Dr Nimesh Mody

Dr Nimesh Mody
Ph.D. Biochemistry, B.Sc. Biochemistry,

Senior Lecturer

Overview
Dr Nimesh Mody
Dr Nimesh Mody

Contact Details

Telephone
work +44 (0)1224 437102
work +44 (0)1224 437411
Email
Address
The University of Aberdeen Institute of Medical Sciences (room 5.27)
School of Medicine, Medical Sciences & Nutrition
Foresterhill Health Campus
Aberdeen AB25 2ZD
Scotland, UK

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Biography

Current position: Senior Lecturer - since Aug 2017. Aberdeen Cardiovasular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition and Institute of Medical Sciences. (tenured Lecturer since Sept 2014).

Research Fellow, Aug 2011 - Aug 2014. Cardiovascular research programme (Institute of Medical Sciences, since Aug 2012).

(Intermediate) Basic-Research Fellow
- University of Aberdeen, Sep 2009 - 2013

Postdoctoral Research Fellow - University of Aberdeen, Sept 2007-Aug 2011
Working closely with Prof. John Speakman, Integrative Physiology, Institute of Biological & Environmental Sciences.

Postdoctoral Research Fellow - Harvard Medical School, Nov 2003 - Jul 2007
Prof. Barbara Kahn's laboratory, Division of Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA.

PhD (Biochemistry) - University of Dundee, Oct 1999 - Jul 2003
Supervisor : Prof. Sir Philip Cohen, MRC Protein Phosphorylation Unit.

BSc (Biochemistry) - University College London, Oct 1995 - Jun 1998
First Class with Honours.

Research

Research Interests

Highlights:

  • Investigating how our bodies adapt to changing food intake in terms of accumulating fat and controlling blood glucose levels.
  • Understanding how increasing amounts of fat and high blood glucose levels leads to changes in protein levels and has effects on the DNA in cells that make up fat, liver and muscle.
  • Increasing our knowledge of how these integrated pathways (from DNA to the whole body) that are no longer controlled well in disease, can help us to identify new drug targets to combat obesity and type-2 diabetes.

Obesity levels are rising worldwide to epidemic levels and this is of major concern to governments and health services, because obesity is often accompanied by serious co-morbidities such as type 2 diabetes and cardiovascular disease. With a concurrent rise in the incidence of type 2 diabetes and with around 80% of people being overweight at the time of diagnosis, obesity has been identified as the number one risk factor for the development of type 2 diabetes.  Type 2 diabetes develops from insulin resistance, which is characterised by impaired insulin action in skeletal muscle, adipose tissue and liver. Over the past 15 years it has become apparent that adipose tissue acts as an endocrine organ secreting many factors (adipokines), some of which have been directly implicated in the development of insulin resistance and diabetes. One such factor recently identified is the serum retinol-binding protein (Yang Q, Graham TE, Mody N, others and Kahn BB. Nature 2005, now cited over 1000 times).

Another key defect in obesity is the downregulation of the transcription factor PPAR-gamma. Anti-diabetic drugs such as TZDs eg. rosiglitazone (brand name Avandia) act via PPAR-gamma have been widely studied in mouse models of obesity and insulin resistance. They were also widely used  in humans but problems such as weight gain and increased risk of cardiovascular problems has meant these drugs are no longer available to patients and alternative therapies are needed. Thus understanding the signalling pathways that are impaired in disease can help us to identify new drug targets to combat obesity and type-2 diabetes.

What is diabetes? - Great animation @ Diabetes UK.

Diabetes and the heart - information and video at British Heart Foundation.

Metabolic Syndrome e-poster @ Nature Medicine, from neuronal control of food intake to macrophage infiltration and adipose inflammation.

Understanding animal research - The public debate on animal research sometimes gets so heated that the facts can be overlooked. Learn more at this site.

Current Research

Physiological and molecular link between obesity and insulin resistance in mouse models

We are studying the interplay between genetic background and environmental challenges that lead to the development of obesity and type 2 diabetes. We are currently interested in the way the body uses vitamin A (or retinol).

