Clinicopathology of IGF2 loss of imprinting in colon neoplasia

简介（由申请人提供）：Cruz-Correa博士目前是波多黎各大学综合癌症中心（UPRCCC）的医学副教授和约翰霍普金斯大学（JHU）的医学访问助理教授。她在JHU获得了胃肠病学奖学金，并在约翰霍普金斯大学彭博公共卫生学院获得了临床研究博士学位，同时获得了K07 NCI导师奖。她的近期职业目标是过渡到一个独立的调查员有财政和时间资源，以完成她目前的假设在一个及时的时尚。她的长期目标是成为胃肠道肿瘤学领域的领导者，重点是表观遗传学，临床结果和预防。具体来说，Cruz-Correa博士设想了一个转化胃肠道研究机构，包括：(1)一个基础实验室单位，(2)一个临床研究单位，共同评估多种假设，依次阐明胃肠道致癌机制。UPRCCC完全致力于发展Cruz-Correa博士的职业生涯，并将提供所有必要的人员，实验室，临床资源以及成功完成这项调查所需的保护时间。该奖项将使她能够继续发展必要的技能，在她目前的导师和共同研究者的支持下，在临床研究中取得成功的独立职业生涯，Francis Giardiello博士，Andrew Feinberg博士（约翰霍普金斯大学），Steven Wexner博士（佛罗里达州克利夫兰诊所）和reynolds Lopez博士（UPRCCC）。

DESCRIPTION (provided by applicant): Dr. Cruz-Correa is currently an Associate Professor of Medicine at the University of Puerto Rico Comprehensive Cancer Center (UPRCCC) and visiting Assistant Professor of Medicine at Johns Hopkins University (JHU). She completed a gastroenterology fellowship at JHU and finished a doctorate degree in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health, while completing her current K07 NCI Mentored Award. Her immediate career goals are to transition into an independent investigator having the financial and time resources to complete her current hypothesis in a timely fashion. Her long-term objectives are to become a leader in the field of gastrointestinal oncology with emphasis in epigenetics, clinical outcomes and prevention. Specifically, Dr. Cruz-Correa envisions a translational gastrointestinal research institute integrated by: (1) a basic laboratory unit, and (2) a clinical research unit, working together evaluating multiple hypotheses to sequentially elucidate mechanisms of gastrointestinal carcinogenesis. The UPRCCC is fully committed to the development of Dr. Cruz-Correa's career, and will provide all the needed personnel, laboratory, clinical resources as well as the protected time required for successful completion of this investigation. This award will enable her to continue to develop the necessary skills for a successful independent career in clinical research with the support of her current mentors and co-investigators, Dr. Francis Giardiello, Dr. Andrew Feinberg (Johns Hopkins University), Dr. Steven Wexner (Cleveland Clinic Florida), and Dr. Reynold Lopez (UPRCCC). This project will test the hypothesis that abnormal imprinting of the IGF2 gene is a biomarker for colorectal cancer (CRC) predisposition, with a diffuse tissue distribution, which exerts its increased risk via the IGF axis, resulting in specific pathological and molecular characteristics and a unique CRC phenotype. Loss of imprinting (LOI) of IGF2 is an independent risk factor for CRC, but the underlying carcinogenic mechanisms remain unclear. LOI of IGF2 is present in the peripheral blood lymphocytes (PBL) of patients with CRC and is not associated with common environmental exposures. This investigation will determine the clinicopathological impact of LOI of IGF2 and delineate the underlying molecular mechanisms of the IGF2 system in CRC patients using a feasible cross-sectional and matched case-control design. Specifically, it will evaluate the association of LOI of IGF2 with the IGF2 peptide, proliferation index, apoptosis index and micro-vascular density in CRC patients. It will also examine the association between LOI and rectal cancer recurrence. LOI of IGF2 has potential as a new biomarker for colorectal cancer predisposition, and may change our current risk-stratification, screening, and surveillance colorectal cancer paradigms.