David Hill

Genetics & Development Dr. David Hill
Associate Scientist
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Affiliations

Associate Scientist, Division of Genetics & Development, Children's Health Research Institute
Scientific Director, Lawson Health Research Institute
Integrated Vice-President, Research, London Health Sciences Centre & St. Joseph’s Health Care London
Professor, Department of Medicine, Physiology & Paediatrics, Schulich School of Medicine & Dentistry, Western University
Lawson Professor of Diabetes Research, Lawson Health Research Institute
Sheldon Weinstein Chair of Diabetes Research, Western University

How my research helps children

Research is focused on 1) understanding the mechanisms by which the prenatal and neonatal environment impacts the development of the metabolic axis, and increases the risk of diabetes in adulthood; 2) strategies for inducing beta cell regeneration to reverse juvenile diabetes; and 3) clinical studies in pre-diabetic, obese adolescents to reduce the future risk of type 2 diabetes and vascular disease. Animal models of prenatal programming of postnatal disease include administration of a low protein diet during pregnancy to reproduce intrauterine growth retardation, while mice carrying genetic cell lineage tags are used to demonstrate beta cell regeneration from precursor cells. Intervention studies in obese youth include the combination of pharmacologic and lifestyle parameters.

Research

Current Research Activities

Current research includes investigating the ability to manipulate stem cells to become beta cells.  Beta cells, which reside in the pancreas, are critical to maintaining our health.  In a person without diabetes, beta cells deliver stored and manufactured insulin in the right amount at the right time to keep blood sugars normal.  In type 1 diabetes, beta cells eventually produce no insulin at all.  In type 2 diabetes, the beta cell is working overtime, stressed because of insulin resistance in surrounding muscle and fat cells.

If successful at manipulating stem cells to become beta cells, this could increase the supply of tissue available for human islet transplantation in patients with type 1 diabetes, and also the possibility of inducing targeted regeneration of new beta cells within the pancreas removing the need for transplantation.  Other projects include determining why low birth weight is a major risk factor for type 2 diabetes in adulthood, and the ways in which environmental factors, such as nutrition might trigger or protect against diabetes.

Research Team

Dr. Hill’s lab consists of three graduate students and a research technician.
He has mentored 14 postdoctoral fellows and trained 17 graduate students during his career.

Future Research Plans

The major focus of pre-clinical studies will be on strategies for beta cell regeneration through an understanding of the cellular environment, or niche, that would be optimal for beta cell generation from precursors, including multi-potential stem cells. Particular emphasis will be given to angiogenesis in the islet microvasculature as a trigger for expansion of beta cell mass. These concepts will be tested immediately in a clinical context in randomized trials with new onset type 1 diabetics using known angiogenic drugs. Intervention trials are already in progress to prevent the onset of gestational diabetes in women at risk, and to reduce the risk of type 2 diabetes in obese children. These studies involve partnerships with clinical investigators in the Department of Paediatrics, with the Faculty of Health Sciences, and within a pan-European consortium.

Awards & Grants

Awards & Grants

Funding in support of Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention. – Awarded by European Union, Framework 7 Theme-Health

Funding in support of Nature and potential of beta cell progenitors in the pancreas – Awarded by
Alan Thicke Centre for Juvenile Diabetes Research

Funding in support of Control of regeneration of the endocrine pancreas – Awarded by
Canadian Institutes of Health Research

Funding in support of Prevention of Cardiovascular Complications of Diabetes – Awarded by Canadian Institutes of Health Research 

Funding in support of Fetal Growth restriction: Mechanisms and Outcomes – Awarded by
Canadian Institutes of Health Research

Funding in support of Prevention of Type 2 diabetes in an at-risk pediatric population – Awarded by Children’s Health Foundation

Recent Publications

Publications

Relationship between birth weight and metabolic status in obese adolescents
Hill DJ, Prapavessis H, Shoemaker JK, Jackman M, Mahmud FH, Clarson C
ISRN Obesity. 2013; Article ID 490923, 7 pages

DALI: Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention - Design of an European multicentre, randomised trial
Jelsma JGM, Galjaard S, van Poppel MNM, Desoye G, Corcoy R, Devlieger R, van Assche A, Timmerman D, Harreiter J, Kautzky-Willer A, Damm P, Mathiesen E, Møller Jensen D, Andersen L, Dunne F, Lapolla A, Di Cianni G, Bertolotto A, Wender-Oegowska E, Zawiejska A, Blumska K, Hill DJ, Rebollo P, Snoek FJ, Simmons D
BMC Pregnancy Childbirth. 2013; 13:142

