Jack Stenning

Defining Estrogen Receptor Binding and Response Determinants at Single-Cell Resolution

About me

I started my undergraduate study in 2015, studying Biochemistry at the University of Leeds. I studied under Dr Edwin Chen for my undergraduate project, utilising CRISPRi to modulate zinc homeostasis in myeloproliferative neoplasms. My time in the lab left me wanting to expand my experience in biological research. In 2018, I moved to Cambridge to work for the BRC Phenotyping Hub at Addenbrooke’s hospital. My experience at the Hub provided me with a cross-sectional insight into all of the workings of a flow cytometry facility and its users’ research. That experience taught me my passion was the academic research of cancer biology.  I therefore, moved again to join Dr Walid Khaled’s lab in the Department of Pharmacology for the University of Cambridge as a Research Assistant. My role was to lead the processing of samples from Breast Cancer Now Tissue Bank to generate data for the Human Breast Cell Atlas project. The scale of Cell Atlas as an international collaborative project and the enormous responsibility was highly rewarding solidified my drive to work in breast cancer research. As a result, I was delighted to return to Yorkshire in October 2021 to begin my PhD studying the estrogen receptor (ER). I hope that my work will provide new insights into this field of study and help us understand this disease to one day overcome it.

My research

Female breast cancer is the most commonly diagnosed cancer globally and leads to the deaths of tens of thousands of people in the UK alone each year. Of these cases, the majority (~65-75%) are considered ER-positive, showing that the ER protein has a significant role in breast cancer progression. Although much work is being done to understand how ER carries out this role, many of the mechanisms involved in this process are still unknown. A significant confounding variable contributing to this is that ER binding and response are highly heterogeneous across cell types within a single patient and individuals. To overcome this variable, I believe researchers must take up new approaches to characterise nuclear receptor binding in situ; I aim to do so by utilising novel next-generation sequencing methods and applying them to heterogeneous populations of cells. I intend to use ER itself to map the binding profile of the nuclear receptor on a genome-wide scale. These data can then be collected at single-cell resolution to directly couple transcription factor binding to cell identity. Through this method, I plan to show how ER binding response has contributed to the cell state at the time of sequencing. Therefore, when sequencing patient samples, I will be able to generate clinically relevant information about the role of ER within that patient. Furthermore, after treatment, it is possible to change the components of the growth medium to assess how ER binding and response is differentially regulated in these conditions. By applying this technology to many patient and volunteer samples, I aim to define the changes in the ER binding heterogeneity between healthy and malignant breast tissue. These changes underpin the development of healthy breast tissue and processes that lead to cancer; I hope we can find new ways to prevent disease by understanding these changes.


LinkedIn: https://www.linkedin.com/in/jack-philip-stenning/

Twitter: https://twitter.com/JackStenning6