Programme ManagementParticipating Investigators and Research AreasPhD Scholars

Meet the PhD Scholars

The PhD Scholars Programme in Cancer Biology at University College Cork currently has ten PhD students working toward PhDs in cancer biology.  Please scroll down to read about the research interests of each of our PhD Scholars. 

My research deals with the role of NF-kB in Toll-Like Receptor (TLR) signalling. The NF-kB pathway has been one of the most intensely studied biochemical pathways over the last decade; however, our understanding of the pathological perturbations of NF- κB signalling is limited.  I am interested in looking at the regulatory role of NF-kB interacting proteins, specifically the promyelocytic leukaemia protein (PML).

The requirement of cholesterol and lipids in cancer progression is well-characterised. The SREBP pathway regulates expression of genes involved in the de novo synthesis of these molecules. A key component of this pathway is the SREBP cleavage activating protein (SCAP), which regulates proteolytic cleavage and activation of the SREBPs. My research focuses on the role of the SREBP pathway in cancer cell proliferation, with a major focus on further characterisation of SCAP.

 

My research interest in general is cell signalling and more particularly how cell surface receptors can contribute to tumorigenesis. My PhD project focuses on the p75 neurotrophin receptor, whose signalling and intra-membrane proteolysis have been found to be crucial for glioblastoma cell motility and invasiveness.

Publications

Mosesson Y, Chetrit D, Schley L, Berghoff J, Ziv T, Carvalho S, Milanezi F, Admon A, Schmitt F, Ehrlich M, Yarden Y (2009) Monoubiquitinylation regulates endosomal localization of Lst2, a negative regulator of EGF receptor signaling. Dev Cell 16, 687-698

Koren-Michowitz M, Hardan I, Berghoff J, Yshoev G, Amariglio N, Rechavi G, Nagler A, Trakhtenbrot L (2007) Chromosome 13q deletion and IgH abnormalities may be both masked by near-tetraploidy in a high proportion of multiple myeloma patients: a combined morphology and I-FISH analysis. Cancer Lett 255, 307-314  

 

 

My present research interests revolve around optimising the immune effector function within the tumour micro-environment, principally by abrogating the immuno-suppressive contribution of regulatory T cells. The main strategy for achieving this goal is the development of a novel therapeutic; a ligand-directed viral platform capable of mediating cell-specific RNA interference.

The NADPH oxidase (Nox) family of enzymes generate reactive oxygen species (ROS) which have been shown to be involved in the regulation of various intracellular signalling pathways. Due to their different locations, both within cells and within tissues, this group of proteins affect many cellular functions including growth, motility and cell survival. My research is centered on the role of Nox-driven cell survival signalling in acute myeloid leukemia (AML).

The focus of my research is how HRG-1, a heme-binding protein identified in C. elegans and separately identified in IGF-1R transformed cells as a vacuolar (H+) ATPase-associated protein, is involved in cancer cell progression.

My research focuses on the differential roles of the non-muscle actinins, isoforms 1 and 4.   Discrepancies exist with regard to the roles that these isoforms have in cancer development and progression. Both non-muscle isoforms have been reported to act as tumour promoters and suppressors in different cancer types. In particular, my work examines the localisation and molecular interactions of actinin 1 and 4. The identification and characterisation of actinin-interacting proteins should better aid our understanding of the molecular mechanisms that underlie non-muscle actinin function, leading to cell migration and metastasis.

Several of the signalling pathways underlying cancer pathogenesis are also involved in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Previous work in our lab and others has shown that Akt/PTEN signal transduction is altered in neurodegeneration. One gene associated within this signalling axis is PTEN-induced kinase 1 (PINK1).   Mutations in PINK1 are the second most frequent cause of autosomal recessive Parkinson’s disease. I am interested in the role of this protective kinase and its signalling partners in cancer biology and pathogenesis.

Pregnancy specific glycoproteins (PSGs) are a multi-gene family of proteins secreted by the foetus into the maternal bloodstream during pregnancy. They are the highest foetally produced proteins in the maternal blood at the end of pregnancy. Widely reported to be immuno-modulatory, their potential roles in angiogenesis and vascular remodelling has been investigated more recently. The aim of my PhD studies is to understand and elucidate further the biology of the human PSGs through the identification of a receptor for these glycoproteins.   I would also like to determine if their immuno-modulatory and hypothesized angiogenic properties can be harnessed or modified to therapeutic benefit in models of vascular dysfunction or disease. Elucidation of the molecular mechanism underlying PSG function may also lead to a greater understanding of the way cancers utilize angiogenesis and immune modification to survive.

My thesis project is focused on the post-translation regulation, processing and degradation of the enzyme L-histidine decarboxylase (HDC), the single enzyme responsible for histamine production in mammals.  Increased expression of HDC and histamine has been associated with different cancer cell types within the context of proliferation, wound repair, tumour growth, angiogenesis and even metastasis. I am interested in studying HDC’s role in the development of gastric cancer in combination with Helicobacter pylori infection, which has been linked to ulcers, MALT lymphoma and gastric cancer.