Dr NIMESH MODY
Independent Research Fellow (in Integrative Physiology)
B.Sc. Biochemistry, Ph.D. Biochemistry
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Personal Details
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Biography
Research Fellow/Lecturer - Aug 2011-present. Cardiovascular research programme at the Institute of Medical Sciences (from Oct 2012).
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(Intermediate) Basic-Research Fellow - University of Aberdeen, Sept 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.
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Research Interests
Signalling pathways in disease, particularly those related to 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 700 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.
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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. 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.
We are currently interested in the way the body uses vitamin A (or retinol). 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 in press)
[Online, 27 Nov 2012] DOI: 10.2337/db12-0458
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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. |
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Collaborations
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Dr Mirela Delibegovic (Senior research fellow within IMS) - the role of protein tyrosine phosphatase 1B (PTP1B) in obesity and diabetes. |
- Caloric restriction to promote healthy ageing - Dr. Colin Selman
- Glucose and lipid homeostasis - Dr Mirela Delibegovic
- Retinoic acid signalling in the CNS - Prof. Peter McCaffery
- Mouse models of Alzheimer's disease - Prof. Bettina Platt
Cross-college interactions with researchers at the Institute of Medical Sciences and the Rowett Institute of Nutrition & Health. The College of Life Sciences and Medicine website.
Invited speakers for recent obesity and diabetes seminars
Dr. Lora Heisler, University of Cambridge, School of Biological Sciences
Dr. Nina Balthasar, University of Bristol, School of Medical Sciences
Dr. Satish Patel, University of Cambridge, Metabolic Research Laboratories, David Savage group.
Dr. Graham Rena, University of Dundee, Ninewells Hospital
Dr. Kerry McInnes, University of Edinburgh, Centre for Cardiovascular Science
Dr. Kei Sakamoto, Nestlé Institute of Health Sciences, Lausanne (previously MRC Protein Phosphorylation Unit, University of Dundee).
Dr. Nik Morton, University of Edinburgh, Centre for Cardiovascular Science
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Research Grants
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 2010 Interdisciplinary Group Project Award - two small grants awarded,
1. A novel method to measure biomarkers of ageing and obesity
2. Novel preparation of food emulsions.
The Biochemical Society Summer Vacation Studentship - awarded to Petros Stathakos (University of Aberdeen undergraduate student).
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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).
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Teaching Responsibilities
Lecturer on Principles of Animal Physiology, BI2508 - 2nd year course for Zoology students.
Tutor on 1st year Biology tutorial course, BI1006.
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External Responsibilities
Peer reviewer for Diabetologia.
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Conference presentations
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
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Memberships & other activities
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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.
- Association for Early-Career Biology Researchers in Old Aberdeen, University of Aberdeen
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Staff/students
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PhD studentship - George Mcilroy, BBSRC funded Oct 2010 - 2013, to investigate the molecular mechanisms involved in the progression of diet-induced obesity and insulin resistance in mice. |
BSc Hons students
- Petros Stathakos (University of Aberdeen undergraduate student) - awarded The Biochemical Society Summer Vacation Studentship, (Summer 2011). See Petros's blog on the Biochemical Soceity website and article in the "The Biochemist" magazine article pdf
- Stephane Schroder (2011-12), Katie Towle (2010-11) Zoology BSc, 10-week research project
- Jenny Reekie (2011-12), Claire Henderson, (2010-11) Intercalated BSc in Medical Sciences, 20-week research project
- Liam Mcallan, 2008-09 Zoology BSc, 10-week research project and followed by further summer work experience, now undertaking postgraduate studies (PhD) at Moorepark Food Research Center, Ireland.
- McAllan L, Cotter PD, Roche HM, Korpela R, Nilaweera KN.
Impact of leucine on energy balance. J Physiol Biochem. 2012 Apr 26. [Epub ahead of print] PubMed PMID: 22535285.
- McAllan L, Cotter PD, Roche HM, Korpela R, Nilaweera KN.
Left to right :Petros Stathakos, Carl Owen (Delibegovic lab), Claire Henderson, George Mcilroy, Nimesh Mody, Mirela Delibegovic in the Zoology Bulilding.
