Aymen I. Idris MSc. Ph.D.

Senior Lecturer, University of Sheffield.

E Mail - aymen.idris@sheffield.ac.uk

 

Previous Positions:

Lecturer in cancer associated bone disease, University of Edinburgh.

Postdoctoral Fellow, Universities of Edinburgh and Aberdeen.

PhD student, University of Aberdeen.

 

 

 

   

 

 
     

 

 

 

     
     

 

 

   

 

 
     

 

Research Projects


The specific aims of my group’s research at the University of Sheffield are to (a) uncover novel druggable pro-inflammatory signal transduction pathways essential for the regulation of malignant - bone - immune cell interactions, and (b) develop and test new anti-inflammatory agents for the prevention and treatment of skeletal and non-skeletal complications associated with cancer in patients with advanced disease

 

 

Role of Cannabinoids in Metastasis

Dr Silvia Marino MSc. Ph.D.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. The endocannabinoid system is involved in the regulation of a variety of physiological processes including inflammation, bone metabolism and cancer. Dr Marino's work will build on our group previous work on the role of the endocannabinoid system in bone, and attempt to establish whether small molecule inhibitors that selectively target and inhibit the endocannabinoid system might be of value in the treatment of advanced cancer. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in cancer patients with bone metastasis.
 

Previous Publications

Marino S, et al. J. Bio Chem. 2015; 4:290(36): 22049-60. [PubMed]

  

 

Role of Semaphorins in Metastasis and Pain

Miss Danielle De Ridder MSc.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. Semaphorins and their receptors are involved in the regulation of a variety of physiological processes including cell movement and bone metabolism. Miss De Ridder's work will build on our group previous work on the role of Sema-3A in breast cancer-induced osteolysis (De Ridder etal. 2015), and attempt to establish whether administration of Semaphorins and similar peptides might be of value in the reduction of metastasis, inhibition of bone loss and attenuation of pain. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in cancer patients with bone metastasis.
 

Previous Publications

De Ridder D, et al. Bone. 2015; P105. [PubMed]

    

 

Role of TRAF in Cancer Associated Bone Disease

Dr Silvia Marino MSc. Ph.D. and Mr Ryan Bishop MSc.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. Tumour necrosis factor receptor associated factors (TRAFs) play a key role in signal transduction in mammalian cells. Several members of the TRAF family have been identified but only TRAF2 and TRAF6 are implicated in the regulation of osteoclastogenesis.  Dr Marino's and Mrs Bishop's work will attempt to establish whether small molecule inhibitors that selectively target and inhibit TRAF6 might be of value in the treatment of advanced cancer. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in cancer patients with bone metastasis.
 

Previous Publications

Peramuhendige P, Marino, S, et al. Bone. 2014; 3(S1):97. [PubMed]

Peramuhendige P, Marino, S, et al. Bone. 2012; 50(S1): 61 - 62. [PubMed]
  

 

Role of the IKK Epsilon Subunit in Breast Cancer Metastasis

Mr Ryan Bishop MSc.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. The IKK subunit Epsilon is a key protein in NFkB signalling pathway and it has been found to play a key role in signal transduction in mammalian cells. Several members of the IKK family have been discovered but IKK-Epsilon has been identified as a breast cancer oncogene. Mr Bishop's work will attempt to establish whether small molecule inhibitors that selectively target and inhibit IKK- Epsilon might be of value in the treatment of advanced breast cancer. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in breast cancer patients with bone metastasis.
 

  

 

Role of the IKK Alpha Subunit in Prostate Cancer Metastasis

Mr Abdullah Al Jeffery MSc.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. The IKK subunit Alpha is a key protein in NFkB signalling pathway and it has been found to play a key role in signal transduction in mammalian cells. Several members of the IKK family have been identified but IKK-Alpha is implicated in the regulation of both prostate cancer and osteoclastogenesis. Mr Al Jeffery's work will attempt to establish whether small molecule inhibitors that selectively target and inhibit IKK-Alpha might be of value in the treatment of advanced prostate cancer. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in prostate cancer patients with bone metastasis.

  

 

Role of the IKK Beta Subunit in Breast Cancer Metastasis

Dr Silvia Marino MSc. Ph.D.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. The IKK subunit Beta is a key protein in NFkB signalling pathway and it has been found to play a key role in signal transduction in mammalian cells. Several members of the IKK family have been discovered but IKK-Beta is implicated in the regulation of both cancer and bone disease. Dr Marino’s work will attempt to establish whether small molecule inhibitors that selectively target and inhibit IKK-Beta might be of value in the treatment of advanced breast cancer. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in breast cancer patients with bone metastasis.
 

Previous Publications

Marino, S, et al. Bone. 2012; 3(S1): OC5.2. [PubMed]

   

 

Role of RANK in Breast Cancer Metastasis

DR Asim Khogeer MSc.