The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes
Hill T, Krougly O, Nikoopour E, Bellemore S, Lee-Chan E, Fouser LA, Hill DJ, Singh B
Cell Regeneration. 2013; 2:2

Cellular mechanisms underlying failed β-cell plasticity in offspring of protein restricted pregnant mice
Cox AR, Beamish C, Carter D, Arany EJ, Hill DJ
Exp Biol Med. 2013; 238:1147-1159

Gestational diabetes mellitus in Europe: prevalence, current screening practice and barriers to screening. A review
Buckley BS, Harreiter J, Damm P, Corcoy R, Chico A, Simmons D, Vellingaand A, Dunne F (on behalf of the DALI Core Investigator Goup)
Diabetic Medicine. 2012; 29:844-854

Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention
Desoye G, Simmons D, Corcoy R, Kautzky-Willer A, van Assche A, Damm P, Mathiesen M, Møller Jensen D, Lotte Andersen L, Dunne F, Lapolla A, Bertolotto A, Snoek F, van Poppel M, Wender-Ozegowska E, Zawiejska A, Hill DJ, Rebollo P, Devlieger R, Timmerman D
Diabetologe. 2012; 8:647–651

Protein restriction during early life in rats alters pancreatic GABAa receptor subunit expression and glucagon secretion in adulthood
Durst MA, Lux-Lantos VA, Hardy DB, Hill DJ, Arany EJ
Canadian J Diabetes. 2012; 36:101-108

Associations of body mass index (BMI) and gestational diabetes mellitus (GDM) with neonatal and maternal pregnancy outcomes in a multicentre European database
Vellinga A, Zawiejska A, Harreiter J, Buckley BS, Di Cianni G, Lapolla A, Corcoy R, Simmons D, Adelantado JM, Damm P, Desoye G, Devlieger R, Hill DJ, Kautzky-Willer A, Klemetti M, Mathiesen ER, Rebollo P, Snoeck F
ISRN Obesity Article ID 424010, pp1-4; (2012) (DALI)

Targeted inhibition of calpain reduces myocardial hypertrophy and fibrosis in mouse models of type-I diabetes.
Li Y, Zhu H, Singh M, Hill DJ, Greer P, Arnold JM, Abel ED, Peng T
Diabetes. 2011; 60:2985-94

Nutritional programming of pancreatic -cell plasticity
Hill DJ
World Journal of Diabetes. 2011; 2:119-132

Use of imaging biomarkers to assess perfusion and glucose metabolism in the skeletal muscel of dystrophic mice
Ahmad N, Welch I, Grange R, Hadway J, Dhanvantari S, Hill DJ, Lee T, Hoffman L
BMC Musculoskeletal Disorders. 2011; 12:127 [E-pub ahead of print]

The effects of atorvastatin on the regeneration of pancreatic beta cells after streptozotocin treatment in the neonatal rodent
Marchand KC, Arany EJ and Hill DJ
American J Physiology - Endocrinology and Metabolism. 2010 Apr 13 [E-pub ahead of print]

The effects of low protein during gestation on mouse pancreatic development and ß-cell regeneration
Cox AR, Arany EJ, Hill DJ
Pediatric Research. 2010 Apr 9 [E-pub ahead of print]

Changes in islet micro-vasculature following streptozotocin-induced ß-cell loss and subsequent replacement in the neonatal rat
Nicholson MJ, Arany EJ, Hill DJ
Experimental Biology and Medicine. 2010; 235:189-198

Participation of pancreatic dopamine D2 receptors in insulin secretion and glucose homeostasis
García-Tornadú I, Ornstein A-M, Chamson-Reig A, Wheeler MB, Hill DJ, Arany E, Rubinstein M, Becu-Villalobos D
Endocrinology. 2010; 151:1441-1450

Metformin in combination with structured lifestyle intervention improves body mass index in obese insulin resistant adolescents
Clarson CL, Mahmud FH, Baker JE, Clark HE, McKay WM, Schauteet VD, Hill DJ
Endocrine. 2009; 36:141-146

Impaired vascular function in obese adolescents with insulin resistance
Mahmud FH, Hill DJ, Cuerden M, Clarson CL
J Pediatrics. 2009; 155:678-682

Exposure of the pregnant rat to low protein diet causes impaired glucose homeostasis in the young adult offspring by different mechanisms in males and females
Chamson-Reig A, Thyssen SM, Hill DJ, Arany E
Experimental Biology and Medicine. 2009; 234:[E-Pub]

Additional publications

Contact

Contact

Phone: (519) 646-6100, x64672
Fax: (519) 646-6110
Email: david [dot] hill [at] lhrionhealth [dot] ca
Website: www.lawsonresearch.com

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