Personal profile

Overview

The human body responds to stress by producing a set of stress hormones (POMC, ACTH and glucocorticoids) which have multiple actions, but primarily increase factors which fuel our body to help it respond to stress. However, long term (chronic) stress is bad for us, and we believe this is because there are subtle changes in stress hormones, which increase the risk of diabetes and heart disease. We are working on ways to measure these subtle changes in stress hormones in models of obesity and diabetes and in different groups of patients. Stress hormones can also affect the networks in the brain that regulate food intake and energy balance. We are studying how this goes wrong in obesity and diabetes. We are also investigating how undernourishment in pregnancy affects these networks in the baby’s brain so that they are more likely to become obese as adults. Some cancers can also secrete hormones. In small cell lung cancer, the precursor protein from which ACTH is produced, proopiomelanocortin (POMC), is expressed and released into the blood. We are developing techniques that utilise this secreted POMC in the monitoring of tumour progression and response to treatment.

Biography

Anne White is Professor of Endocrine Sciences within the School of Medical Sciences in the Faculty of Biology, Medicine and Health where she was Associate Dean for Business Development and on the Faculty Management Team.  Anne became a Fellow of the Society of Biology in 2010.

Anne gained her PhD in Cell Biology at the University of Manchester in 1978 and has pursued a translational research career initially as a Lecturer in Clinical Biochemistry in 1989 and then as Senior Lecturer in 1991, Reader in 1995 and was appointed to a personal Chair in 1999. From 1994 to 1998, Anne was Head of the Division of Cells, Immunology and Development in the School of Biological Sciences.

In 2002, Anne became Head of Graduate Education, and subsequently Associate Dean for Graduate Education, in the Faculty of Medical and Human Sciences, with overall responsibility for more than 1000 graduate students. She was a member of the MRC Training and Career Development Board from 2002-2011 and has since Chaired several of the MRC panels for studentships.

Anne has pursued interests at the interface with cellular/molecular endocrinology and its direct translation to endocrine disorders. This has led to over 130 full publications, chapters and reviews. She has been invited to speak not only at international conferences, but also to clinical groups, and researchers in pharmaceutical and diagnostic companies. The majority of her published work has derived from Wellcome Trust, Research Council and NHS funding. In addition, she has research funding from collaboration with industrial partners to underpin programmes on therapeutic targets and develop diagnostic assays.

As part of a Royal Society Industry Fellowship, Anne worked with AstraZeneca from 1999-2002, extending her interests in prohormone processing to neuropeptides in food intake and obesity. Anne has had a number of roles in the Society for Endocrinology. In 2000 she was elected to a five year appointment on the Executive Board of the Council of the Society and became a Director of BioScientifica.  In 2010 Anne was appointed to the Council of the Society for Endocrinology.

Research interests

Role of glucocorticoids in diabetes and obesity

Many people take steroids (glucocorticoids) for a range of inflammatory conditions and autoimmune disorders. However although they are extremely beneficial they do have a number of side-effects and chronic treatment with glucocorticoids can lead to type 2 diabetes.

This is not surprising as endogenously produced glucocorticoids such as cortisol have a range of metabolic effects. While quite a lot is known about their actions on peripheral organs such as the liver relatively little is known about their actions in the hypothalamus. This is surprising as they are known to regulate both POMC gene expression and therefore αMSH production and AgRP synthesis.

As a group we are interested in examining how chronic glucocorticoid treatment acts on the neuropeptide networks in the hypothalamus to cause metabolic abnormalities. We use a mouse model where we treat with corticosterone in the drinking water and after 24 hours the mice increase their food intake and by three weeks they have an increased body weight and insulin resistance with some tendency to hyperglycaemia.

 

Programming of energy balance: role of maternal diet and stress hormones

We are interested in understanding how undernutrition and overnutrition during pregnancy affects the baby leading to an increased chance of developing obesity and diabetes. We have shown that this alters the epigenetic status of genes involved in the regulation of appetite and HPA axis function. Our work was aimed at determining how these programmed changes occur ( former collaboration with Prof. Frank Bloomfield in New Zealand and Prof. John Challis in Canada).

 

 

Assessment of Stress Hormones

POMC processing

Pro-opiomelanocortin (POMC) is the precursor of the hormone adrenocorticotrophin (ACTH), and processing varies in different tissues. We study mechanisms regulating production of active hormones and utilise a panel of highly sensitive antibodies, generated by the group, to detect the different products of POMC. This allows us to determine which peptides are being produced by different cell types and in different disease states. 

 

POMC secretion by tumours

We have previously shown that many tumours, but particularly small cell lung cancer (SCLC), express POMC and release it into the blood. SCLC is an aggressive neuroendocrine tumour that has a poor prognosis. Our group is interested in investigating POMC as a novel biomarker for SCLC using xenograft models (A and B below). There is evidence to show that SCLC has a dual phenotype exhibiting both neuroendocrine and epithelial markers (C). We are interested in the importance of this dual phenotype during metastasis and whether SCLC cell lines and xenografts show heterogeneity of these markers. More recently we have started investigating the significance of the heterogeneity in resistance to chemotherapy and radiotherapy.

A. SCLC xenograft tumour stained for POMC (brown). Nuclei are stained with blue. B. Circulating POMC levels mirrors tumour growth in mice with xenografts.

 

Methodological knowledge

  • Molecular Endocrinology techniques including transfection analysis, reporter gene assays
  • Mouse models of chronic glucocorticoid treatment
  • Immunoassay development and immunocytochemistry
  • Monoclonal antibody production
  • Purification and characterisation of peptides by immunoaffinity analysis, HPLC and western blotting
  • Characterisation of human small cell lung cancer cell lines, cloning and stable transfection analysis

Memberships of committees and professional bodies

  • Chair MRC Doctoral Training Grants Panel 2009-2011
  • Chair MRC Capacity Building Studentships Panel 2008-2011
  • Panel member MRC Training & Careers Group 2010-2011
  • Society for Endocrinology
  • The Endocrine Society (USA)
  • British Society for Neuroendocrinology

My collaborations

Dr Tony Coll
Institute of Metabolic Science
Cambridge
 
Dr Iris Lindberg
University of Maryland,
Baltimore
 
Professor Malcolm Low
University of Michigen
Ann Arbor
 
Dr Florian Merkle
Institute of Metabolic Science
Cambridge
 
Professor Sharon Wardlaw
Columbia University College of Physicians and Surgeons,
New York
 
Professor Kaye Williams
University of Manchester
 
Dr Giles Yeo
Institute of Metabolic Science
Cambridge
 

 

 

My group

  • Dr Erika Harno
  • Dr Charlotte Sefton
  • Tiffany-Jayne Allen
  • Leanne Walker

Social responsibility

We participate in events with high school children where they come from all over the North West of England  to the University to learn more about science. This is a highly interactive format during which our group runs a “Diagnosing diabetes” workshop.

During the workshop the activities for the students include:

  • Measuring the levels of glucose and diagnosing subjects as to whether they may or may not have diabetes.
  • Chromatography to investigate glucose, insulin and free fatty acids
  • Food evaluation for calorie content
  • Quiz on diabetic complications

We also take part in the National Science and Engineering Week. Previously, we have created a stand to help teenagers demonstrate their understanding of what a balanced meal would be and we have tackled issues such as obesity and anorexia.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 2 - Zero Hunger
  • SDG 3 - Good Health and Well-being

Areas of expertise

  • RZ Other systems of medicine
  • Endocrinology
  • Stress hormones
  • neuropeptide regulation and obesity
  • diabetes

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