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About Daniel Hardy

Dr. Daniel Hardy is an associate professor in the Department of Obstetrics and Gynecology, Western University, researching molecular mechanisms in early development that, when impaired, may predispose children to metabolic deficits and diseases.

Asset Map Keywords: Fetal Development, Metabolism, and Pregnancy --> (see more)
Children's Health Collaborators: Frank Beier, Edith Arany, Dr. Steve Laviolette, Dr. Michele Mottola (CHRI), and Kat Willmore (CHRI).


The goal of Dr. Hardy's research is to better understand the underlying causes, including environmental and nutritional factors, leading to impaired fetal development and how those causes are linked to greater susceptibility to long-term adverse metabolic outcomes.


Dr. Daniel B. Hardy is an Associate Professor in the Departments of Ob/Gyn and Physiology & Pharmacology. He is also a Scientist with the Children’s Health Research Institute (CHRI).  Dr. Hardy, born and raised in London, completed his BSc (Co-Op Biology) in 1997 from the University of Waterloo. In 2003, he obtained his PhD in the area of placental glucocorticoid metabolism within the Department of Physiology at UWO, under the supervision of Dr. Kaiping Yang. His research interests then led him to pursue a postdoctoral fellowship at the University of Texas Southwestern Medical Center at Dallas under the mentorship of Dr. Carole Mendelson whereby he elucidated some of the mechanisms leading to both term and preterm birth in women. Since 2008, Dr. Hardy’s laboratory focuses upon the molecular mechanisms underlying how impaired fetal development can predispose offspring to metabolic deficits in adulthood.  Understanding this is imperative to develop interventions in early life to reduce the incidence and severity of these diseases long-term.  His research group has identified changes in nuclear receptor activity, epigenetic influences (e.g. posttranslational histone modifications, microRNAs) and endoplasmic reticulum (ER) stress stemming from IUGR which lead to altered long-term liver metabolism. Recently his laboratory group has examined how drugs in pregnancy (i.e. nicotine, D9-THC, and SSRI’s) impact long-term metabolism in the offspring. Dr. Hardy has been supported by CIHR, NSERC, CFI, Women’s Development Council, and the Molly Towell Perinatal Research Foundation.  In 2011, Dr. Hardy has received the Perkin-Elmer Early Career Award by the Perinatal Research Society and was named Children’s Health Research Institute’s “Scientist of the Year” in 2014.


The main focus of my laboratory is investigating the role of nuclear receptors in fetal programming.  While emerging epidemiological evidence suggests that the risks of adult onset diseases are inversely related to birth weight, very little is known about the genetic and/or epigenetic changes which underlie these alterations in fetal and postnatal development. Numerous animals models including maternal caloric and/or nutrient restriction, along with chemically induced gestational diabetes, hypoxia, LPS-invoked inflammation, glucocorticoid exposure, and decreased dietary protein have broadened our understanding how in utero insults may lead to restricted fetal growth. However, understanding the overall role of transcription factors involved in mediating these developmental abnormalities would provide us with better strategies in preventing the onset of adult diseases in mammals.

Nuclear receptors represent the largest family of transcription factors found in metazoans, binding to steroid hormones, fat-soluble vitamins, along with oxysterols and bile acids from the diet. Although the roles of many nuclear receptors are well defined, very little is known about their function in fetal programming, which leads to permanent changes in physiological and/or metabolic processes in adulthood. In my laboratory, we use 'candidate transcription factor' approaches to examine the roles of lipid-sensing nuclear receptors in various models of fetal programming. One such model includes maternal protein restriction, which leads to lower birth weight, impaired offspring growth, decreased liver to body ratio, and an increase in fetal liver cholesterol concentrations.

To address the molecular mechanisms underlying these ‘programmed' changes in nuclear receptor binding and downstream target genes, we employ chromatin immunoprecipitation (ChIP) in tissues and in cells to examine the in vivo binding of nuclear receptors to their respective promoters throughout fetal development. This helps us identify the crucial subset of lipid-sensing nuclear receptors underlying these fetal programming events. Moreover, the use of ChIP in vivo and in vitro further enhances our understanding of how epigenetic modifications are involved in the coordinated control of gene transcription during normal and abnormal fetal development.


Life has come “full circle” for Dan Hardy, who was born and raised in London.

