Dr Nimesh Mody
Ph.D. Biochemistry, B.Sc. Biochemistry,
Institute of Medical Sciences (room 5.27)
School of Medicine, Medical Sciences & Nutrition
Foresterhill Health Campus
Aberdeen AB25 2ZD
Current position: Senior Lecturer - since Aug 2017.
Aberdeen Cardiovascular & 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 - University of Dundee, MRC Protein Phosphorylation Unit Oct 1999 - Jul 2003. Specialising in cell signalling, protein phosphorylation of kinases (in particular the MKK5-ERK5 pathway). Supervisor : Prof. Sir Philip Cohen.
- PhD Biochemistry2003 - University of Dundee
- BSc Biochemistry1998 - University College LondonFirst Class Honours.
Memberships and Affiliations
- Internal Memberships
qPCR Facility Academic Lead and member of Core Facilities committee. Part of the IMS Technology Hub.
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.
- External Memberships
- 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.
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
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.
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.
- Glucose and lipid homeostasis - Prof. Mirela Delibegovic
- Retinoic acid signalling in the CNS - Prof. Peter McCaffery
- Mouse models of Alzheimer's disease - Prof. Bettina Platt
- Prof. Lora Heisler, and Dr. Justin Rochford recently joined us from the University of Cambridge, School of Biological Sciences
- Caloric restriction to promote healthy ageing - Prof. Colin Selman (now Uni. of Glasgow)
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
- 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
Funding and 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)
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
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).
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).
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.
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High-fat diet exacerbates cognitive and metabolic abnormalities in neuronal BACE1 knock-in mice - partial prevention by FenretinideNutritional Neuroscience, vol. 25, no. 4, pp. 719-736Contributions to Journals: Articles
Design, synthesis, radiosynthesis and biological evaluation of Fenretinide analogues as anticancer and metabolic syndromepreventive agentsChemMedChem, vol. 15, no. 16, pp. 1579-1590Contributions to Journals: Articles
Effects of Liraglutide and Fenretinide treatments on the diabetic phenotype of neuronal human BACE1 knock-in miceBiochemical Pharmacology, vol. 166, pp. 222-230Contributions to Journals: Articles
Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity Is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon TreatmentJournal of Clinical Medicine, vol. 7, no. 2, 36Contributions to Journals: Articles
Response to comment by Moxon et alClinical Science, vol. 132, no. 1, pp. 39-41Contributions to Journals: Letters
Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute LeukemiaCancer Research, vol. 78, no. 1, pp. 75-87Contributions to Journals: Articles
Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistanceProceedings of the Nutrition Society, vol. 76, no. 4, pp. 597-602Contributions to Journals: Articles
Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR-/- mouse model of atherosclerosisClinical Science, vol. 131, no. 20, pp. 2489-2501Contributions to Journals: Articles
Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE−/− mouse model of atherosclerosis with alterations in IL10/AMPKα pathwayMolecular Metabolism, vol. 6, no. 8, pp. 845-853Contributions to Journals: Articles
Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in miceScientific Reports, vol. 7, 43782Contributions to Journals: Articles
Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J miceScientific Reports, vol. 7, pp. 1-10Contributions to Journals: Articles
Oxidative costs of reproduction in mouse strains selected for different levels of food intake and which differ in reproductive performanceScientific Reports, vol. 6, 36353Contributions to Journals: Articles
Methionine restriction improves renal insulin signalling in aged kidneysMechanisms of Ageing and Development, vol. 157, pp. 35-43Contributions to Journals: Articles
Neuronal human BACE1 knock-in induces systemic diabetes in miceDiabetologia, vol. 59, no. 7, pp. 1513-1523Contributions to Journals: Articles
Elevated fibroblast growth factor 21 (FGF21) levels in obese, insulin resistant states are normalised by fenretinide treatment via retinoic acid signallingDiabetic Medicine, vol. 33, pp. 48Contributions to Journals: Abstracts
Investigation of a Type 2 diabetes-like phenotype in a mouse model of Alzheimer's diseaseDiabetic Medicine, vol. 33, no. Suppl. 1, pp. 82Contributions to Journals: Abstracts
Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissueBiochemical Pharmacology, vol. 100, pp. 86-97Contributions to Journals: Articles
Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signalingObesity, vol. 23, no. 8, pp. 1655-1662Contributions to Journals: Articles
Comparison between beneficial effects of leucine and methionine restriction on regulation of body mass, adiposity, glucose and lipid homeostasisDiabetic Medicine, vol. 32, no. S1, pp. 47-47Contributions to Journals: Abstracts
