Dr Jacob H. Hollis

Research Officer - Department of Physiology

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Education and Work Experience

Research Interests

Jacob’s thesis was titled The Signaling of Acute and Chronic Immune Activation to the Central Nervous System.  His Ph.D. studies focused on the mechanisms through which the immune system signals to the brain and activates brainstem catecholaminergic and serotonergic systems and how these interactions regulate physiology and behavior.  Jacob’s work included acute models of infection using lipopolysaccharide (endotoxin from E. coli) and chronic models of infection using a virulent human strain of M. tuberculosis.  Jacob is now working with Professor Oldfield in the Metabolic Neurosciences Group of the Department of Physiology, expanding his research interests to also include the regulation of metabolism and glucose homeostasis through immune-endocrine-brain communication.

Research Projects

Jacob is involved in a number of ongoing research projects:

Cytokines on the brain? Understanding the interactions between cytokines and neuropeptides which regulate metabolism during infection
Chronic illnesses such as cancer and AIDS are associated with anorexia and cachexia (muscle wasting) which are debilitating side effects that reduce quality of life.  Pro-inflammatory cytokines (IL-1β, TNF-α) are responsible for the range of physiological and behavioural changes that are collectively referred to as ‘sickness’.  Ant-inflammatory cytokines (IL-10) are also produced in response to infection and act as endogenous ‘brakes’, ensuring survival.  The interaction of pro- and anti-inflammatory cytokines at the level of the brain modulates neuropeptide expression and secretion, subsequently regulating metabolism.  This project investigates the central actions of both pro- and anti-inflammatory cytokines and the role of neuropeptide systems during models of acute infection and the metabolic consequences of these interactions.  The neural systems of interest include the neuropeptide Y, melanocyte stimulating hormone, orexin, and melanin concentrating hormone systems of the hypothalamus.  The project involves surgical procedures such as implantation of cerebral cannula and telemetric devices, physiological measurements such as telemetric recording of body temperature and indirect calorimetry, and post-hoc analysis of tissue that includes immunohistochemistry and quantitative real-time PCR.

Have you had your daily recommended dosage of dirt?  Probiotics as a potential therapeutic to alter metabolism and prevent disease
Honours student on project: Toni McGee
In the modern day world we live in, our food comes pre-packaged, sterile, and full of preservatives.  The increased usage of anti-bacterial soaps and household sprays, and the over-prescription of antibiotics, is creating an environment of sterility that we live in and our children are growing up in.  Because the bacterial antigens that we would normally be exposed to, those in the backyard or in the parks, are becoming scarcer, the promotion of probiotics—good bacteria that promote digestive health—are being heavily marketed to the public as a panacea.  Interestingly, very little is actually known about the mechanisms of action of probiotics and the therapeutic potential.  The present project investigates these very important questions about the therapeutic potential of probiotics to modulate aspects of metabolism including appetite, energy expenditure, and the ability to prevent immune-related metabolic diseases such as type-2 diabetes.  The project involves surgical procedures such as implantation of cerebral cannula and telemetric devices, physiological measurements such as telemetric recording of body temperature and indirect calorimetry, and post-hoc analysis of tissue that includes immunohistochemistry and quantitative real-time PCR.

How do endogenous cannabinoids regulate metabolism during infection?  Understanding immune-endocannabinoid interactions within the brain
In collaboration with Assist. Prof. Hossein Jonaidi, University of Kerman
During infection, pro-inflammatory cytokines signal to the brain to activate a range of neuropeptide systems involved in the regulation of metabolism.  Metabolic changes during infection include fever, loss of appetite, and reduced arousal.  The endocannabinoid system includes the endogenous arachidonic acid derivatives anandamide and 2-arachydonoylglycerol (2-AG), and two receptors CB1-R and CB2-R.  Anandamide, 2-AG, and the two receptors are ubiquitously expressed throughout the periphery and central nervous system. CB-1R is involved in aspects of metabolism including appetite and energy expenditure, whereas CB-2R is involved in regulating immune function.  Both of the endocannabinoid receptors seem to stimulate anti-inflammatory signals, but through different mechanisms which are poorly understood.  In addition, the interaction between the immune system and the endocannabinoid system is reciprocal, as the immune system influences the endocannabinoid system.  Because the immune system and the endocannabinoid system are both important in the regulation of metabolism, studies investigating the interactions between these two systems could prove extremely interesting and potentially beneficial for novel therapeutics.  The project involves surgical procedures such as implantation of cerebral cannula and telemetric devices, physiological measurements such as telemetric recording of body temperature and indirect calorimetry, and post-hoc analysis of tissue that includes immunohistochemistry and quantitative real-time PCR.

Cannabinoids and fat; Understanding immune-endocannabinoid interactions in obesity and insulin resistance
In collaboration with Dr. Aaron Verty
Clinical and animal research has produced overwhelming evidence that obesity promotes a state of inflammation.  Obesity-induced inflammation is characterised by the increased production of pro-inflammatory cytokines including tumour necrosis factor-α (TNF-α) as well as the increased production of anti-inflammatory cytokines including IL-10.  Obesity-induced inflammation is associated with a range of intracellular and gene transcription changes that promote insulin resistance.  The endocannabinoid system includes two receptors, CB1-R and CB2-R, both ubiquitously expressed throughout the periphery and central nervous system. CB-1R is involved in aspects of metabolism including appetite and energy expenditure, whereas CB-2R is involved in regulating immune function. The role of CB1-R in the devlopment of obesity, and the therapeutic effects of antagonists for CB1-R, have been studied extensively in recent years.  However no studies have yet investigated the role of CB2-R in the inflammatory aspects of obesity.  The project involves surgical procedures such as implantation of cerebral cannula and telemetric devices, physiological measurements such as telemetric recording of body temperature and indirect calorimetry, and post-hoc analysis of tissue that includes immunohistochemistry and quantitative real-time PCR.