Our current research was highlighted by the Mail on Sunday (6 Jan 2013, page 13) as the ‘Magic bullet’ hope for battling obesity - Drug could prevent weight gain from junk food. Click here to read more, but scroll down the page to find the article.

Mice fed high-fat diet rapidly undergo many molecular and physiological changes such as gain adipose (fat) mass and become insulin resistant. Prolonged exposure to a high-fat diet leads to full blown obesity, severe insulin resistance, hyperglycemia and diabetes. My research aims to provide further insight into the mechanism of diet-induced obesity and insulin resistance and identify novel molecular target(s) for the development of new, more potent therapies to treat obesity and prevent diabetes.

Retinol homeostasis is tightly regulated by a complex system of enzymes and carriers that can promote the 1) storage of retinol in the form of retinyl-esters (RBP4, cellular RBP1, CRBP1 and lecithin:retinol acyltransferase, LRAT), 2) metabolism to retinoic acid (RA) and signalling through its receptors (retinaldehyde dehydrogenase, RALDH1, cellular retinoic acid-binding protein, CRABP and RA receptors, RAR’s), 3) degradation via cytochrome P450 type enzymes, CYP26A1.  It has long been known that RA potently blocks adipogenesis when introduced at early stages of differentiation. More recently, the importance of retinoid homeostasis in whole body energy balance and glucose homeostasis has been highlighted in genetic knockout studies of RALDH1 (lean phenotype), CRBP1 and CRABP1 (obese phenotype). We are investigating roles of these proteins in different tissues and using retinoids to investigate signalling pathways altered in obesity and insulin resistance.

Key reference: McIlroy, GD., Delibegovic, M., Owen, C., Stoney, PN., Shearer, KD., McCaffery, PJA. & Mody, N. . 'Fenretinide Treatment Prevents Diet-Induced Obesity in Association With Major Alterations in Retinoid Homeostatic Gene Expression in Adipose, Liver and Hypothalamus'. Diabetes, 2013 Mar, vol 62, no. 3, pp. 825-836.  [Online, 27 Nov 2012] DOI: 10.2337/db12-0458

 Fenretinide on 3T3L1 adipocyte differentiation

Molecular approaches: we are using the latest and best high-resolution chemiluminescence digital imaging for western blotting to measure protein expression and insulin signalling changes. We also use real-time PCR to monitor gene expression changes.

Collaborations

Lab members with visiting summer students this, July 2013
We have a joint-lab structure with Prof. Mirela Delibegovic (IMS) - her main interest is the role of protein tyrosine phosphatase 1B (PTP1B) in cell signalling, obesity and diabetes.  Juliana Luchin (2nd from left) was a visiting medical student from Brazil (July 2013). She performed western blotting on mouse tissue lysates from our high-fat diet studies during her 4 week stay in our lab.

Cross-college interactions with researchers at the Institute of Biological & Environmental Sciences eg. Energetics research (Prof. John Speakman) and the Rowett Institute of Nutrition & Health eg. Obesity and Metabolic Health Theme (Prof. Julian Mercer, Prof. Peter Morgan and Dr. Perry Barrett).

See the College of Life Sciences and Medicine website.

Invited speakers for recent obesity and diabetes seminars

2015

  • Prof. Susanne Mandrup, University of Southern Denmark.
  • Dr. Rob Semple, University of Cambridge.
  • Prof. Nik Morton, University of Edinburgh, Centre for Cardiovascular Science
  • Dr Zoi Michailidou, University of Edinburgh, Centre for Cardiovascular Science

Research Grants

British Heart Foundation - project grant (2017-2020), principle investigator leading a Scotland-wide collaborative grant with chemist Matteo Zanda (Aberdeen), vascular biology expert Patrick Hadoke (Edinburgh), lipid analysis specialists (Phil Whitfield and Mary Docherty in Inverness). Investigating new drugs to prevent lipotoxicity, insulin resistance and vascular endothelial dysfunction.

Wellcome Trust - Institutional Strategic Seed Fund, ISSF, (2015-2016)

Tenovus Scotland project grant (2015-2016), principle investigator. Genome-wide binding studies to interrogate retinoic acid receptor signalling in models of obesity and type 2 diabetes.