 

 

 

The majority of deaths from cancer following conventional therapies are a result of metastases. The RANK/RANKL/OPG signalling pathway is known to activate NFkB in mammalian cells. RANK is implicated in inflammation, bone metabolism and cancer. Recently, it became clear that RANK plays a key role in breast cancer tumour growth and bone loss, but the cancer-specific contribution of RANK in the regulation of breast cancer induced osteolysis remains unknown.
Mr Khogeer's work will attempt to establish whether small molecule inhibitors that selectively target and inhibit RANK-mediated signalling might be of value in the treatment of advanced breast cancer. This addresses a huge unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are major clinical problems in breast cancer patients with bone metastasis.

  

 

Cannabinoid Receptors and Osteoclastic Bone Loss

Dr Aymen I. Idris MSc. Ph.D.

 

 

 

The cannabinoid system is involved in the regulation of a variety of physiological processes. In 2005, we identified the link between cannabinoid receptors and the skeleton. In our paper in the Journal Nature Medicine (Idris et al, 2005), we showed that cannabinoid receptors play an important role in regulating bone mass and selective type 1 cannabinoid receptor blockers are potent inhibitors of osteoclast formation and bone resorption in vitro and in vivo. We have recently showed that type 2 cannabinoid receptors are also involved in osteoclastic bone resorption and selective blockers of type 2 cannabinoid receptors inhibited osteoclast formation, fusion, polarisation and bone resorption, with similar potency to type 1 cannabinoid receptor blockers (Idris et al, 2008). These results together identified for the first time both cannabinoid receptors as a novel molecular target for the treatment of osteoporosis and other bone diseases associated with increased osteoclast activity. For an extensive review on the therapeutic use of cannabinoid ligands for the treatment of bone disorders see Idris, 2008.

 

 

Previous Publications and Patents

Aymen I. Idris, Drug News Perspect. 2008; 21(10):533-40. [PubMed]

Idris et al, Cell Metabolism. 2009; 10(2): 139 - 147. [PubMed]

Idris et al, Endocrinology. 2008; 149(11):5619–5626. [PubMed]

Idris et al, Nat Med. 2005; 11(6):1651-1660. [PubMed]

Patent - PCT/GB2004/000858

 

 

 

Cannabinoid receptor blockers induce apoptosis and prevent osteoclast polarisation and formation

 

Control

 

Cannabinoid

blocker

 

 

 

Biphenyl Carboxylic Acid Derivatives (ABD56) for Treatment of Osteoporosis

Dr Aymen I. Idris MSc. Ph.D.

 

 

 

Osteoporosis is a common human metabolic disorder that is characterised by the gradual deterioration of bone mass and architecture, leading to enhance bone fragility and fracture risk. We have developed a series of novel biphenyl carboxylic acid derivatives (e.g. ABD56) that strongly inhibit osteoclast formation and activity in vitro and prevent bone loss due to oestrogen deficiency (Patent 1; Patent 2). Further research in our laboratories has demonstrated that these compounds exert their anti-resorptive effects without affecting osteoblast activity in vitro or blunting the anabolic effects of the parathyroid stimulating hormone (PTH) on bone formation in vivo (Idris et al, 2009). I have recently identified the mechanism of action of these compounds to be based on the inhibition of RANKL-stimulated NF kB activation, a signal transduction pathway that is crucial for osteoclast development and activity (Idris et al, 2008). Because of their selectivity for osteoclast and their lack of effect on the anabolic properties of PTH, these novel agents may be of therapeutic value in combination treatment with PTH for osteoporosis.

 

 

Previous Publications and Patents

Idris et al, Endocrinology. 2009; 150:5-13. [PubMed]

Idris et al, BBRC. 2008; 371 (1): 94-98. [PubMed]

Greig and Idris et al, J Med Chem. 2006; 49 (25):7487-7492. [PubMed]

Patent - PCT/GB2005/002043

Patent - PCT/GB2004/001958

 

 

 

 

ABD56 inhibits RANKL signalling and prevents bone resorption without affecting osteoblasts

 

Control

ABD56

 

 

 

Selective IKK Inhibitors for Treatment of Cancer Associated Bone Loss

Dr Aymen I. Idris MSc. Ph.D.

 

 

 

NFkB activation is vital for osteoclast formation and bone resorption and known to promote the proliferation of cancer cells and the development of metastases. Our extensive pharmacological studies have shown that inhibition of NFkB at the level of either of intracellular proteins such as IKKb or receptor recruitment factor including TAK1 and TRAF6 is equally effective at reducing osteoclast number and preventing osteolytic bone loss. These results indicate that small molecule inhibitors that selectively targets individual components of NFkB signalling may represent promising therapeutic agents for treating both inflammatory and cancer associated bone diseases.

 

Previous Publications

Idris et al, Molecular Cancer Therapeutics. 2009 8:2339-2347. [PubMed]

Idris et al, Eur J Pharmacol. 2009 602 (2-3): 215-222. [PubMed]

Idris et al, Bone. 2004; 35:636-643. [PubMed]

 

 

 

 

IKK inhibitors abolish RANKL induced NFkB activation and prevent osteoclast formation

 

Control

IKK inhibitor

 

 

 

 

C