Nuclear receptors and human disease. (360G-Wellcome-080237_Z_06_Z)

£955,795

Many drugs are targeted at nuclear receptors and our aim is to investigate their role in human disease. Wellcome Trust support (1990-2006) has enabled us to identify and study the largest worldwide cohort (~200 families) with Resistance to Thyroid Hormone (RTH) and thyroid hormone receptor beta (TRbeta) mutations or insulin resistance with defects in peroxisome proliferator-activated receptor gamma (PPARgamma). Key future research goals are to: identify & functionally characterise novel genetic defects in human TR & PPARgamma signalling; characterise their phenotype to elucidate pathophysiological mechanisms; study defective receptor-containing human cells/tissues ex vivo. As well as TRbeta mutations, we will seek novel genetic defects mediating RTH and a human homologue of murine TRalpha resistance. We will investigate phenotypes of disordered energy expenditure & appetite, lipid and glucose homeostasis in RTH and use gene expression profiling to investigate pathogenic mechanisms and responses to treatment. We will identify novel PPARgamma gene defects in human metabolic phenotypes and elucidate molecular mechanisms by which germline or somatic (Pax8-PPARgamma) dominant negative forms of PPARgamma interfere with receptor function. We will investigate the metabolic phenotype and its treatment in vivo, and consequences of defective PPARgamma signalling in human primary cells ex vivo.

Where is this data from?

This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.

Grant Details

Amount Awarded 955795
Applicant Surname Chatterjee
Approval Committee Physiological Sciences Funding Committee
Award Date 2006-07-11T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Programme Grant
Internal ID 080237/Z/06/Z
Lead Applicant Prof Krishna Chatterjee
Other Applicant(s) Dr M Gurnell
Partnership Value 955795
Planned Dates: End Date 2011-07-31T00:00:00+00:00
Planned Dates: Start Date 2006-08-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England