Mechanisms of improved glucose homeostasis by the synthetic retinoid fenretinide: altered genes, metabolites and lipidsDiabetic Medicine, vol. 32, no. S1, pp. 47-48Contributions to Journals: Abstracts
Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in miceMetabolism, vol. 64, no. 2, pp. 305-314Contributions to Journals: Articles
Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1BDiabetes & Metabolism, vol. 41, no. 1, pp. 95-101Contributions to Journals: Articles
Hepatic protein tyrosine phosphatase 1B (PTP1B) deficiency protects against obesity-induced endothelial dysfunctionBiochemical Pharmacology, vol. 92, no. 4, pp. 607-617Contributions to Journals: Articles
The mechanisms of Fenretinide-mediated anti-cancer activity and prevention of obesity and type-2 diabetesBiochemical Pharmacology, vol. 91, no. 3, pp. 277-286Contributions to Journals: Articles
Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21Aging Cell, vol. 13, no. 5, pp. 817-827Contributions to Journals: Articles
Myeloid-Cell Protein Tyrosine Phosphatase-1B Deficiency in Mice Protects Against High-Fat Diet and Lipopolysaccharide-Induced Inflammation, Hyperinsulinemia, and Endotoxemia Through an IL-10 STAT3-Dependent MechanismDiabetes, vol. 63, no. 2, pp. 456-470Contributions to Journals: Articles
Inducible Liver-Specific Knockdown of Protein Tyrosine Phosphatase 1B Improves Glucose and Lipid Homeostasis in Adult MiceDiabetologia, vol. 56, no. 10, pp. 2286-2296Contributions to Journals: Articles
High fat diet-induced deterioration of cognitive deficits in hBACE1 knock-in mouse model of Alzheimer’s disease, reversal by anti-obesity, anti-diabetes compound MN101British Neuroscience Association FestivalContributions to Conferences: Posters
BACE1: The missing link between Alzheimer’s disease, diabetes and obesity?Alzheimer Research UKContributions to Conferences: Posters
BACE1: the missing link between Alzheimer's disease, diabetes and obesity?Alzheimer Research UKContributions to Conferences: Posters
Fenretinide Treatment Prevents Diet-Induced Obesity in Association With Major Alterations in Retinoid Homeostatic Gene Expression in Adipose, Liver and HypothalamusDiabetes, vol. 62, no. 3, pp. 825-836Contributions to Journals: Articles
PTP1B in the periphery: regulating insulin sensitivity and ER stressProtein tyrosine phosphatase control of metabolism. Bence, K. K. (ed.). Springer, pp. 91-105, 15 pagesChapters in Books, Reports and Conference Proceedings: Chapters
Optoelectronic tweezers for the measurement of the relative stiffness of erythrocytesChapters in Books, Reports and Conference Proceedings: Conference Proceedings
(18) Fenretinide treatment for high fat diet-induced obesity and insulin sensitivityAtherosclerosis, vol. 223, no. 2, pp. 532Contributions to Journals: Articles
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 genesInternational Journal of General Medicine, vol. 5, pp. 403-411Contributions to Journals: Articles
Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasisPloS ONE, vol. 7, no. 2, e32700Contributions to Journals: Articles
Liver-specific deletion of protein tyrosine phosphatase (PTP) 1B improves obesity- and pharmacologically induced endoplasmic reticulum stressBiochemical Journal, vol. 438, no. 2, pp. 369-378Contributions to Journals: Articles
Susceptibility to diet-induced obesity and glucose intolerance in the APP (SWE)/PSEN1 (A246E) 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 proteinDiabetologia, vol. 54, no. 8, pp. 2143-2151Contributions to Journals: Articles
In vivo differential effects of fasting, re-feeding, insulin and insulin stimulation time course on insulin signaling pathway components in peripheral tissuesBiochemical and Biophysical Research Communications, vol. 401, no. 1, pp. 104-111Contributions to Journals: Articles
Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosisAmerican Journal of Physiology: Endocrinology and Metabolism, vol. 297, no. 6, pp. E1420-E1429Contributions to Journals: Articles
Protein Tyrosine Phosphatase 1B (PTP1B) in obesity and type 2 diabetesActa Medica Saliniana, vol. 38, no. 1, pp. 2-7Contributions to Journals: Articles
Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob miceAmerican Journal of Physiology: Endocrinology and Metabolism, vol. 294, no. 4, pp. E785-E793Contributions to Journals: Articles
Improved glucose Homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1BMolecular and Cellular Biology, vol. 27, no. 21, pp. 7727-7734Contributions to Journals: Articles
The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin ResistanceDiabetes, vol. 56, no. 10, pp. 2533-2540Contributions to Journals: Articles
Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetesNature, vol. 436, no. 7049, pp. 356-62Contributions to Journals: Articles
An analysis of the phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (ERK5) by mitogen-activated protein kinase kinase 5 (MKK5) in vitroBiochemical Journal, vol. 372, no. 2, pp. 567-575Contributions to Journals: Articles
Effects of MAP kinase cascade inhibitors on the MKK5/ERK5 pathwayFEBS Letters, vol. 502, no. 1-2, pp. 21-24Contributions to Journals: Articles
Inhibition of N-linked glycosylation of the human type 1alpha metabotropic glutamate receptor by tunicamycin: effects on cell-surface receptor expression and functionNeuropharmacology, vol. 38, no. 10, pp. 1485-1492Contributions to Journals: Articles