Professor Randall Johnson

I received a Bachelor of Science in Molecular Biology and a Bachelor of Arts in Swedish Language and Literature concurrently in 1983 from the University of Washington, in Seattle.  Having resolved to choose science over literature, I worked for a couple of years as a research technician for Dr. Don Pious at the UW, on a project concerned with the genetics of the human major histocompatibility complex. I then went to Harvard to do my doctoral work with Prof. Bruce Spiegelman, where we were involved in the early days of gene targeting in embryonic stem cells; and I knocked out the c-fos and c-jun proto-oncogenes, amongst others, while receiving a Ph.D. in Genetics.  I did my post-doctoral work as a Jane Coffin Childs Fellow with Prof. Doug Hanahan when he was at UC San Francisco, working on the role of angiogenesis in transgenic tumor models.  I began my career as a group leader in the Dept. of Biology at the University of California, San Diego. There, our lab began our study of hypoxia and its effects on tumorigenesis and physiology, continuing to use knockout and other genetic models.  In 2011, I came to Cambridge and the Dept. of PDN as a Wellcome Trust Principal Research Fellow. In 2012 I became an associated member of the Department of Cell and Molecular Biology of the Karolinska Institute, in Stockholm, Sweden. In 2015 I became a member of the Nobel Assembly at the Karolinska Institute.

We work on how the body responds to hypoxia, or low levels of tissue oxygen.  This is relevant to a number of diseases, including cancer, and the laboratory is interested in hypoxic response in disease as well as in normal physiology.

• The response to hypoxia acts in significant part through the Hypoxia Inducible Factor, or HIF.  The actions of this transcription factor are evident in almost all forms of cancer, but HIF is also present in other disease states.  Further, many aspects of normal physiological response include activation of HIF: HIF expression is seen in normal embryonic development, it is seen whenever wound healing or inflammation occur, and is essential for adjustment to high altitude or whenever the organism experiences a lower than normal level of oxygen.
• Cancer: our work has for many years focussed on how malignant cells and the tissues that surround and infiltrate them react to oxygen levels.  The levels of oxygen found vary tremendously both from cancer to cancer, and within individual tumors.  One of the key findings from our recent work has been that each cell type found within tumors utilizes the HIF response differently; the malignant cells, tumor-associated fibroblasts, myeloid cells, endothelial cells and lymphoid cells all have different spectra of response via HIF, and these differences impact how tumors grow, survive and, ultimately, metastasize.
• Inflammation, infection and immunity: We have investigated how T cells and macrophages utilize hypoxic response to allow immune response.  We are actively investigating this in terms of models of infection, inflammation, and immunological response to cancer; and we are also asking how myeloid/lymphoid interactions are affected by the response to oxygenation.
• Physiology: a critical aspect of ventilatory control is the normative response of the carotid body and other tissues to the organisms overall oxygenation.  This response in turn can affect various aspects of homeostasis, including pulmonary vascular tension and even systemic blood pressure.  We have found that this control is highly related to the function of HIF and hypoxic response, in a way that is tightly controlled by complex interactions amongst tissue types.