Clare Rebbeck

Clare Clare Rebbeck
Senior Research Associate

 

Education

Ph.D., Imperial College London: Evolution of a transmissible cancer, 2006

MRes., Exeter University, 2003

BSc,  Biology, Exeter University, 2002

 

Research

I lead a small team focusing on breast cancer research. We are investigating a number of different questions using a combination of approaches involving imaging, low input RNA sequencing, lineage tracing and genetic manipulation. I also work on developing widely applicable tools and methodologies to help tackle these questions.

Tumor Dormancy

Many women who are diagnosed with breast cancer will not die from their primary disease. Instead, and sometimes many years after their initial diagnosis, they will develop spontaneous, rapidly advancing and often fatal metastasis.  It is thought that this metastasis develops from cancer cells that have lain dormant in distant niches, waiting for the signals to activate and divide. What keeps these cells in their dormant state is unknown, as are the signals that cause them to start rapidly dividing again. Is it the cells themselves that control their fate, or is it the local environment surrounding the lone cancer cell? Our work in this area is attempting to answer some of these questions. Using a sophisticated microscope, capable of imaging and sectioning simultaneously, we are able to image throughout an organ and retain the tissue for later analysis . This enables us to locate and visualize the environment of single cancer cells that are sitting in a dormant state, having left the primary tumor, and allows us to profile the gene expression of these cells and their local area. We are working on techniques to capture these cells and analyse their gene expression, allowing us to manipulate them in order for them to be either destroyed, or remain in their dormant state. The hope is that we will learn about how we can treat ALL the cells from a cancer.

Early stage breast cancer

Ductal carcinoma insitu (DCIS) is often referred to as early stage breast cancer.These abnormal cells are localized to the milk ducts, and technically still external to the body, they are therefore not considered as an invasive cancer. However this disease can progress, in approx 50% of cases, to invasive ductal carcinoma (IDC), where cells have broken out of the duct and begun to invade the breast tissue, developing into one of many subtypes of breast cancer. One of the major challenges of this disease is identifying what causes some women to develop IDC where as others do not, and how best to treat women diagnosed with DCIS to avoid over treatment. We are using a combination of laser capture microscopy, to isolate small,  specific areas of breast tissue with low input RNA seq to look for shared and distinct traits in this disease.

Tumor immune cells

The roles of  different cell types within a cancer is vast. Certain immune cells, such as T-cells and macrophages have been shown to play a fundamental role in the development of a primary tumor, and in its ability to metastasis. I am interested primarily in the role of macrophages and how the cancer cells are able to shift the state of these cells, from one which would potentially destroy the cancer cells, to one that instead promotes cancer growth. Being able to genetically manipulate these cells in vitro has long been a challenge, my work has allowed the infection of bone marrow derived macrophages with shRNA expressing virus, enabling the manipulation of target genes to track their contribution to the pro-tumor fate of these cells.

Tumor heterogeneity

Cancers are typically made up of a collection of different cell types, each one working with the others to perfect the ability for the cancer to grow and spread. How these different cells function is not 100% known. Do certain cells types always form the primary tumor, while others always go on to metastasis, and others still evade standard cancer drugs?  or is in a random collection of driver mutations that create tumor heterogeneity? I am interested in how we can use the existing heterogeneity within a tumor to learn about predispositions a cell might have, and how we can use this knowledge to develop new standard of care for cancer patients.