This application seeks funding for a T32 Training Program in Trauma, Burn, and Peri-operative Injury for 3 MD and 3 PhD trainees who will conduct trauma research in the laboratories of translationally oriented physician scientists and basic researchers at the Beth Israel Deaconess Medical Center (BIDMC) and other affiliated teaching hospitals of Harvard Medical School (HMS). The Harvard Longwood Medical Area holds an impressive array of clinical and research facilities that will be an ideal setting for the proposed T32 program, which will be the first of its kind in this area. The program will be directed by a multidisciplinary team of experienced leaders in the field of trauma, shock, and inflammation research. The research focus of this proposed program is centered on the early events leading to the inflammatory process and organ failure triggered by trauma with the aim of developing novel treatments to prevent inflammation to organ dysfunction. We propose a training program that will teach state-of-the-art knowledge in immunology, biochemistry, molecular biology, and the innate immune response to trauma. A long-term goal is to develop future leaders in the field of trauma research who have the necessary interdisciplinary teamwork skills that are required for to make tangible progress in the field. We propose to teach these skills by pairing MD and PhD trainees. These pairs will work in close interdisciplinary teams. MD trainees will help their PhD partners understand actual clinical problems in trauma care;PhD trainees will teach their MD partners how to address these problems with leading-edge science approaches. Both partners will lean how to communicate effectively with one another and how to solve real clinical problems in mutually beneficial interdisciplinary research teams. The need for this innovative training approach is driven by the following rationale: ? despite intense research efforts over several decades, inflammatory complications, immune dysfunction, and organ failure have remained major causes of post-traumatic morbidity and mortality. ? Remarkable progress in clinical trauma care and vast improvements in our understanding of the immunological, cellular, and molecular processes that drive post-traumatic inflammation have not translated into corresponding improvements in clinical outcome. ? A core reason for this deficit is inadequate information flow among clinical and basic researchers. Thus, a new paradigm of science training is needed to raise leaders in trauma research who can bridge this gap by developing strong interdisciplinary teamwork skills that help them advance the field and improve clinical outcome after trauma. The program directors themselves have established such interdisciplinary partnerships and will therefore serve as role models. They have gathered an impressive group of highly respected and motivated basic researcher and clinical faculty who will mentor trainees in their laboratories. We propose a program that will host 3 MD and 3 PhD trainees for a minimum of 2 years each in trauma related research laboratories. MDs are expected to have completed 2-3 years of clinical training in general surgery and to pursue an academic career in critical care, trauma surgery, or related specialties. PhD candidates will be selected based on documented interest or experience in trauma or inflammation research, immunology, or in related fields of study. In order to promote interdisciplinary team working skills, trainees will form 3 teams consisting of a PhD and MD trainee each. Each team partner will work on individual projects within related topics in trauma research. They will be encouraged to form close ties through joint attendance of conferences, seminars, and lectures. MD trainees will guide their PhD partner on clinical rounds to provide an in-depth understanding of actual clinical problems in the care for critically ill trauma patients. PhD trainees in turn will provide their MD partners with advice and assistance in the design of experiments and research strategies as well as exposure to new technologies. This training program will help trainees recognize the value of interdisciplinary team work and the benefit of vigorous information flow between closely collaborating clinical and basic scientists. This training approach and the excellent research infrastructure in the Harvard Longwood Area will help us achieve our overall goals, namely to develop a new breed of skilled researcher who can advance the field of trauma research and improve clinical trauma care.
Harvard Trauma Inflammation Training Program Despite remarkable progress in immunology and cell and molecular biology, inflammation, immune dysfunction, and organ failure have remained major causes of post-traumatic morbidity and mortality of critically injured patients. Inadequate information flow among clinical and basic researchers is a main reason why clinical improvements in post-traumatic outcome lag behind the rapidly increasing basic science knowledge. To improve this situation, novel science training approaches are required in order to promote interdisciplinary interactions of trauma researchers. This application seeks funding for a T32 training program to achieve this goal and to develop a cadre of future leaders in trauma researchers with the necessary interdisciplinary team working skills to advance the field and bring about the necessary transition that helps improve post-traumatic outcome. Led by a team of closely collaborating basic scientists and trauma surgeons in the Longwood Medical Area of Harvard University, this T32 program will pair MD and PhD trainees to form closely collaborating teams. MD and PhD team partners working on related research projects will interact on many levels to promote interdisciplinary exchange and information flow. PhD trainees will learn to see through their MD partners actual clinical problems in trauma care, while MD partners will learn how to work productively with their PhD partners to solve such clinical problems.
|Ledderose, Carola; Hefti, Marco M; Chen, Yu et al. (2016) Adenosine arrests breast cancer cell motility by A3 receptor stimulation. Purinergic Signal 12:673-685|
|Ledderose, Carola; Bao, Yi; Kondo, Yutaka et al. (2016) Purinergic Signaling and the Immune Response in Sepsis: A Review. Clin Ther 38:1054-65|
|Ledderose, Carola; Bao, Yi; Ledderose, Stephan et al. (2016) Mitochondrial Dysfunction, Depleted Purinergic Signaling, and Defective T Cell Vigilance and Immune Defense. J Infect Dis 213:456-64|
|Ledderose, Carola; Woehrle, Tobias; Ledderose, Stephan et al. (2016) Cutting off the power: inhibition of leukemia cell growth by pausing basal ATP release and P2X receptor signaling? Purinergic Signal 12:439-51|
|Qi, Baochang; Yu, Tiecheng; Wang, Chengxue et al. (2016) Shock wave-induced ATP release from osteosarcoma U2OS cells promotes cellular uptake and cytotoxicity of methotrexate. J Exp Clin Cancer Res 35:161|
|Chen, Yu; Bao, Yi; Zhang, Jingping et al. (2015) Inhibition of Neutrophils by Hypertonic Saline Involves Pannexin-1, CD39, CD73, and Other Ectonucleotidases. Shock 44:221-7|
|Ledderose, C; Bao, Y; Zhang, J et al. (2015) Novel method for real-time monitoring of ATP release reveals multiple phases of autocrine purinergic signalling during immune cell activation. Acta Physiol (Oxf) 213:334-45|
|Bao, Yi; Ledderose, Carola; Graf, Amelie F et al. (2015) mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis. J Cell Biol 210:1153-64|
|Ledderose, Carola; Bao, Yi; Lidicky, Markus et al. (2014) Mitochondria are gate-keepers of T cell function by producing the ATP that drives purinergic signaling. J Biol Chem 289:25936-45|