The Royal Society (of London) research grant 2013-2014, principle investigator.

Tenovus Scotland project grant (2013-2014) co-investigator (with Dr. Mirela Delibegovic)

Kosterlitz Centre for Therepeutics project grant (2013-2014) co-investigator (with Prof. Bettina Platt and Dr. Mirela Delibegovic)

British Heart Foundation Intermediate Basic Science Research Fellowship (2009-2013)

EFSD/Lilly European Diabetes Research Programme Grant (2012 - 2013) Principal Investigator (co-PI with Dr. Mirela Delibegovic)

Tenovus Scotland - small research grant (2011), Mathematical Understanding of Obesity and Type 2 Diabetes in mouse models. In collaboration with Scottish Crucible participant Liangxui Han (now School of Computing, Mathematics and Digital Technology, University of Manchester).

Scottish Crucible Interdisciplinary Group Project Award

2013 Space to Pace: making Scottish green space accessible

2010
1. Using optoelectronic tweezers on cells to measure biomarkers of ageing and obesity;
2. Using a novel method to prepare of food emulsions.

The Biochemical Society Summer Vacation Studentship - awarded to Petros Stathakos (University of Aberdeen undergraduate student).Petros in the lab.

European Association for the Study of Obesity (EASO) Travel Award (2009) to attend the European Congress on Obesity (ECO) 2009, 6th - 9th May, Amsterdam.


Career Development Fellowship (2007-09)
College of Life Sciences & Medicine, University of Aberdeen.

Trans-Atlantic Postdoctoral Fellowship (2006-07)
American Diabetes Association - European Association for Study of Diabetes.

Postdoctoral Fellowship (2004-06)
American Heart Association (Northeast Affiliate).

Teaching

Teaching Responsibilities

Laboratory-based research-led teaching. Final year (Honours) students take projects in our current areas of research. Including 20-week research projects for medical students performing Intercalated BSc in Medical Sciences (for details see tab on "Further Info" and scroll down to "BSc Hons students").

I am a Lecturer on:

  • BC3503 - The Molecular Control of Cell Function. 3rd year course, I cover aspects of metabolic disease, insulin and nutrient signalling.
  • BI25M7 - Energy for Life. 2nd year Biochemistry course, I give tutorials aimed at recapping and discussing taught material about metabolism and enzymes.
  • BI2508 - Principles of Animal Physiology, - 2nd year course for Zoology students.
  • BI1006 - 1st year Biology tutorial course, tutor.
Further Info

External Responsibilities

Peer reviewer for Diabetologia, The Journal of Clinical Endocrinology & Metabolism and Nature Scientific Reports.

Admin Responsibilities

Senate - Responsibility for the governance of the University which rests with the University Court and the Senatus Academicus (Senate). The Senate is responsible for the regulation and superintendence of teaching and for the promotion of research.

Athena SWAN award (for the University of Aberdeen) Self-Assessment Team member. The Athena SWAN Charter recognises and celebrates good employment practice for women working in science, engineering and technology (SET) in higher education and research.

Conference presentations

Diabetes UK Professional Conference (Mar 2015 London; Mar 2013 Manchester, UK), Poster.

Systems Approach to Metabolic Disease (Cell Symposia, Oct 2014, Chicago, IL, USA), Poster.

Nuclear receptors: Linking molecules, genomes & physiology (EMBO Conference, September 2013, Sorrento, Italy). Poster.

participants_EMBO_Sorrento_2013

Close-up

close-up

Programming Obesity: Central and Peripheral Contributors (Abcam sponsored meeting, Apr 2013, Cambridge, UK). Invited speaker.

Diabetes & obesity: getting to the heart of the matter - Joint conference : The Academy of Medical Sciences and The Royal Society of Edinburgh Supported by The Caledonian Research Fund. (The Royal College of Physicians, Edinburgh, May 2010).
- Invited poster presentation

UK Adipose Tissue Group meeting (Astra Zeneca, Alderley Park, Dec 2009).
- Invited poster presentation

7th James Black Conference - Joint Meeting of The Physiological Society & British Pharmacological Society. "Integrative Pharmacology and Physiology: translating "omics" into functional and clinical applications (King's College London, Sep 2009).
- Invited poster presentation

Scottish Society for Experimental Medicine (Aberdeen, May 2009)
- Invited speaker

European Congress on Obesity 2009 (Amsterdam, May 2009)
- Invited speaker - "Fenretinide prevents high fat diet induced obesity and associated hyperleptinemia and insulin resistance".