Fat is not just fat?  Central estrogen receptors in regulating metabolism and fat distribution
Ph.D. student on project: Elaine Adler
Abdominal fat which is more developed in males than females is more dangerous because it is the major correlate of metabolic syndrome with all of its pathologies such as heart disease, diabetes, stroke, etc.  Subcutaneous fat on the other hand is far less of a problem and is found more in pre-menopausal women.  The answers to why abdominal fat but not subcutaneous fat correlates well with deadly obesity-related pathologies are not known.  One potential explaination is the central actions of the sex hormone estrogen, as the fat distribution of women changes to a more male-like distribution post-menopause when circulating estrogen levels drop significantly.  In addition, male animals treated with estrogen develop a female compartmentalisation of fat.  As most obesity research has focused on the mechanisms behind the development of obesity and means of reversing obesity, the present project aims to understand the central mechanisms behind the distribution of fat.   The project involves surgical procedures such as implantation of cerebral cannula and telemetric devices, physiological measurements such as telemetric recording of body temperature and indirect calorimetry, and post-hoc analysis of tissue that includes immunohistochemistry and quantitative real-time PCR.

Supervision experience

Teaching Experience

Academic Distinctions, Awards, and Funding

1.      H & L Hecht Trust Fund,Australia.  Equipment for the study of brain regions involved in the sensation of hunger.  Award amount: $36,000 AUD (2006).

2.      Post-graduate student scholarship, provided by Neuroendocrine Charitable Trust, London UK (2000-2005).

3.      BRAIN travel award, provided by BRAIN, London UK (2003).

4.      Accepted attendance and award for best poster presentation at ELBA workshop on HPA axis in stress and disease, Elba, Italy (2002).

5.      Bristol Alumni Travel Scholarship, provided by the Bristol Alumni Foundation, UK (2002).

6.      Hughes Summer Research Assistantship, provided by the Howard Hughes Medical Institute, USA (1997).

Departmental Responsibilities

Publications

1.      J. H. Hollis, M. J. McKinley, M. D’Souza, J. Kampe, B. J. Oldfield (2008).  The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex; a neuroanatomical framework for the generation of thirst.  Am J Physiol Regul Integr Comp Physiol. 294(4):R1390-401.

2.      C. A. Lowry, J. H. Hollis, A. De Vries, B. Pan, L. R. Brunet, R. F. Hunt, J. F. R. Paton, E. Van Kampen, D. M. Knight, A. K. Evans, G. A. W. Rook, S. L. Lightman (2007). Identification of an immune-responsive mesolimbocortical serotonergic system: potential role in regulation of emotional behaviour.  Neurosci. 146:756-772.

3.      J. H. Hollis, A. K. Evans, K. P. E. Bruce, S. L. Lightman, C. A. Lowry (2006). Lipopolysaccharide has indomethacin-sensitive actions on Fos expression in topographically organized subpopulations of serotonergic neurons. Brain Behav Immun. 20: 569-577.

4.      J. H. Hollis, S. L. Lightman, C. A. Lowry (2005). Lipopolysaccharide has selective actions on sub-populations of catecholaminergic neurons involved in activation of the HPA axis and inhibition of prolactin secretion. J Endocrinol. 184(2): 393-406.

5.      P. J. Johnson, J. H. Hollis, R. Moratalla, S. L. Lightman, C. A. Lowry (2005). Acute hypercarbic gas exposure reveals functionally distinct subpopulations of serotonergic neurons in rats. J Psychopharmacol. 2005 Jul;19(4):327-41. Erratum in: J Psychopharmacol. 2005 Sep;19(5):561.

6.      J. H. Hollis, S. L. Lightman, C. A. Lowry (2004). Integration of systemic and visceral sensory information by medullary catecholaminergic systems during peripheral inflammation. Ann N Y Acad Sci 1018: 71-75.

7.      J. K. Abrams, P. J. Johnson, J. H. Hollis, C. A. Lowry (2004). Anatomic and functional topography of the dorsal raphe nucleus. Ann N Y Acad Sci 1018: 46-57.

8.      S.L. Stevens, J. Bao, J. Hollis, N.S. Lessov, W.M. Clark, M.P. Stenzel-Poore (2002).  The use of flow cytometry to evaluate temporal changes in inflammatory cells following focal cerebral ischemia in mice. Brain Res 932(1-2): 110-119.

9.      S.C. Coste, R.A. Kesterson, K.A. Heldwein, S.L. Stevens, A.D. Heard, J. H. Hollis, S.E. Murray, J.K. Hill, G.A. Pantely, A.R. Hohimer, D.C. Hatton, T.J. Phillips, D.A. Finn, M.J. Low, M.B. Rittenberg, P. Stenzel, and M.P. Stenzel-Poore (2000). Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nature Genetics 24(4): 403-409.