Immunobiology and Stress Response Laboratories
Dr. Carol Miller-Graziano, Director
Research Overview
The overall laboratory hypothesis is that unbalanced monocyte differentiation to inflammatory macrophage versus immunostimulatory dendritic cells results in cytokine shock and immunosuppression in traumatic patients. Post injury alterations in monocyte (MØ) receptor expression and stimulation are examined at the molecular (PCR, RPA, Microarray) cell expression (flow cytometry) and signal transduction levels assessed as pivotal in altered MØ differentiation. Early post injury mediators like prostaglandins and heat shock proteins are being assessed as triggers for these receptor changes. The induction of anergic and/or regulatory T lymphocytes by dysfunctional dendritic cells is explored. Altered T cell activation, apoptosis and function are also assessed in molecular and signal transduction experiments. Regulatory and anergic T cells are being distinguished by unique receptor expression and signaling. Finally, in combination with 11 other medical centers including Stanford, Harvard, Washington U., Northwestern, and the University of Washington, we are identifying chemokine and other surface phenotypic markers for patients' developing immunoaberrances. Microarray analysis is also being used to identify novel targets for immunomodulation in these patients with systemic and chronic inflammatory pathology.
Stress Response Faculty Investigators - Projects
- Dr. Paul Bankey, Chief Division Trauma and Critical Care - Epidermalogical and genetic changes in major trauma patients; Neutrophil activation and derangement after trauma.
- Dr. Asit De - Unique phenotypes expressed in trauma patients. In vivo affects of HSP-27 in a rat model; Dendritic cell maturation in cancer patients.
- Dr. Krzysztof Laudanski - Microarray analysis of aging effect on dendritic cell maturation; effect of injury on monocyte/macrophage/dendritic cells in the lung.
Clinical Co-Investigator:
Christopher Lentz, Director Burn Center - Altered aveolar macrophage function in burn patient's bronchial lavage.
Laboratory Personnel:
- Technical Support: Jennifer Lonowski, Amanda Black, LeAnne Staples, Mita De, Sarah Roach, Irene Steele, RN.
- Current Trainees: Robin Minielly, Dorota Wyczechowska, Lanyn Perez, Mike Springer.
Administrative and Accounting Support:
Joyce Krieger, Mariellen Blossom, Judy Hawkins.
Research Grant Support:
- Do Anergic T-Cells Intensify Post-Trauma Immunosuppression?
NIH - NIGMS, Carol Miller-Graziano, PI, Krzysztof Laudanski and Asit De, Co-PI. - Is Aberrant Monocyte Stimulation Pivotal in Post-Trauma MODS?
NIH - NIGMS, Carol Miller-Graziano, PI, Krzysztof Laudanski, Co-PI. - Large Scale Collaborative Project: Inflammation and the Host Response to Injury - Proteomics & Genomics Cores, MGH / NIH, Carol Miller-Graziano, PI, Paul Bankey, Krzysztof Laudanski and Asit De, Co-PI.
- Large Scale Collaborative Project: Inflammation and the Host Response to Injury - Clinical Core, MGH / NIH, Paul Bankey, PI, Carol Miller-Graziano, Co-PI.


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