Scientific Highlights

Professor Stone is a pharmacologist and neuroscientist with a history of working on adenosine and related purines, glutamate and NMDA receptors, the kynurenine pathway and the biology of serine proteases.

1. TOPIC – demonstration of the reciprocal, opposing actions of cyclic AMP and cyclic GMP on neuronal excitability

Stone TW, Taylor DA & Bloom FE. (1975)  Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex. Science 187, 845-847.

2. TOPIC – pharmacological evidence, in vivo, for glutamate as an excitatory neurotransmitter in the brain

Stone TW. (1976) Blockade by amino acid antagonists of neuronal excitation mediated by the pyramidal tract. J. Physiol.(Lond.) 257, 187-198.

3. TOPIC – discovery of the role of adenosine in mediating effects of morphine in the brain

Stone TW &. Perkins MN. (1979) Is adenosine the mediator of opiate actions on neuronal firing rate? Nature 281, 227-228.

4. TOPIC – modulation of glutamate receptor function by the kynurenine pathway. Quinolinic acid was found to be an agonist at NMDA receptors while kynurenic acid was later shown to be an antagonist

Stone, T.W. & Perkins, M N. (1981) Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS.  Europ. J.Pharmacol. 72, 411-412


Perkins MN & Stone TW. (1982) An iontophoretic investigation of the action of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Research 247, 184-187.

5. TOPIC – the first evidence for biological activity of adenine dinucleotides

Stone TW (1981) – Actions of adenine dinucleotides on the vas deferens, guinea-pig taenia caeci and bladder. Europ. J. Pharmacol.  75, 93-102.

6. TOPIC – functional demonstration of the neural control of brown adipose tissue from the hypothalamus

Perkins MN, Rothwell N, Stock MJ & Stone TW. (1981)  Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 289, 401-402.

7. TOPIC – discovery of the biological activity of amine conjugates with bicarbonate, a finding with major implications for the physiological activity of amines under conditions of varying acidity and carbon dioxide tension.

Lloyd HGE, Perkins MN & Stone TW  (1982) Ethylenediamine as a specific releasing agent of GABA in rat striatal slices.  Neurochem. 38, 1168-1169].


Stone TW & Perkins MN. (1984) Ethylenediamine as a GABA-mimetic. Trends Pharmacol. Sci. 5, 241-243

8. TOPIC – the major importance of the kynurenine pathway in cerebral malaria, with survival increased by kynurenine pathway inhibition, and in trypanosomiasis in which brain damage is reduced.

Clark CJ, Mackay GM., Smythe GA, Bustamante S, Stone TW, Phillips RS (2005) Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. Infection and Immunity, 73, 5249-51.


Rodgers J, Stone T W, Barratt MP, Bradley B, Kennedy, P. G. (2009) Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain 132, 1259-1267.

9. TOPIC – clinical evidence for a potential role of kynurenines in conditions such as Huntington’s disease

Forrest CM, Mackay GM, Stoy N, Spiden SL, Taylor R, Stone TW, Darlington LG (2010) Blood levels of kynurenines, interleukin IL-23 and sHLA-G at different stages of Huntington’s disease. J. Neurochem. 112, 112-122.

10. TOPIC – discovery of the selective depletion of cellular tumour suppressors (DCC, Deleted in Colorectal Cancer, neogenin, unc5) by endogenous and bacterial serine proteases, with implications for understanding the initiation and progression of cancer and their potential prevention.

Forrest CM, McNair K, Vincenten MC, Darlington LG, Stone TW. (2016) Selective depletion of tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin by environmental and endogenous serine proteases: linking diet and cancer. BMC Cancer  16:772. DOI: 10.1186/s12885-016-2795-y.

11. TOPIC – report that inhibition of DNA methylation produces lasting remission in a model of arthritis.

Huang Y-S. et al. (2021) Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis. Proc. Nat. Acad. Sci. USA  118: e2100939118   doi: 10.1073/pnas.2100939118

12. TOPIC – demonstration that certain cancer-related serine proteases induce IDO1, potentially enhancing tumour development

Clanchy FIL, Huang I-S, Ogbechi J, Darlington, LG., Willams, RO, Stone TW (2022) Induction of IDO1 and kynurenine by serine proteases subtilisin, Prostate Specific Antigen, CD26/DPP4 and HtrA: a new mode of immunosuppression. Front. Immunol. 13, art. 832989. doi: 10.3389/fimmu.2022.832989.

13. TOPIC – development of integrated concepts of the neuroimmune interface, including the kynurenine pathway as a focus of ‘reflex’ adaptations to stress

Stone TW, Clanchy FIL, Huang Y-S, Chiang NY, Darlington LG, Williams RO. (2022) An integrated cytokine and kynurenine network as the basis of neuroimmune communication. Front. Neurosci. 16:1002004. doi: 10.3389/fnins.2022.1002004.

Stone, TW, Williams RO (2024) Tryptophan metabolism as a ‘reflex’ feature of neuroimmune communication: Sensor and effector functions for the indoleamine‐2, 3‐dioxygenase kynurenine pathway. J. Neurochem. in press early view: doi: 10.1111/jnc.16015.