The long-term objective of this proposal is to foster the scientific development of the candidate to enable her to become an independent clinical investigator. The components of her career development program are formal coursework, intense mentoring and performing a cohort study of the relationship between iron metabolism and risk of infection after orthotopic liver transplantation (OLT). This proposal will use two major teaching hospitals of the rich research environment of Tufts University School of Medicine: Tufts-New England Medical Center (now known as Tufts Medical Center) and Lahey Clinic. Under the mentorship of Dr. David Snydman, an expert in transplant infectious diseases and epidemiology, and Dr. Tomas Ganz, an expert in iron metabolism, the candidate will be guided towards an independent research career. Ultimate and immediate career goals are, respectively, to focus on the prevention, early detection and management of infections in immunocompromised persons, and to begin to examine the complex relationship between host iron metabolism and infections in OLT recipients. Infection is a common and potentially lethal complication of OLT. Iron is a universal nutrient for nearly all pathogens. The iron hormone, hepcidin, is thought to be the central regulator of human iron metabolism, and consequently, controls host serum iron levels. The central hypothesis is that hosts who are less able to appropriately regulate serum iron levels are at greater risk for infectious complications after OLT. Therefore, increased levels of serum iron markers will be associated with an increased risk of invasive infections among OLT patients after adjusting for other clinical factors.
The specific aims of this proposal are:
Aim 1 : To determine whether the dysregulation of iron metabolism is an independent risk factor for the development of infection in a prospectively assembled cohort of OLT recipients.
Aim 2 : To understand how the hepcidin-iron axis functions in a prospectively assembled cohort of OLT recipients in the presence and absence of infection. The successful completion of this study will therefore have a significant positive impact on the understanding of iron metabolism after OLT and the role of iron as a modifiable risk factor for infection in OLT recipients.
Infections after liver transplantation are common and potentially lethal complications. We will study the relationship between iron metabolism and blood iron levels and the risk of infection after liver transplantation. This research can help develop new ways to detect and treat infections in this vulnerable population.
|Alraddadi, Basem; Nierenberg, Natalie E; Price, Lori Lyn et al. (2016) Characteristics and outcomes of neutropenia after orthotopic liver transplantation. Liver Transpl 22:217-25|
|Chow, Jennifer K; Werner, Barbara G; Ruthazer, Robin et al. (2010) Increased serum iron levels and infectious complications after liver transplantation. Clin Infect Dis 51:e16-23|