Since the beginning of his undergraduate Co-Operative training at the University of Waterloo, Dr. Hardy has had a great interest in endocrine-related research including diabetes, and pregnancy. In 2003, he obtained his PhD within the Department of Physiology at UWO, under the supervision of Dr. Kaiping Yang. His PhD focused on the molecular mechanisms governing glucocorticoid metabolism in the human placenta. That same year, his research interests then led him to pursue a postdoctoral fellowship at the University of Texas Southwestern Medical Center in Dallas. Under the leadership of Dr. Carole Mendelson, Dr. Hardy investigated some of the mechanisms involved in the actions of steroid hormone receptors, along with pregnancy and parturition.

Dr. Hardy is delighted to have recently returned to Canada as a Scientist within the Lawson Health Research Institute, and as now as Associate Professor in the Departments of Ob/Gyn and Physiology & Pharmacology. His laboratory revisits his earlier PhD interests examining the molecular mechanisms underlying the ‘fetal origins of adult onset diseases (e.g. type II diabetes and cardiovascular disease)’, with support from CIHR, NSERC, Molly Towell and SickKids Hospital Foundation.

Dr. Hardy has received numerous awards for his research including the Endocrine Scholars Award (Endocrine Society), the Perkin-Elmer Early Career Award (PRS), and the Alumni of Honour Award (University of Waterloo). In addition to research, he is the incoming 2016 President of the Irish Benevolent Society of London and Middlesex (est. 1877). Last year Dr. Hardy research was recognized with a “Scientist of the Year Award” from the Children’s Health Research Institute (CHRI).

Research Interest Area: Reproduction and pregnancy; Cardiovascular and vascular health; Children's health

Research Overview
Dr. Hardy has a keen interest in the Developmental Origins of Health and Disease (DOHaD) hypothesis that impaired fetal development can predispose to metabolic diseases in children and adulthood. Although there is strong epidemiological evidence for DOHaD, the underlying molecular mechanisms are poorly understood. This is imperative to develop interventions in early life to reduce the incidence and severity of these diseases in children and adults.

Dr. Hardy has utilized several rodent models of intrauterine growth restriction (IUGR) to elucidate how changes in nuclear receptor activity, epigenetic influences (e.g. posttranslational histone modifications, microRNAs) and endoplasmic reticulum (ER) stress influence long-term metabolism and aspects of the metabolic syndrome.

Collectively, his publications illustrate how postnatal catch-up growth exacerbates these metabolic deficits, which has great implications on clinical practice and upon the management of low birth weight babies.

Keywords: DOHaD, Epigenetics, Metabolism, Placenta

Positions

Present Associate Professor, Western University Department of Obstetrics and Gynaecology
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Present Associate Professor and Assistant Chair, Western University Department of Physiology and Pharmacology
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Present Scientist, Lawson Health Research Institute ‐ Children's Health Research Institute (CHRI)
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Curriculum Vitae




Grants

2022 - 2027 The adverse Impact of Prenatal Cannabinoid Exposure on Placental and Postnatal Cardiovascular Function: Can we Intervene?
Canadian Institutes for Health Research
Project Grant
Role: co-PI
Colleague(s): David Natale
2021 - 2026 Mitochondrial dysfunction: A major player in hepatic development, function, and senescence
Natural Science and Engineering Council of Canada
Discovery Grant
Role: PI
2019 - 2022 The Impact of Perinatal 9-tetrahydrocannabinol (9-THC) Exposure on Long-term Cardiovascular Function in the Offspring
Heart and Stroke Foundation Canada
Grant-in-Aid
Role: PI
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Honors and Awards

  • Recipient of the Western Faculty Scholar Award (2022)
  • Recipient of the LHRI Dr. Joseph Gilbert Contribution of the Year Award (2022)
  • Recipient of the CHRI Scientist of the Year Award (2014)
  • Recipient of the Perinatal Research Society Perkin-Elmer Early Career Award (2011)
  • Recipient of the University of Waterloo Faculty of Science Alumni of Honour Award (2007)
  • Recipient of the Endocrine Scholar Award (2006)

Courses

  • Medical Physiology/P2
  • Human Physiology (Physiology 3120)
  • Fetal Physiology (Physiology 4700b)

Education

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1997 - 2003 PhD, Western University ‐ Department of Physiology and Pharmacology
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1992 - 1997 BSc (Honours Co-operative), University of Waterloo ‐ Biology
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Recent Works (22)