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Impact of Research
Clinical trials
Effect of Fenretinide and Low-Dose Tamoxifen on Insulin Sensitivity in Premenopausal Women at HighRisk 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 ....Link )
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Publications
- McIlroy, GD., Delibegovic, M., Owen, C., Stoney, PN., Shearer, KD., McCaffery, PJ. & Mody, N. Fenretinide Treatment Prevents Diet-Induced Obesity in Association With Major Alterations in Retinoid Homeostatic Gene Expression in Adipose, Liver and Hypothalamus, Article, 2013, Diabetes, 62, 3, pp825 - 836, ISSN/ISBN: 0012-1797
- Owen, C., Czopek, AJ., Agouni, A., Grant, L., Judson, RN., Lees, EK., McIlroy, GD., Göransson, O., Welch, A., Kendra Bence, K., Kahn, B., Neel, BG., Mody, N. & Delibegovic, M. Adipocyte-Specific Protein Tyrosine Phosphatase 1B Deletion Increases Lipogenesis, Adipocyte Cell Size and is a Minor Regulator of Glucose Homeostasis, Article, 2012, PLoS ONE, 7, 2 - e32700, ISSN/ISBN: 1932-6203
- Hoggard, N., Agouni, A., Mody, N. & Delibegovic, M. Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes, Article, 2012, International Journal of General Medicine, 5, pp403 - 411
- Agouni, A., Mody, N., Owen, C., Czopek, A., Zimmer, D., Bentirez-Alj, M., Bence, KK. & Delibegovic, M. Liver-specific deletion of protein tyrosine phosphatase (PTP) 1B improves obesity- and pharmacologically-induced endoplasmic reticulum stress., Article, 2011, Biochemical Journal, 438, 2, pp369 - 378, ISSN/ISBN: 0264-6021
- Mody, N., Agouni, A., McIlroy, GD., Platt, B. & Delibegovic, M. Susceptibility to diet-induced obesity and glucose intolerance in the APPSWE/PSEN1A246E mouse model of Alzheimer’s disease is associated with increased brain levels of protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4), and basal phosphorylation of S6 ribosomal protein, Article, 2011, Diabetologia, 54, 8, pp2143 - 2151, ISSN/ISBN: 0012-186X
- Agouni, A., Owen, C., Czopek, AJ., Mody, N. & Delibegovic, M. In vivo differential effects of fasting, re-feeding, insulin and insulin stimulation time course on insulin signaling pathway components in peripheral tissues, Article, 2010, Biochemical and Biophysical Research Communications, 401, 1, pp104 - 111, ISSN/ISBN: 0006-291X
- Preitner, F., Mody, N., Graham, TE., Peroni, OD. & Kahn, BB. Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis, Article, 2009, American Journal of Physiology: Endocrinology and Metabolism, 297, 6, ppE1420 - E1429, ISSN/ISBN: 0193-1849
- Delibegovic, M. & Mody, N. Protein Tyrosine Phosphatase 1B (PTP1B) in obesity and type 2 diabetes., Article, 2009, Acta Medica Saliniana, 38, 1, pp2 - 7, ISSN/ISBN: 0350-364X
- Mody, N., Graham, TE., Tsuji, Y., Yang, Q. & Kahn, BB. Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice, Article, 2008, American Journal of Physiology: Endocrinology and Metabolism, 294, 4, ppE785 - E793, ISSN/ISBN: 0193-1849
- Delibegovic, M., Bence, KK., Mody, N., Hong, E., Ko, HJ., Kim, JK., Kahn, BB. & Neelt, BG. Improved glucose Homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B, Article, 2007, Molecular and Cellular Biology, 27, 21, pp7727 - 7734, ISSN/ISBN: 0270-7306
- Yan, Q., Yang, Q., Mody, N., Graham, TE., Hsu, C., Xu, Z., Houstis, NE., Kahn, BB. & Rosen, ED. The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin Resistance, Article, 2007, Diabetes, 56, 10, pp2533 - 2540, ISSN/ISBN: 0012-1797
- Yang, Q., Graham, TE., Mody, N., Preitner, F., Peroni, OD., Zabolotny, JM., Kotani, K., Quadro, L. & Kahn, BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes, Article, 2005, Nature, 436, 7049, pp356 - 62, ISSN/ISBN: 0028-0836
- Mody, N., Campbell, DG., Morrice, N., Peggie, M. & Cohen, P. An analysis of the phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (ERK5) by mitogen-activated protein kinase kinase 5 (MKK5) in vitro, Article, 2003, Biochemical Journal, 372, 2, pp567 - 575, ISSN/ISBN: 0264-6021
- Mody, N., Leitch, J., Armstrong, C., Dixon, J. & Cohen, P. Effects of MAP kinase cascade inhibitors on the MKK5/ERK5 pathway, Article, 2001, FEBS Letters, 502, 1-2, pp21 - 24, ISSN/ISBN: 0014-5793
- Mody, N., Hermans, E., Nahorski, SR. & Challiss, RA. Inhibition of N-linked glycosylation of the human type 1alpha metabotropic glutamate receptor by tunicamycin, Article, 1999, Neuropharmacology, 38, 10, pp1485 - 1492, ISSN/ISBN: 0028-3908
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