Dr Timothy Smith

Dr Timothy Smith
PhD (Manchester) BSc (London) MRSB, FIBMS

Senior Research Fellow

Overview

Contact Details

Telephone
work +44 (0)1224 553208
Fax
fax 552514
Email
Address
The University of Aberdeen School of Medicine, Medical Sciences and Nutrition, Biomedical Physics Building (B3) University of Aberdeen Foresterhill Aberdeen AB25 2TN
Research

Research Interests

Development of novel tracers for medical imaging

Nanoparticles for cancer imaging and therapy

Targeted Radiotherapy

Using 31P-NMR spectroscopy to probe intracellular pathways

Molecular imaging to detect beneficial drug combinations

Anticancer drugs and phospholpid metabolism

PhD opportunities:  I welcome applications from self-funded students who are interested in these areas. 

Current Research

Nanoparticles for cancer imaging and therapy

Nanoparticles are particles of the order of 10-6 mm in size. They can be used as platforms on which to anchor targeting molecules including antibodies and beacons such as imaging radioactive atoms or cytotoxic radioactive atoms. Targeting molecules facilitate the binding of the nanoparticle to molecules such as receptors that are abnormally expressed on the surface of cancer cells. The beacons can include radioactive metals including 111In which can be detected using a medical imaging technique called SPECT (single proton emission tomography) or with positron emitting metals such as 64Cu which can be detected using positron emission tomography (PET).  Cytotoxic radioactive atoms include β-emitters including 90Y and 177Lu and are used for targeted radiotherapy (see below).

Targeted Radiotherapy

Cancer patients often present with metastatic disease where the primary cancer has spread to other parts of the body. Radiotherapy is very effective anticancer treatment for cancers that cannot be surgically removed it cannot be used to control metastatic spread. Currently chemotherapy is the mainstay for metastasis treatment but cancer cells almost always develop resistance to chemotherapy. Molecular radiotherapy involves administering, intravenously, radioactive targeted drugs which seek out primary tumours and metastasis and use their radioactive payload to locally irradiate cancer tissue. However the distribution of sufficient cancer cell killing activity throughout a cancer to enable complete destruction of the cancer is problematic. We are optimising this technique to deliver the necessary high radiation dose to primary tumours and their metastasis.

Using 31P-NMR spectroscopy to probe intracellular pathways

Intracellular signalling pathways such as the Akt pathway serve as essential links between cell surface receptors and cellular processes including proliferation, development and survival. The Akt pathway has many downstream targets including glycogen synthase kinase 3 (GSK3) which is a major regulatory kinase for cell cycle transit as well as controlling glycogen synthase activity.  However links between different components of the Akt pathways are not fully characterised.

31P-NMR (nuclear magnetic resonance) spectroscopy is a non-invasive technique that detects phosphorous-containing metabolites in cells, tissues and chemical extracts. It is also used clinically to monitor response to anticancer drugs which induce changes in the concentration of 31P-NMR –detectable molecules including phospholipid metabolites such as PCho.  We are interested in the application of 31P-NMR spectroscopy to understanding interconnections between different components of the pathway including phosphoinositide-3-kinase (PI3K) and GSK3. These studies also inform on the effectiveness of clinical 31P-NMR spectroscopy to detect response to anticancer drugs that target intracellular signalling pathways.  

 Molecular imaging to detect beneficial drug combinations

Cancer drugs are frequently administered in combinations of 2 or more drugs to enhance their anticancer effectiveness and to overcome cancer resistance to individual drugs. Some drugs enhance the effect of each other resulting in increased cancer control but other combinations can interfere with each other decreasing the overall anticancer effect compared with each drug given singly.  We are exploring whether or not molecular imaging techniques could be used to detect the anticancer effectiveness of drug combinations.

 

Research Grants

Current Funding

Smith TAD, McLaughlin AC, Trembleau L. Development of targeted nanoparticles loaded with beta-emitting nuclides for molecular radiotherapy. TENOVUS Scotland £11.3K 1/7/16 to 31/12/2017

Smith TAD, McLaughlin AC, Trembleau L, Flux G. Preclinical optimisation of targeted nanoparticles loaded with beta-emitting radionuclides for molecular radiotherapy. Chief Scintists Office (Scottish Government). £265K 1/1/2017-31/12/2018



 

Teaching

Teaching Responsibilities

I am responsible for delivering the biochemical and most of the physiology elements of the Biomedical Physics MSc courses.

Publications

Publications 

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