Dr Alena Pance

I am a cellular and molecular biologist, interested in the mechanisms of cellular processes with the aim to understand how cells work in health and disease.

During my first degree in Venezuela, I became acutely aware of the major public health threat posed by infectious diseases, which sparked my interest in parasitology. I continued in this field during my MSc and early work in Venezuela, studying the host-parasite interaction in Chagas disease and the immune response to Malaria parasites. Then I became more interested in the molecular basis of biological processes and came to the UK where my fascination with transcriptional regulation started during my PhD at Cambridge. I studied the mechanisms that control the neuroendocrine differentiation pathway leading to the formation of neurones and exocrine cells. I continued my work on transcriptional regulation by investigating the control of NOS2 expression, as a fundamental part of the innate immune response and a potential tool for cancer therapy during my post-doctoral research position in the Faculty of Medicine at the University of Burgundy in France. I then obtained a European Marie Curie Research Fellowship, with which I came back to Cambridge to advance the research started during my PhD, until I took a permanent position at the Wellcome Sanger Institute where I became a Senior Staff Scientist. During this time, I designed a protocol to derive erythrocytes from stem cells in vitro to enable the study of human genetic traits and their role in malaria infection.

My main interest is the process and mechanisms of transcriptional regulation. Transcription is one of the key control points determining protein expression and therefore cellular fate and function.

With the advent of genome-wide approaches in research, variation and diversity have become a major focus, particularly because some variants are associated with disease and can give clues to identify causal genes and mechanisms of disease. However, most genomic variation is located in non-coding regions of the genome, implying an impact on regulatory mechanisms.

My interest in regulatory mechanisms includes the control of cellular pathways that determine cell differentiation and are critical for development, as well as cellular processes and function such as the inflammatory response, cardiac function and blood homeostasis and also the regulation of specific genes such as the inducible nitric oxide synthase, pivotal for the innate immune response and the histones, essential for cell proliferation and DNA repair. These processes are important in diseases such as cancer, rheumatoid arthritis, brugada syndrome an infectious diseases such as malaria.

My main work concerns the mechanisms by which the POU family of transcription factors control gene expression during development. This project uses stem cells to identify the regulatory landscape of the main POU factors in pluripotency and differentiation. Another branch of my research focuses on the regulation of histones by these factors thereby influencing cell proliferation and DNA repair. These studies aim to understand the processes of tumorigenesis and cancer progression.

I have a long-standing interest in tropical infectious diseases, particularly malaria as a major world-wide public health issue. Malaria parasites multiply in red blood cells, causing anaemia and more serious complications that can lead to cerebral malaria and death. Recent genome-wide association studies have identified a number of genetic traits that confer resistance to the infection but confirmation of these findings is hampered by erythrocytes being anucleated making genome editing impossible. To overcome this problem I developed an approach to differentiate erythrocytes from stem cells and examine parasite infection. This allows the generation of genetically modified as well as patient-specific erythrocytes by manipulating the stem cells or reprogramming them from patients with particular genetic traits. These in-vitro-generated cells are used for infection studies in order to understand the mechanisms by which human genetic variation can impact malaria infection.

I am also involved in the study of genomic variation in the promoter of voltage-gated sodium channels in the heart, in collaboration with Dr. Jackson in Cambridge. Some variants in the beta 3 subunit of these channels are associated to a heart condition called Brugada syndrome but the mechanisms involved are unknown.