Pilot Project Awardees

2018-2019 Awards

Mariangela Amenduni, PhD

Amenduni Headshot

Associate Research Scientist, Internal Medicine: Digestive Diseases
Project Title: Use of hiPSCs to study the function of CFTR mutations in cholangiocyte innate immunity

About 2000 mutations have been identified in CFTR and multiple studies have been done to establish a correlation between the CFTR genotype and CF disease phenotype, however this relationship is not well understood. Understanding how CFTR mutations translate to altered synthesis or function of CFTR protein in human cholangiocytes and how the genetic defects are connected to the biliary epithelial innate immunity response, will be useful to personalize the therapeutic approach to the patient. In this project we will address these unsolved questions using iPSCs (induced pluripotent stem cells) technology to generate cholangiocytes from patients bearing CFTR mutations belonging to different functional classes.

Venkata Boddupalli, PhD


Associate Research Scientist, Internal Medicine: Digestive Diseases
Project Title: Delineating the role tissue resident T cells in mediating immunopathology of PSC-IBD

We aim to elucidate the underlying role of tissue resident memory T cells (TRM) in immunopathogenesis of PSC and the mechanistic basis for the coexistence of IBD with PSC. We are using Kaede-PSC photoconvertible transgenic mice model to address the role of gut resident TRM cells in causing PSC and liver tissue pathology. We intend to capture and characterize pathogenic T cell clones that have homed from GI tract to liver using Kaede-PSC mouse model. These mice models will improve our understanding of the role played by TRM cells in cholangiopathies. Also, comparing these observations obtained from Kaede-PSC mouse model with human clinical data will further expand our view about PSC biology.

Xinshou Ouyang, PhD


Assistant Professor, Internal Medicine: Digestive Diseases
Project Title: RNA methylation landscaping of gene regulation in macrophage-mediated inflammation in NASH

N6-methyladenosine (m6A) is the abundant internal modifications in many sites of messenger RNA, modulated by adenosine methyltransferases (‘writers’), demethylases (‘erasers’) and RNA binding proteins (‘readers’) to shape the cellular 'epitranscriptome’. m6A thus functionally influences all fundamental aspects of mRNA metabolism, mainly mRNA stability. However, its physiological function in immune cells is yet not fully understood. Mechanisms for non-alcoholic steatohepatitis (NASH) development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. The goal of this proposed research is to delineate the signaling events of m6A directed macrophages in the existence of redox status and chronic inflammation in NASH.

Gregory Tietjen, PhD


Assistant Professor, Surgery: Transplant
Project Title: Personalized diagnostic profiling of donor livers during ex vivo perfusion

A severe shortage of viable livers and the declining health of the donor population represent the two most significant challenges facing clinical liver transplantation today. These challenges are exacerbated by the lack of robust diagnostic tools capable of providing a clear assessment of donor liver viability. Historically, the decision to transplant a given organ is highly subjective, which can lead to systemic inefficiencies, the potential for discard of usable organs and increased waitlist mortality. Ex vivo normothermic perfusion of deceased donor livers has emerged as a platform that can enable more sophisticated assessment of organ viability and even provide an opportunity to repair marginal organs to make them suitable for transplantation. In this project, we aim to develop quantitative diagnostic imaging tools for use during ex vivo normothermic liver perfusion to provide personalized assessments of each donor liver prior to transplantation. We believe this work has the potential to improve utilization of marginal liver allografts and thereby reduce waitlist mortality. 

Steven (Siyuan) Wang, PhD


Assistant Professor, Genetics and Cell Biology
Project Title: Imaging-based 3D genomics and transcriptomics in aging liver

Aging poses a major risk for many liver diseases. At the cellular level, the occurrence and accumulation of senescent cells is a main characteristic of aging liver. The molecular mechanism governing cellular senescence and its downstream effects have been studied relatively extensively in cell culture systems, but a detailed picture of the native molecular compositions and molecular/cellular spatial organizations of senescent cells in an aging liver remains elusive. In this study, we aim to profile single-cell transcriptome and to trace chromatin organization in the native liver tissue context through the aging process, with our state-of-the-art imaging-based in-situ transcriptomics and genomics technologies. The study will reveal the in situ molecular mechanism underlying cellular senescence and aging, as well as the interactions between senescent cells and their microenvironment, at different ages.

For information on completed Pilot Project Awards, please click below.