Northwestern University Feinberg School of Medicine

Comprehensive Transplant Center

PPG: Integrating Mechanistic Insights from Diverse Models to Prevent Reactivation of CMV following Transplantation

Cytomegalovirus (CMV) is a member of the herpesvirus family that latently infects the majority of the population.  Reactivation of latent CMV causes significant infectious complications in immunocompromised hosts, including recipients of solid organ transplants.  Current anti-viral therapies are associated with toxicity and development of resistant strains.  Furthermore, these therapies target replication of the virus after reactivation has occurred.  The goal of this project is to better understand the molecular mechanisms that control repression of viral gene expression in latency, and to identify factors that lead to activation of viral gene expression in response to transplantation.  This knowledge may lead to the development of novel therapies that prevent reactivation, rather than treating it after it has occurred.  There are two overall themes: 1) that epigenetic factors control both repression of viral gene expression in latency and activation of gene expression in reactivation; 2) that an inflammatory immune response triggers reprogramming of viral chromatin to activate viral gene expression in transplant recipients.

This program project is comprised of three sub-projects and three cores.  In Project 1, Dr. Abecassis will investigate molecular pathways leading to reactivation of murine CMV (MCMV) using both in vivo models that closely mimic the clinical setting of reactivation in immunocompromised transplant recipients and recently developed in vitro models. In Project 2, Dr. Hummel will investigate epigenetic factors that control latency and reactivation of HCMV in hematopoietic progenitor cells, which are sites of latency in vivo.  In Project 3, Dr. Luo will investigate MCMV infection, latency and reactivation in transplantation, specifically using donor-specific transplant tolerance. 

Projects and Cores 

Faculty Associated with the Program Project: Integrating Mechanistic Insights from Diverse Models to Prevent Reactivation of CMV following Transplantation
Principle Investigator Michael Abecassis, MD, MBA
Co-Investigator Yashpal Kanwar, MD, PhD
Co-Investigator Neil Kelleher, PhD
Co-Investigator Suchitra Swaminathan, PhD
Co-Investigator Paul Thomas, PhD
Co-InvestigatorLihui Zhao, PhD
Co-InvestigatorXue Feng Liu, PhD
Co-InvestigatorXiaomin Zhang, MD
Subcontract PI Scott Terhune, PhD

Recent News

Thank you to all who participated in our second annual CMV P01 Symposium for Cytomegalovirus Latency and Reactivation on Tuesday, September 19th, 2017. 

Congratulations to Dr. Michael Abecassis and colleagues for the recently awarded P01 grant issued by the National Institute of Health (NIH) titled, Integrating Mechanistic Insights from Diverse Models to Prevent Reactivation of CMV following Transplantation!