ACERO Symposium 13 (Aberdeen, May 2008)
- Invited speaker

Memberships & other activities

  • Scottish Crucible 2010 - a professional & personal leadership and development programme developed for early to mid-career researchers in the Scottish research community.
  • The Biochemical Society - Grants are available for stipends of £200 per week for 6 – 8 weeks, and up to £1,600 in total, to support a summer placement in a lab for an undergraduate student (eg. Petros Stathakos, see below). Contact me if you interested in getting valuable lab experience.
  • The Physiological Society - brings together over 3000 scientists from over 60 countries. Since its foundation in 1876, its Members have made significant contributions to our knowledge of biological systems and the treatment of disease.

  • Association for the Study of Obesity (ASO) is the UK’s foremost charitable organisation dedicated to the understanding and treatment of obesity. ASO is affiliated to the European and International Associations for the Study of Obesity.
  • Aberdeen Center for Energy Regulation & Obesity (ACERO)- its principal aim is to promote collaboration between scientists within the Aberdeen area who have interests in the study of energy balance and regulation in the context of the development of obesity.

Staff/students

PhD studentships

George Mcilroy, BBSRC funded Oct 2010 - Oct 2014, to investigate the molecular mechanisms involved in the progression of diet-induced obesity and insulin resistance in mice. Will defend his thesis by the end of 2014 and has started a postdoc with Dr. Justin Rochford here in Aberdeen.

 

Nicola Morrice, 2013-2017 University of Aberdeen, Centre for Genome Enabled Biology & Medicine (CGEBM) Studentship. CGEBM aims to accelerate discovery in genome-enabled research across the University of Aberdeen via provision of various genomic technologies, including next generation DNA sequencing and bioinformatic support.

BSc Hons students

Nimesh Mody and Mirela Delibegovic's lab members in the Zoology Building

   Left to right :Petros Stathakos, Carl Owen (Delibegovic lab), Claire Henderson, George Mcilroy, Nimesh Mody, Mirela Delibegovic in the Zoology Bulilding.

 

  • Olga Kochman (2012-2013) MSci, Biomedical Science (Anatomy) with Industrial Placement at AstraZeneca, acheived 1st Class Honours, and was awarded the Biomedical Science (BMS) Prize for the best student.
  • Stephane Schroder (2011-12), Katie Towle (2010-11) Zoology BSc, 10-week research project
  • Liam Mcallan, 2008-09 Zoology BSc, 10-week research project and followed by further summer work experience, undertook a PhD at Moorepark Food Research Center, Ireland. Liam is now a Postdoctoral Researcher at University of Tennessee Health Science Center. Check out his LinkedIn page
 Intercalated BSc in Medical Sciences, 20-week research project for medical students.
  • Eleanor Moncur (2013-14), project with Mirela Delibegovic investigating dietary interventions such as methionine restriction in improving obesity and type-2 diabetes. Eleanor has published work from her project in Aging Cell.
  • Jenny Reekie (2011-12), presented her work on Fenretinide at Diabetes UK annual conference, Manchester 2013.
  • Claire Henderson, (2010-11), presented her work on Fenretinide at Heart UK annual conference, Newcastle 2012 and manuscript is undergoing peer-review following submission for publication.

Impact of Research

Clinical trials

Effect of Fenretinide and Low-Dose Tamoxifen on Insulin Sensitivity in Premenopausal Women at High Risk for Breast Cancer (Johansson et al 2008......Link)

A Randomized, Double-Blind Study of the Effects of Fenretinide Administered in Subjects With Obesity (Veterans Medical Research Foundation, Oct 2007, Estimated Study Completion Date: April 2015....Link )

International collaboration

Chinese delegation visits University ...news archive

Publications

Publications