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Matt Gill, Ph.D.

Assistant Professor
Department of Metabolism & Aging
Florida Campus
Laboratory Website
mgill@scripps.edu
(561) 228-2954

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Affiliate Research Assistant Professor, Center for Molecular Biology and Biotechnology, Florida Atlantic University

Research Focus

Aging is the single most important factor determining the onset of human disease in developed countries.  With current demographic trends indicating that the number of individuals over the age of 65 in the US will rise from 35 million in the year 2000 (13% of the total population) to 70 million in the year 2030 (1 in 20) it is clear that an understanding of the processes that underpin aging and age-related disease represents a key challenge in the biomedical sciences.  

In recent years there have been huge advances in our understanding of the aging process and many of these have stemmed from genetic analysis of the nematode Caenorhabditis elegans (C. elegans). These studies have identified endocrine signaling pathways conserved between worms and mammals that include receptors whose endogenous ligands are small, lipid-derived hormones that cannot be identified by genetic approaches alone.  These hormone pathways are also tractable drug targets and thus the identification of small molecule regulators of their activity could lead to rational drug development for aging and age-related disease.  Given the conservation of aging pathways between species, this approach is likely to open up new therapeutic avenues for combating human aging and age-related disease. 

My lab uses an interdisciplinary approach that combines chemical screens, analytical chemistry, biochemistry and genetics to identify small molecule regulators of aging in C. elegans and determine their molecular mechanism of action.  Using this approach we have recently identified a group of lipid signaling molecules called N-acylethanolamines (NAEs) in the worm, one of which shows similarity to mammalian endocannabinoids and affects nematode lifespan by modulating pathways involved in nutrient sensing and dietary restriction.  Endocannabinoid pathways in mammals are well known to be involved in nutrient sensing and energy balance but a role in the aging process has not yet been demonstrated.  The discovery of NAEs and endocannabinoids in C. elegans not only provides a means of further investigating the role of these important signaling molecules in lifespan determination but also brings a powerful genetic system to the study of NAE physiology.

Education

B.Sc., Biochemistry, University of Newcastle-upon-Tyne, UK, 1993
Ph.D., Endocrinology, University of Manchester, UK, 1997

Professional Experience

1998–2001 Medical Research Council Training Fellow, University of Manchester, UK
2002-2004 Brookdale National Fellow, Buck Institute for Research on Aging, Novato, CA
2004-2007 Staff Scientist, Buck Institute for Research on Aging, Novato, CA
2007-2011 Assistant Research Professor, Buck Institute for Research on Aging, Novato, CA

Awards & Professional Activities

1998 - Medical Research Council Research Fellowship
2002 - Brookdale National Fellowship

Selected References

Kaul TK, Reis Rodrigues P, Ogungbe IV, Kapahi P, Gill MS. Bacterial fatty acids enhance recovery from the dauer larva in Caenorhabditis elegans.  PLOS One 2014 9(1):e86979

Katewa SD, Demontis F, Kolipinski M, Hubbard A, Gill MS, Perrimon N, Melov S, Kapahi P. Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster.  Cell Metab 2012 16(1):97-103

Lucanic ML, Held JM, Vantipalli MC, Klang IM, Graham JB, Gibson BW, Lithgow GJ, Gill MS. N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans. Nature 2011 473 (7346):226-9

Comment in
De Petrocellis L and Di Marzo V. Cell signaling: Why fasting worms age slowly. Nature 2011 473(7346):161-3

Benedetti MG, Foster AL, Vantipalli MC, White MP, Sampayo JN, Gill MS, Olsen A, Lithgow GJ. Compounds that confer thermal stress resistance and extended lifespan. Exp Gerontol 2008 43(10):882‐91

Held JM, White MP, Fisher AL, Gibson BW, Lithgow GJ, Gill MS. DAF‐12‐dependent rescue of dauer formation in C. elegans by 25S‐cholestenoic acid. Aging Cell 2006 5(4):283‐91

Gill MS, Held JM, Fisher AL, Gibson BW, Lithgow GJ. Lipophilic regulator of developmental switch in Caenorhabditis elegans. Aging Cell 2004 Dec;3(6):413‐21

Gill MS, Olsen A, Sampayo JN, Lithgow GJ. An automated high‐throughput assay for survival of the nematode Caenorhabditis elegans. Free Radic Biol Med. 2003 35(6): 558‐65

