Dr Huan Cao

Biography

I have always been fascinated by how things work behind the scenes in nature.  It was after reading Natural Sciences at Cambridge and starting my PhD in immunology, also at Cambridge, that I found the love for a particular branch of immunology that involves sugar recognition.  During my PhD, I discovered the mechanism of evolution for a family of sugar recognising receptors know as Siglecs.  One particular Siglec, Siglec-15, was found through my work in the PhD, to be a key molecule that is highly specially expressed on leukaemia cells.  This fueled my passion for the research on sugar immune recognition because I saw the clinical implications and future benefits for patients beyond the academic endevour.

My adventures in sugar immune recognition reached a peak here in Aberdeen, where I discovered that the fundamental connection between that pathology of Sickle cell disease and malaria resistance lies in the recognition of a key sugar molecule, known as high mannose.  This discovery, published in Nature Communications, attracted much media attention.  The high mannose signal, for the first time, provides a fundamental understanding between immune recognition and clearance of old and damaged cells, excessive anaemia in sickle cell disease and the advantage of the sickle gene in combating malaria resistance.  This work is providing a foundation in future treatments of sickle cell disease, malaria infection and even novel ways to clear cancer cells.

Discovering this beauty of the inner workings of nature's and the potential in adapting these learnings to assist medical developments continues to fuel my explorations in this field.

External Memberships

British Society of Immunology

Prizes and Awards

1. IMS internal small grant award. £5,000.  From January 2019.  Filtration device for removing neoplastic and autoimmune cells from the blood stream.
2. Friends of Anchor. £9,000. From January 2019. Development of potential new diagnostics and therapies for sickle cell anaemia.
3. Wellcome Trust. Role of mannose receptor in recognition of dying cells by macrophages.  Period: 30/05/16 → 25/07/16.  Funder project reference: 201940/Z/16/Z.  Investigators: Barker, RN, Vickers, MA, Cao, H
4. Medical Research Scotland. £2,000. Construction and use of chimeric phagocytic receptors to reprogram macrophages to clear pathogenic cells by phagocytosis. Period: 22/05/17 → 17/07/17. Funder project reference: VAC-1057-2017.  Investigators: Vickers, MA, Cao, H
5. Travel Grant eFIS (2014)

Research Overview

My main interest is how sugar recognition influences immune responses.  This originated from my PhD in Cambridge with the discovery of leukaemic expression of a new sialic acid binding lectin known as Siglec-15.  This discovery now offers a “magic bullet” approach to treat the disease.  In Aberdeen, I employed plant lectins to discover the key “eat-me” sugar signals common to oxidized, malaria-infected and sickle cell disease red blood cells.  This signal triggers phagocytosis through the macrophage mannose receptor.  Serendipitously, by working with blood samples from patients who have had spleens removed, I discovered that the same sugar signals are the “aging” molecule for removal of end-of-life red blood cells.  These sugars are known as high mannoses and I look forward with great excitement to exploring their fascinating roles in malaria, cellular aging, sickle cell disease and cancer.

Research interests:

• Novel glycan-immune interactions between diseased, aging and damaged cells with the immune system
• Microvesicle oxidation and glycan profile
• Antibody and cellular based immune therapy
• Phage display
• Novel mechanisms in antigen presentation
• Sugar based technologies in tracking cellular trafficking and maturation of proteins.
• Phagocytosis mechanisms and receptor-ligand interactions

Disease model interests

• Diabetes and the role of red cells
• Immunotherapy of cancers
• Sickle cell disease
• Leukaemia (acute myeloid leukaemia and chronic lymphcytic leukaemia) and leukmic stem cells

Current Research

Currently I am working on the two aspects of the sickle-mannose axis.  The first is understanding the complexity of the underlying molecular basis built into the cytoskeleton of the cell for presenting mannose as an eat me signal.  The second is to develop commercialisation opportunities based on the principles of mannose as a novel eat me signal.  These include diagnostic tools for underlying medical issues and new therapeutic angles of treating solid tumours.

Past Research

My past research has primary been focused in three areas of glyco-immunology.  The first is in novel activating sugar Siglec molecules and the development of anti-leukaemia "magic bullet" drug.  The second is in recognition of aging cells.  Here, the focus was on red blood cells and mysenchymal stem cells.  The removal of aged mysenchymal stem cells during industrial production is a key bottleneck.  The third aspect of research is on how sickle cell disease and malaria resistance depend on a key sugar recognition mechanism.

Collaborations

Dr Louise Boyle (Senior Lecturer, Cambridge).  The role of glycan recognition in the antigen processing pathway of TAPBPR.  Publication: eLife 2017

Apollo (Pharmaceutical Company, Cambridge) and Cambridge Enterprise.  Sugar recognizing immune receptors.

Alexandra Stolzing (Professor of Regenerative Medicine, Loughborough University; Vice President of SENS Research Foundation, San Francisco).  Sugar recognition in mesenchymal stem cell aging.

Profs. Stuart Haslam and Anne Dell (Head of Department of Life Sciences, Imperial College, London).  Glycomics analysis of aging and diseased cells.

Prof Alex Rowe (University of Edinburgh).  Interaction between sugar recognition and malaria resistance.

Prof Marcel Jaspars (Head of Department of Chemistry, University of Aberdeen). Structural basis for recognition of aging and disease.