The Division of Investigative Pathology is the basic research intensive arm of the Department of Pathology and has been headed by Dr. Alexzander A. A. Asea since its establishment on May 2005.

Current research in the Division of Investigative Pathology is focused primarily on:

1. The research & development of heat shock-based drugs.

2. Understanding the mechanism by which these drugs function, so that we can develop even more potent drugs.

3. Education and training of the local community on recent advances in drugs therapies.

Our research involves multidisciplinary programs; working closely with basic academic research scholars, translation drug discovery based researchers, population and clinical research scientists. Our programs are designed to enable High School Students, Undergraduate and Graduate Students, Postdoctoral Scholars, Medical Residents and Junior Faculty gain fundamental, hands-on knowledge about the role of heat shock proteins (HSP) in a number of human disease and disorders for the benefit of human health. Our projects utilize animal models, novel cellular and molecular biology techniques to elucidate and enhance novel host defense mechanisms. Our experimental approaches utilize:

• RNAi Technology
• Hyperthermia/Thermal Stress Techniques
• Nanotechnology
• Proteomics Core Facility
• Flow Cytometry Core Facility

Dr. Asea's initial observations studying the effect of heat shock proteins on human monocytes lead to a paradigm shift in our understanding of the role of heat shock proteins. Thus, heat shock proteins previously known to be an intracellular molecular chaperone, can be found in the extracellular milieu where it has regulatory effects on immunocompetent cells (Fig 1). Additional discoveries including the recent finding that surface expression of heat shock proteins differentially regulate tumor growth and metastasis, and that silencing these proteins eliminates the migration capability of the highly metastatic breast adenocarcinoma in vitro and in vivo, has opened a new front in the fight against breast cancer with the introduction of NampEVA.

Figure 1. 

Fig 1. Model for stress-induced release of Hsp72 into the circulation. Stress can either induce cell death by activating the death pathway or activate the cellular stress response, which stimulates synthesis of intracellular Hsp72 known to inhibit cell death. Increased intracellular Hsp72 is expressed on the surface of cells and becomes a target for NK cell cytotoxicity. Intracellular Hsp72 is subsequently released into the extracellular milieu within exosomes and enters the circulation. Circulating extracellular Hsp72 (eHsp72) binds to APC and stimulates the chaperokine effect; cytokine, chemokine and reactive oxygen species release. In addition, peptides chaperoned by eHsp72 are processed and presented in the context of the MHC class I to stimulate specific CTL responses. Psychological stress and exercise induce the release of eHsp72 into the circulation by a hitherto unknown tissue or organ.