Barreto‐Filho JA, Alcantara MR, Salvatori R, Barreto MA, Sousa AC, Bastos V, Souza AH, Pereira RM, Clayton PE, Gill MS, Aguiar‐Oliveira MH. Familial isolated growth hormone deficiency is associated with 4 increased systolic blood pressure, central obesity, and dyslipidemia. J Clin Endocrinol Metab 2002 87(5):2018‐23

MS Gill, V Tillmann, JD Veldhuis & PE Clayton. Patterns of GH output and their synchrony with short‐term height increments influence stature and growth performance in normal children. Journal of Clinical Endocrinology & Metabolism 86:5860‐3, 2001

S Melov, J Ravenscroft, S Malik, M Gill, D Walker, P Clayton, D Wallace, B Malfroy, S Doctrow, G Lithgow. Extension of lifespan with superoxide dismutase/catalase mimetics. Science 289: 1567‐1569, 2000

MH Aguiar‐Oliveira, MS Gill, ES de A Barretto, MRS Alcântara, F Miraki‐Moud, CA Menezes, AHO Souza, CE Martinelli, FA Pereira, R Salvatori, MA Levine, SM Shalet, C Camacho‐Hubner, PE Clayton. Effect of Severe Growth Hormone Deficiency due to a Mutation in the Growth Hormone Releasing Hormone Receptor on the Insulin‐like Growth Factors (IGFs), IGF Binding Proteins and Ternary Complex Formation Throughout Life. Journal of Clinical Endocrinology & Metabolism, 1999, 84:4118‐4126

ES de A Barreto, MS Gill, MH Aguiar‐Oliveira, CA Menezes, AHO Souza & PE Clayton. Serum Leptin and Body Composition in Children with Familial Growth Hormone (GH) Deficiency due to a Mutation in the Growth Hormone‐Releasing Hormone (GHRH) Receptor. Clinical Endocrinology, 1999, 51: 559‐564

MS Gill, NKS Thalange, PJ Foster, V Tillmann, DA Price, PJ Diggle & PE Clayton. Regular fluctuations in growth hormone (GH) release determine normal human growth. Growth hormone & IGF Research, 1999, 9:114‐122

MS Gill, CM Hall, V Tillmann & PE Clayton. Constitutional delay in growth and puberty is associated with hypoleptinaemia. Clinical Endocrinology, 1999, 50:721‐726

MS Gill, AA Toogood, J Jones, PE Clayton & SM Shalet. Serum leptin response to the acute and chronic administration of Growth Hormone (GH) to elderly subjects with GH deficiency. Journal of Clinical Endocrinology & Metabolism, 1999, 84:1288‐95

MS Gill, AA Toogood, PA O'Neill, MO Thorner, SM Shalet & PE Clayton. Urinary growth hormone (GH), insulin‐like growth factor (IGF)‐I and IGF binding protein‐3 measurements in the diagnosis of adult GH deficiency. Journal of Clinical Endocrinology & Metabolism, 1998, 83:2562‐2565

MS Gill, AA Toogood, PA O'Neill, JE Adams, MO Thorner, SM Shalet & PE Clayton. Relationship between growth hormone (GH) status, serum leptin and body composition in healthy and GH deficient elderly subjects. Clinical Endocrinology, 1997,47, 161‐167

PE Clayton, MS Gill, CM Hall, V Tillman, AJ Whatmore & DA Price. Serum leptin through childhood and adolescence. Clinical Endocrinology, 1997; 46: 727‐733

MS Gill, AJ Whatmore, V Tillman, A White, GM Addison, DA Price & PE Clayton. Urinary IGF and IGF binding protein‐3 in children with disordered growth. Clinical Endocrinology, 1997; 46: 483‐492

NKS Thalange, PJ Foster, MS Gill, DA Price & PE Clayton. Model of normal prepubertal growth. Archives of Diseases in Childhood, 1996; 75: 427 ‐ 431

NKS Thalange, MS Gill, L Gill, AJ Whatmore, GM Addison, DA Price & PE Clayton. Infradian rhythms in urinary growth hormone excretion. Journal of Clinical Endocrinology & Metabolism, 1996; 81: 100‐106

Links

Department of Metabolism & Aging

“Nematodes reveal the secret to a long life”

“New pathway affecting lifespan identified: Discovery advances study of diet and longevity"

Scripps Researcher identifies new pathway affecting lifespan