Dr Jazz Sethi

Group Leader

Senior Research Associate

Senior Scholar in Medicine

Contact Information                

Office Tel : +44 (0)1223 762633

LabTel:      +44 (0)1223 762635

Email:        jks30@cam.ac.uk

PI Profile

Jazz Sethi was educated at Birkbeck College, University of London and received her Bachelors degree (First-Class Honours) in Biological Sciences in 1993. During this time she also held a technical research post in the Department of Clinical Pharmacology and Toxicology, investigating mechanisms of hepatotoxicity with Andre McLean at University College London. In 1997, she obtained a DPhil from Oxford University, based on studies of the regulation of cADP Ribose-mediated calcium signalling in the Department of Pharmacology with Antony Galione. She then moved to Harvard University to investigate the mechanisms of obesity-related insulin resistance alongside Gokhan Hotamisligil. Returning to the UK in 2000, she joined the Department of Clinical Biochemistry at Cambridge University. She has been successively a Fulbright Scholar, Wellcome Trust Prize Travelling Fellow, a RD Lawrence Fellow and a David Phillips Research Fellow. She was elected to a Senior Scholarship in Medicine at Trinity Hall, Cambridge in 2004.

Research Interests

Cytokine Signalling and Energy Homeostasis

Historically, cytokines have attracted much interest due to their ability to cause cellular demise. This toxicity often requires high circulating levels, as is observed during sepsis, cachexia and cancer. However, chronic exposure to low levels of cytokines can also exert profound effects. These actions alter multiple cellular functions and may play a physiological role in regulating cellular metabolism, tissue development, thermogenesis and appetite. Hence, our research interests focus on the actions of the prototypical cytokine, TNF alpha and elucidating the signalling mechanisms by which its actions are manifested in metabolically relevant tissues.

TNF alpha (or Tumor Necrosis Factor alpha) is a multifunctional cytokine that mediates its effects via two cell surface receptors (see figure). These are ubiquitously expressed and differ primarily in their intracellular signalling domains. Both TNF and its receptors are produced by adipose tissue where it can affect normal adipocyte development as well as key functions such as insulin sensitivity, lipid metabolism and adipokine production. These actions can themselves go on to impact on systemic sites to alter whole body energy homeostasis. Understanding how TNF signals in adipocytes is important if we wish to identify novel targets for therapeutic intervention in obesity-related metabolic disorders. To this end, we are currently investigating the mechanisms of TNF signalling in insulin resistance, adipocyte development and cross-talk with growth factor signalling.

Our research utilises a multidisciplinary approaches including basic protein biochemistry, pharmacology, cellular molecular biology, as well as modern systems biology and bioinformatics. These are all used in conjunction with numerous of our own genetically modified cellular models and are further complimented by numerous local, national and international collaborations.

Key Research Areas

•  Molecular mechanisms of insulin resistance

 

•  Molecular mechanisms of anti-adipogenesis

•  Signal transduction networks in cytokine and growth factor signalling

<< Ribbon diagram of insulin receptor substrate pleckstrin homology domain showing that serine 24 (spheres) lies in close proximity to the basic residues (red sticks) implicated in lipid binding. We have shown that Serine 24 is phosphorylated by protein kinase Cs and that this modification is sufficient to inhibit protein-lipid interactions of IRS-1. (Nawaratne etal., Mol. Endocrinol. 20(8):1838-1852, 2006)

 

 

 

Funding

Current Group Members

* Joint with A Vidal-Puig    ^ Joint with S O'Rahilly

Past Group Members

Publications & Other Links

• Publications in PubMed

• Full Publications List

• PhD Studentship Vacancies

• Other Vacancies