Dr Kalwant S Authi PhD
Senior Lecturer in Physiology
Physiology Programme Advisor
King's College London
150 Stamford St.
London SE1 9NH
Dr Authi obtained a B.Sc. honours in Medical Biochemistry (1976) from the University of Birmingham, a M.Sc. in Medicinal Chemistry (1977) from University of Loughborough and a Ph.D. in Biochemical Pharmacology (1981) also from the University of Loughborough. Dr Authi carried out postdoctoral research at the Royal College of Surgeons of England in London (1981-1990) and served as Lecturer and Senior Lecturer at the Thrombosis Research Institute in London from 1990-2001. He moved to King’s College London in 2001 and is currently a senior lecturer in physiology and programme advisor in physiology for undergraduates and intercalating medical, dental and veterinary students.
Dr Authi is a member of the Biochemical Society of Great Britain, the British Society for Haemostasis and Thrombosis, the International Society for Thrombosis and Haemostasis, the South Asian Society for Atheroscloresis and Thrombosis and the Physiological Society of Great Britain.
Dr Authi's major interest is to understand the Ca2+ signalling mechanisms in human platelets and to investigate potential new anti-thrombotic targets. Platelet activation plays a major role in haemostasis and in pathological events leading to myocardial infarction or stroke. Current treatment options for stroke in particular are very limited. Ca2+ elevation in the platelet cytosol is a major signal important in the expression of platelet functions and currently mechanisms involved in Ca2+ entry are not well understood. The entry pathways include store dependent and independent routes in addition to Ca2+ entry via the P2X1 receptor.
All may lead to the development of novel therapeutic strategies limiting platelet activation. Recent studies have established the protein STIM1 as the sensor of intracellular Ca2+ stores that stimulates the plasma membrane Ca2+ entry channel when stores are depleted following platelet stimulation. Orai1 has been confirmed as the store operated Ca2+ entry channel. Members of the TRP family of entry channels have also been shown to be present in platelets but their roles require further investigation.
Dr Authi’s recent work focussed on the elucidation of the role of the TRP family of cation entry channels in mediating Ca2+ entry in platelets and megakaryocytic cells. Key achievements include the first demonstration that TRPC6 is the major non-store operated cation entry channel present in platelets, that thrombin and diacylglycerol lead to stimulation of TRPC6 and that it is a substrate for cAMP-dependent protein kinase. Dr Authi’s work suggest that TRPC1 is not essential for store operated Ca2+ entry in human platelets. Currently the role of STIM1 in platelet activation is being elucidated. STIM1 is known to be present primarily in the intracellular store membrane but a small proportion is also found in the plasma membrane and indeed its initial discovery was as a plasma membrane protein. Its potential function in addition to involvement in Ca2+ entry is being investigated. New reagents to investigate the properties of Orai1 are also being generated.
A number of monoclonal antibodies to platelet membrane proteins are being investigated to further elucidate the functions of platelet plasma membrane receptors. In particular a monoclonal antibody to Glycoprotein 1B (GP1B) is being evaluated. This antibody has been found to inhibit thrombus formation on collagen coated capillaries using whole human blood flowing at intermediate shear rates and slows thrombin stimulated platelet activation at low shear rates. The potential of GP1B as a target of anti-thrombotic therapy will be further investigated.
Protocols in the laboratory use standard techniques of Ca2+ measurement using fluorescent indicators, platelet function tests of aggregation, secretion and surface expression of signalling proteins. Additionally transient and stable transfection of proteins and the use of siRNA technology to silence endogenous channels is present. Dr Authi’s laboratory has a highly specialized technique to prepare plasma and intracellular membranes from human platelets using high voltage free flow electrophoresis. All of the projects noted above have involved national and international collaborations.