Denise Belsham

Research Interests

My research program is divided into three main themes: 1. Control of reproductive neuronal function by nutrients, neuroinflammatory agents, and afferent neuronal input; 2. Central and peripheral mechanisms controlling neuronal cell types expressing neuropeptides linked to the regulation of energy homeostasis; and 3. Circadian control of hypothalamic neuropeptides.

AFFILIATIONS:

Banting and Best Diabetes Centre, University of Toronto
Centre for Research in Women’s Health, University of Toronto
Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto

Professional Memberships

American Neuroendocrine Society
Society for Neuroendocrinology
Physiological Society
Physiological Society
Society for Neuroscience
Society for Endocrinology and Metabolism

Research Synopsis

Research Interests: My research program is divided into three main themes: 1. Control of reproductive neuronal function by nutrients, neuroinflammatory agents, and afferent neuronal input; 2. Central and peripheral mechanisms controlling neuronal cell types expressing neuropeptides linked to the regulation of energy homeostasis; and 3. Circadian control of hypothalamic neuropeptides.

My long-term goal is to understand how the hypothalamus is able to achieve its diverse, but highly integrated control of basic physiological processes. All of the research projects initiated in my laboratory, or through collaborations with other research labs at the University of Toronto or globally, will help to define the molecular mechanisms involved in the neuroendocrine events initiated at the level of the hypothalamus through the analysis of specific cell models.

Keywords: Neuroendocrinology, reproductive biology, gonadotropin-releasing hormone, steroids, melatonin, neuropeptide Y, kisspeptin, phoenixin, neurotensin, proopiomelanocortin, ghrelin, proglucagon-derived peptides, feeding peptides, energy homeostasis, circadian rhythm, receptors, hypothalamus, hormones, insulin, leptin, estrogen, ciliary neurotropic factor, neuronal cell culture, molecular biology, transcription, signal transduction, cell biology.

Detailed Description: My research program currently has three major directions, which are described in more detail below.

Overview of Dr. Belsham’s Research Program: 

The main focus of my laboratory is to understand, at the molecular level, how the hypothalamus achieves its diverse physiological functions. The neuroendocrine hypothalamus consists of a complex array of distinct neuronal phenotypes, each expressing a specific complement of neuropeptides, neurotransmitters and receptors. Many of our vital needs, such as those for growth, reproduction, nutrition, sleep, and stress responses, depend on hormonal balance or homeostasis, which is controlled by both external and internal stimuli or signals at the hypothalamic level.

A) Regulation of GnRH Neurons and Afferent Control Mechanisms: 

In order to begin to dissect the molecular signals responsible for the release of specific peptides from individual hypothalamic neurons, my laboratory has focussed on the peptide that controls reproduction, gonadotropin-releasing hormone or GnRH. A large number of neuromodulators have been implicated in the control of reproductive function, as they have been found to regulate GnRH synthesis and secretion. My research program studies many aspects of GnRH function, and how afferent neurons affect the GnRH neurons. We also study the direct regulation of these afferent neurons, such as kisspeptin, neuropeptide Y, phoenixin, and gonadotropin inhibitory hormone, by hormones, nutrients, and other peripheral signals.

B) Generation and Characterization of Novel Hypothalamic Cell Models: 

We therefore analyze the direct actions of neuromodulators on individual GnRH neurons; the transcriptional mechanisms dictating the neurogenesis of individual hypothalamic neurons; and the development of specific immortalized hypothalamic neuronal cell models in order to understand the molecular mechanisms involved in interneuron communication and signaling. To address this last point, my laboratory generates a number of cell models representing specific cell types from the hypothalamus. These models have been used by many labs worldwide to understand how hypothalamic neurons function. These models include embryonic- and adult-derived cell models from the mouse and rat, and represent the many cell types found in the hypothalamus and hippocampus.

C) Analysis of the Neuropeptides involved in Energy Homeostasis: 

We have a strong track record of neuroendocrine research, and have also expanded our research program to include the study of neuropeptides involved in both reproduction and energy homeostasis. Currently half of my research efforts are directed towards studies related to the function of the GnRH and afferent neurons, such as kisspeptin, neuropeptide Y, phoenixin and gonadotropin inhibitory hormone, and the other half has extended our research program to include studies of many of the neuropeptide-expressing neurons involved in energy homeostasis. These include neuropeptide Y, neurotensin, brain ghrelin, corticotropin-releasing hormone, and proopiomelanocortin. We are currently analyzing the changes in gene expression and signal transduction events after exposure to key peripheral signals such as insulin, ghrelin, glucose, leptin, and estrogen. We also study the mechanisms involved in neuroinflammatory signal transduction induced by exposure of neurons to excess nutrients, such as saturated fatty acids and high glucose. Importantly, there is also a direct relationship between nutritional status and reproduction, therefore my research program is poised to utilize all the information gained to provide insight into the complex nature of integrated neuroendocrine control of basic physiology.

METHODS USED

Brain Slice, Neurons, Pancreas Cells,

Procedures: Elisa, gene expression analysis, immunohistochemistry, immunocytochemistry, in vivo hypothalamus immunocytochemistry, microarrays, molecular and cellular biology techniques, proteomics, qRT-PCR, retroviral and lentiviral transfections, RIA, RT-PCR, signal transduction characterization, siRNA, stereotaxic brain surgery, western blot.

EQUIPMENT USED

Analytical Balances, Benchtop Centrifuge, Blotting Apparatus, Confocal Microscope, Culture Hood, Culture Incubators, Cryostat, Departmental Beta and Gamma Counters, Dissecting Microscope, Fluorescence Microscope, Fresh Tissue Sectioning systems, Gel Apparatus, Low and high speed centrifuge, Low and Ultralow Freezers, Microwave Oven, Mini Vortexer, Plate reader, ProBlot Hybridization Oven, Real-Time/Thermocycler. Setups for Electropherosis, Stirrer/Hot Plate, Water baths

PRESENT TRAINEES

Neruja Loganathan – Post-doctoral Fellow
Emma McIlwraith - PhD student 
Calvin Lieu - PhD student 
Ishnoor Singh - PhD student  
Kimberly Mak - MSc student 
Wenyuan (Kevin) He - Undergraduate student
Ningtong (Yolanda) Zhang - Undergraduate student
Kun Oh - Undergraduate student
Aws Mustafa - Undergraduate Student
Hao Han (Horman) Qian - Undergraduate student
Vanessa Nkechika - Undergraduate student
Andre Krunic - Undergraduate student
Andy Tran – Research Assistant

PRESENT COLLABORATIONS

Within the Department of Physiology:
Michael Wheeler
Patricia Brubaker

Recent Publications

http://www.ncbi.nlm.nih.gov/pubmed/25519730

Appointments

Cross Appointed to Medicine, Ob/Gyn

Courses

Course Number: PSL 1000/2000 (Director); PSL 4050 (Director); PSL 1034; PSL 1075; PSL 424 (Director); PSL 450; PSL 498/499; ROP 299/399; PSL 1066