Mulligan | Biomedical and Molecular Sciences | School of Medicine

Lois Mulligan

Position(s)

Professor

Contact Info

mulligal@queensu.ca

613-533-6000 ext. 77475

Botterell Hall A315

Research Overview

Receptor tyrosine kinases link extracellular signals with intracellular pathways that cause cells to move, grow, proliferate or just survive. These roles are essential to normal development but can be hijacked in human cancers. My research group is interested in exploring the regulation of key cellular signals that contribute to both cancer and normal development that might also represent potential targets for future therapies. Our research is applying genetic, cell and molecular biology approaches to understand the functions and regulation of a cell surface protein of the receptor tyrosine kinase family, called RET, and its roles in the initiation, progression and spread of several challenging to manage human cancers.

We focus on dissecting the mechanisms regulating normal RET function and how changes in regulation can lead to cancer growth and spread. Understanding these processes will allow us to identify novel targets for future therapeutic interventions in RET-mediated cancers. Our current research is funded by the Canadian Institutes of Health Research.

Selected Recent Publications

RET isoforms contribute differentially to invasive processes in pancreatic ductal adenocarcinoma Lian EY, Hyndman BD, Moodley S, Maritan SM, Mulligan LM. Oncogene 2020, 39(41):6493-6510.

https://www.nature.com/articles/s41388-020-01448-z

Cells produce the RET protein in several different forms that have distinct roles in normal cells. In this study, we showed that one of these protein forms, called RET51, contributes to the movement and invasiveness of human pancreatic cancers. Our study identifies an important protein involved in cancer spread that could also be a therapeutic target in combating these tumours, and potentially a number of other challenging human cancers.

GGA3-mediated recycling of the RET receptor tyrosine kinase contributes to cell migration and invasion Crupi MJF, Maritan SM, Reyes-Alvarez E, Lian EY, Hyndman BD, Rekab AN, Moodley S, Antonescu CN, Mulligan LM. Oncogene 2020, 39(6):1361-1377.

https://www.nature.com/articles/s41388-019-1068-z

The movement of surface proteins into and within cells, and back to the cell membrane are important mechanisms regulating the extent and duration of signals. Here, we explored the sorting of RET protein isoforms for recycling or degradation and identify the molecules that interact with RET and promote these processes. These interactions are the key steps in controlling RET’s activity and, not only when, but where in the cell these signals are produced.

RET isoform-specific interaction with scaffold protein Ezrin promotes cell migration and chemotaxis in lung adenocarcinoma. Moodley S, Lian EY, Crupi MJF, Hyndman BD, Mulligan LM. Lung Cancer 2020, 142:123-131.

https://www.sciencedirect.com/science/article/pii/S0169500220303007?via%3Dihub

RET expression or mutation in human lung cancer can act as a tumour driver and promote metastasis. In this study, we showed that RET interacts with a key scaffold protein, Ezrin, to promote these processes, suggesting RET or Ezrin inhibition may have clinical value in these patients.

Full Publication list:

https://scholar.google.ca/citations?user=ARfODtAAAAAJ&hl=en

Current Mulligan Lab Members

Eduardo Reyes-Alvarez

PhD Candidate, DBMS, and Collaborative Cancer Program

Tim Walker

PhD Candidate PMM and Collaborative Cancer Program

Bryanna Thomson

MSc Candidate, DBMS, and Collaborative Cancer Program

Brandy Hyndman, PhD

Research Associate

Bronwen Barter

BSc Life Sciences

Korinna Chu

BSc Life Sciences

Courtney Ostromecki

BSc Life Sciences

Mina Tsakovska

MITACS Globalink student

Team

Research Overview

Selected Recent Publications

Current Mulligan Lab Members

Faculty