Terence Rabbitts

Last updated
Terry Rabbitts
Terence-rabbitts-600x600.jpg
Alma mater University of East Anglia
National Institute for Medical Research
Awards Colworth Medal (1981)
FRS (1987)
CIBA medal (1993)

FMedSci (1998)

Clotten Foundation Award (2015)

FACCR (2022)
FRCP (2024)
Scientific career
FieldsMolecular Biology & Molecular Immunology
Institutions The Institute of Cancer Research
Weatherall Institute of Molecular Medicine
Leeds Institute of Molecular Medicine
MRC Laboratory of Molecular Biology
Website www.icr.ac.uk/our-research/researchers-and-teams/professor-terence-rabbitts www.orbitdiscovery.com

Terence Howard Rabbitts is Professor of Molecular Immunology at the Institute of Cancer Research, London. [1]

Contents

Education

He was educated at John Ruskin Grammar School, the University of East Anglia where he graduated with a BSc with first class honours in Biological Sciences, and subsequently completed his PhD at the National Institute for Medical Research, Mill Hill, London. [2]

Career & Research

Terry Rabbitts obtained a BSc at the School of Biological Sciences, University of East Anglia where he studied molecular genetics, obtaining a First Class Honours. He obtained a PhD at the National Institute for Medical Research, Mill Hill (NIMR) supervised by Thomas Work (at NIMR) and by Ken Murray (at the University of Edinburgh) on mitochondrial nucleic acid homogeneity. At NIMR, he became interested in molecular immunology from Peter Medawar's work on immune tolerance. He worked as a post-doctoral fellow in Cesar Milstein's group at the MRC Laboratory of Molecular Biology (LMB) in Cambridge from 1973. He became a group leader at LMB in 1978 and succeeded Fred Sanger as joint Head of the Division of Protein and Nucleic Acid Chemistry at LMB in 1998, together with César Milstein and later with Sir Greg Winter. He was Director of the Leeds Institute of Molecular Medicine in 2007-2012 and moved to the University of Oxford to become Professor of Molecular Immunology at the MRC Weatherall Institute of Molecular Medicine. He has been Professor of Molecular Immunology in the Division of Cancer Therapeutics at the Institute of Cancer Research, London since 2020.

His contributions in biotechnology include chairing the Scientific Advisory Board of Cambridge Antibody Technology from its launch until its IPO, of Quadrant Healthcare until its acquisition by Elan, and of Kymab until its acquisition by Sanofi. He was an SAB member of Domantis until acquisition by GSK, and a Non-Executive Board member of Aptuscan until its acquisition by Avacta. He is a co-founder of three start-up companies, Orbit Discovery, Quadrucept Bio and Kodiform Therapeutics.

His research has focussed on antibody and T cell receptor gene diversity, gene rearrangement and aberrant rearrangement of chromosomes (chromosomal translocations) in cancer. He pioneered the method of cDNA cloning, an approach universally used in bioscience and biotechnology, and elucidated the organization, diversity and rearrangement of human antibody genes, which defined the building blocks for construction of therapeutic antibody repertoires. He also pioneered chimaeric antibodies (with the late Michael Neuberger). He discovered the LMO and HOX11 chromosomal translocation oncogene families in T cell leukaemia and the first fusion gene in a solid tumour. He developed the first knock-in gene, now a widely employed approach in gene targeting and gene editing. He also pioneered the design of intracellular antibody single domain fragments (iDAbs) and established approaches to develop these macromolecules (these he called macrodrugs) with warheads to induce cellular phenotypes). He has developed methods to select chemical compound surrogates using single domain intracellular antibody fragments as competitors. These methods have resulted in drug leads for the previously considered undruggable RAS proteins and the hard-to-drug translocation proteins LMO2. His methods allow the use of intracellular antibody fragments to select chemical compounds that bind to disordered proteins within cells. Since 2020, his laboratory work has been focussed on developing methods to deliver intracellular antibody fragments into cells as drugs per se and targeting fusion proteins made from chromosomal translocations.

