio (NPR), and community lectures (Louisville Library). Lastly, my laboratory findings were successful in revealing new information about the interplay between stress physiology and immunology.
