Liver Cancer: pre-Malignant Stiffening, Membrane Transduction, & Nuclear Rheology

 描述（由申请人提供）：PSOC Penn肝癌：恶性前硬化，膜转导和核流变学，癌症物理学的跨学科性质需要跨越多个边界的高效和有效的相互作用。我们选择重点关注原发性肝癌，主要是肝细胞癌（HCC），这是一种高度病态的肿瘤，是全球癌症死亡的第三大常见原因。HCC几乎总是发生在终末期肝纤维化（称为肝硬化）的背景下，新的原位测量肝硬度的方法正在成为HCC相对风险的有效预测因子。肝硬化患者的HCC发生率显著增加，但临床接受无疑将有助于-甚至需要-这里提出的研究。我们试图确定人类HCC与新鲜原代样本和肝组织力学之间关系的性质，细胞信号，以及核力学在DNA稳定性和肿瘤生长中的作用。宾夕法尼亚大学的五名临床医生经常看到患有肝病和肝癌的患者或样本，他们参与了拟议的PSOC Penn，因此影响诊所的机会是切实的。 在拟订这一贯穿各领域的建议时， 研究项目和2个核心，我们提出了一个多PI领导计划，以最好地代表专业知识和责任的不同领域：丹尼斯Discher博士（教授工程应用科学，格拉德团体物理，细胞和分子生物学）联系PI，管理核心负责人，项目PI-3核流变学：癌细胞系专业知识。Paul Janmey PhD（Prof. Physiology，Physics，and Bioengineering）PI of Project-1 Liver Mechanics：Cancer Cell Line Expertise. Rebecca威尔斯医学博士（医学、病理学和实验室医学副教授）核心1肝癌组织和模型的PI：肝病机制的专业知识。大卫E. Kaplan MD（医学助理教授，肝病学主任）Core-1肝癌组织和模型的共同PI：肝癌的临床专业知识。Andrea Liu PhD（Prof. Physics and Chemistry）Core-2 Theory的PI：统计物理建模的专业知识。宾夕法尼亚大学是一个单一的综合校园，所有参与中心的实验室都可以在5-10分钟内步行，宾夕法尼亚大学的医疗中心医院为大费城地区提供服务，是全国最大的肝病中心之一。为了将拟议的PSOC Penn纳入大学在癌症方面的广泛而深入的努力，PSOC的所有领导人和教职员工将成为Penn的Abramson癌症中心的成员（如果他们还没有）。艾布拉姆森癌症中心主任迟货车邓教授将担任试点项目-1的主要负责人，并将成为中心咨询委员会的主要成员。更广泛地说，PSOC Penn将通过教育和推广支持各种各样的计划，旨在建立一个充满活力的学生和研究员社区，他们体现了多学科方法来理解癌症的物理学，旨在改变下一代科学家，工程师和临床医生。

 DESCRIPTION (provided by applicant): PSOC Penn Liver Cancer: pre-Malignant Stiffening, Membrane Transduction, & Nuclear Rheology, The Transdisciplinary nature of Cancer Physics requires efficient and effective interactions across multiple boundaries. We have chosen to focus on primary liver cancer, predominantly hepatocellular carcinoma (HCC), which are highly morbid tumors that represent the third most common cause of cancer death worldwide. HCC almost always arises in the setting of end-stage liver fibrosis, termed cirrhosis, and new in situ methods of measuring liver stiffness are emerging as effective predictors of the relative risk of HCC. Patients with stiffer livers demonstrate dramatically increased rates of HCC, but clinical acceptance will no doubt be helped by - or even require - studies proposed here. We seek to determine the nature of the relationships between human HCC with fresh primary samples and the mechanics of liver tissues, the signals to cells, and the roles of nuclear mechanics in DNA stability and tumor growth. Five clinicians at Penn who regularly see patients or samples with liver disease and liver cancer are involved in the proposed PSOC Penn, and so the opportunities to impact the Clinic are tangible. In formulating this cross-cutting proposal with 3 Research Projects and 2 Cores, we propose a Multi-PI Leadership Plan to best represent the diverse areas of expertise and responsibility: Dennis Discher PhD (Prof. Eng'g Appl Sci, Grad Groups Physics, Cell & Molec Biol) Contact PI, Admin Core Lead, PI of Project-3 Nuclear Rheology: Cancer Cell line Expertise. Paul Janmey PhD (Prof. Physiology, Physics, and Bioengineering) PI of Project-1 Liver Mechanics: Cancer Cell line Expertise. Rebecca Wells MD (Assoc. Prof. Medicine, Pathology, and Laboratory Medicine) PI of Core-1 Liver Cancer Tissue and Models: Expertise in Mechanisms of Liver Disease. David E. Kaplan MD (Asst. Professor of Medicine, and Director of Hepatology) Co-PI of Core-1 Liver Cancer Tissue and Models: Clinical Expertise in Liver Cancer. Andrea Liu PhD (Prof. Physics and Chemistry) PI of Core-2 Theory: Expertise in Statistical Physics Modeling. Penn is a single, integrated Campus, with all of the labs involved in the Center walkable within 5-10 minutes, and Penn's Medical Center Hospital serves the greater Philadelphia area with one of the larger liver disease centers in the country. To integrate the proposed PSOC Penn within the University's broad and deep efforts in Cancer, all leaders and faculty members of the PSOC will become members of Penn's Abramson Cancer Center (if they are not already). The Director of the Abramson Cancer Center, Prof. Chi Van Dang, will be PI of Pilot Project-1 and will be a key member of the Center Advisory Committee. More broadly, the PSOC Penn will support through Education & Outreach a wide variety of programs that aim to build a vibrant community of students and fellows who embody the multidisciplinary approach to understanding the physics of cancer with an aim of transforming the next generation of scientists, engineers and clinicians.