Awards and honours

He is a Fellow of the Royal Society, a Founder Fellow of the Academy of Medical Sciences, an EMBO Member and a Fellow of the American Association for Cancer Research Academy. He has been awarded the Colworth Medal, the CIBA prize and the Clotten Foundation Prize in recognition for his work on the diversity and rearrangement of human antibody genes, and on chromosomal translocation genes in cancer aetiology. He was elected as an Honorary Fellow of the Royal College of Physicians in 2024 for applying molecular biology to human disease and the development of new therapeutics.

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">Oncogene</span> Gene that has the potential to cause cancer

An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

<span class="mw-page-title-main">Chromosomal translocation</span> Phenomenon that results in unusual rearrangement of chromosomes

In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal, and Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" and blends together homogeneously.

<span class="mw-page-title-main">Acute lymphoblastic leukemia</span> Blood cancer characterised by overproduction of lymphoblasts

Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.

<span class="mw-page-title-main">Gregory Winter</span> English biochemist (born 1951)

Sir Gregory Paul Winter is a Nobel Prize-winning English molecular biologist best known for his work on the therapeutic use of monoclonal antibodies. His research career has been based almost entirely at the MRC Laboratory of Molecular Biology and the MRC Centre for Protein Engineering, in Cambridge, England.

V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system.

<span class="mw-page-title-main">MRC Laboratory of Molecular Biology</span> Research institute in Cambridge, England

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory at the forefront of scientific discovery, dedicated to improving the understanding of key biological processes at atomic, molecular and cellular levels using multidisciplinary methods, with a focus on using this knowledge to address key issues in human health.

Alan James Munro is a British immunologist and entrepreneur who served as the Master of Christ's College, Cambridge (1995–2002).

<span class="mw-page-title-main">Alexander Varshavsky</span>

Alexander J. Varshavsky is a Russian-American biochemist and geneticist. He works at the California Institute of Technology (Caltech) as the Morgan Professor of Biology. Varshavsky left Russia in 1977, emigrating to United States.

Michael Samuel Neuberger FRS FMedSci was a British biochemist and immunologist.

<span class="mw-page-title-main">Cambridge Biomedical Campus</span> Science park in Cambridge, UK

The Cambridge Biomedical Campus is the largest centre of medical research and health science in Europe. The site is located at the southern end of Hills Road in Cambridge, England.

Suzanne Cory is an Australian molecular biologist. She has worked on the genetics of the immune system and cancer and has lobbied her country to invest in science. She is married to fellow scientist Jerry Adams, also a WEHI scientist.

A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for cancer immunotherapy, drug delivery, and Alzheimer's disease.

<span class="mw-page-title-main">RNA-binding protein EWS</span> Human protein and coding gene

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. It is one of 3 proteins in the FET protein family.

The Sir William Dunn School of Pathology is a department within the University of Oxford. Its research programme includes the cellular and molecular biology of pathogens, the immune response, cancer and cardiovascular disease. It teaches undergraduate and graduate courses in the medical sciences.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Ashok Venkitaraman is a British cancer researcher of Indian origin. He is the Director of the Cancer Science Institute of Singapore, a Distinguished Professor of Medicine at the National University of Singapore, and Program Director at A*STAR, Singapore. From 1998 to 2020, he was the inaugural holder of the Ursula Zoellner Professorship of Cancer Research at the University of Cambridge, a Professorial Fellow at Pembroke College, Cambridge, and from 2006 to 2019, was the Director of the Medical Research Council Cancer Unit.

<span class="mw-page-title-main">Ketan J. Patel</span>

Ketan Jayakrishna Patel is a British–Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).

<span class="mw-page-title-main">Weatherall Institute of Molecular Medicine</span>

The MRC Weatherall Institute of Molecular Medicine at the University of Oxford is a research institute located at the John Radcliffe Hospital in Oxford. Founded in 1989 by Sir David Weatherall, the institute focuses on furthering our understanding of clinical medicine at a molecular level. It was one of the first institutes of its kind in the world to be dedicated to research in this area.

References

  1. "Professor Terence Rabbitts - the Institute of Cancer Research, London".
  2. "RABBITTS, Prof. Terence Howard" . Who's Who . A & C Black.(Subscription or UK public library membership required.)