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Neurovascular Genetics laboratory, Trinity College Dublin

Biographical Information

Dr Matthew Campbell graduated from University College Dublin (UCD) in 2006 with a PhD in Biochemistry followed by Post-doctoral research in Trinity College Dublin (TCD) in Human Molecular Genetics (2006-2012). He has published extensively on the use of RNA interference (RNAi) to modulate levels of distinct tight junction proteins at the blood-brain barrier/inner blood retina barrier (BBB/iBRB) in vivo. Additionally, he has published numerous articles focused on understanding the molecular pathology of diseases such as age-related macular degeneration (AMD), Alzheimer's disease, Schizophrenia, traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).

Research Interests

My laboratory focuses primarily on the molecular biology and physiology of the vasculature associated with neural tissues. We use genetic and molecular biology based approaches to explore the interplay between neural tissues and the systemic circulation. One major topic of my research is centred on the tight junctions located between microvascular endothelial cells of the blood brain and inner blood retina barriers (BBB/iBRB) and how these barriers function in health and disease. We aim to develop technologies to address an unmet clinical need for a range of neural conditions that currently have limited forms of therapeutic intervention and these include Alzheimer Disease, Multiple Sclerosis, Glioblastoma multiforme (GBM), traumatic brain injury (TBI), chronic traumatic encephalopathy.

In addition to translational interests, our lab is also heavily focused on elucidating the under-lying mechanisms of the diseases we are studying and this has led to novel findings associated with the molecular pathology of age-related macular degeneration (AMD) and schizophrenia. Identification of novel therapeutic targets has the potential to rapidly translate to new medicines and this is a strong focus of the lab at present.

Laser induced choroidal neovascularisation (CNV)

Cerebral amyloid angiopathy (CAA) in a human Alzheimer disease (AD) brain

What we work on

RNAi mediated modulation of the BBB and iBRB

We use in vitro and in vivo methods to investigate the role of distinct tight junction proteins in regulating the BBB and iBRB and how these proteins function in health and disease. Given that almost every neurodegenerative condition has BBB dysfunction as a central hallmark or co-morbidity, a greater understanding of the role played by the molecular components of the BBB is essential in identifying novel therapeutic targets for conditions such as Alzheimer Disease (AD), Glioblastoma multiforme (GBM), Multiple sclerosis (MS) and neurotrauma. Modulation of the BBB is also being explored as a strategy to enhance drug delivery to the brain and retina while also being able to alleviate cerebral edema associated with neural malignancies.

Generation of transgenic/knockout mice

In order to better explore the role of distinct components of the BBB/iBRB in mediating the development of a range of neural/ophthalmological conditions, we generate murine models in which we can regulate key components of the tight junctions at the BBB/iBRB. In effect, this allows us to establish disease models to better elucidate the role played by the BBB/iBRB in the development of disease states.

Elucidation of the molecular aetiology of neural diseases

While our lab is heavily focused on translational research and the development of novel therapies for neural conditions, we are actively engaged in research to identify unresolved molecular mechanisms that pre-dispose certain individuals to neural or retinal disease. We are interested in elucidating complex signalling pathways that lead to the development of conditions such as age-related macular degeneration (AMD) a common form of central retinal blindness that can affect almost 1 in 10 individuals over the age of 55. Specifically, we are interested in resolving the role of inflammation in the progression of neural/retinal conditions.

Interested in working with us?

We are always interested in recruiting talented people to the lab and in supporting applications for personal PhD and postdoctoral fellowships.

Please contact Matthew (matthew.campbell@tcd.ie) for further details.

Traumatic Brain Injury (TBI)

Inflammasome oligomerisation in bone marrow derived macrophages

Fundus photograph of a human retina

pTau (green) and claudin-5 (red) staining in a case of chronic traumatic encephalopathy (CTE)

Relevant links

Some Selected Publications:

O’Keeffe, E, Kelly, E, Liu, Y, Giordano, C, Wallace, E, Hynes, M, Tiernan, S, Meagher, A, Greene, C, Hughes, S, Burke, T, Kealy, J, Doyle, N, Hay, A, Farrell, M, Grant, GA, Friedman, A, Veksler, R, Molloy, MG, Meaney, JF, Pender, N, Camarillo, D, Doherty, CP, and *Campbell, M. Dynamic blood brain barrier regulation in mild head trauma. J Neurotrauma, 2019, 5 September 2019

Hudson N, Celkova L, Hopkins A, Greene C, Storti F, Ozaki E, Fahey E, Theodoropoulou S, Kenna PF, Humphries MM, Curtis AM, Demmons E, Browne A, Liddie S, Lawrence MS, Grimm C, Cahill MT, Humphries P, Doyle SL, *Campbell M. Dysregulated claudin-5 cycling in the inner retina causes retinal pigment epithelial cell atrophy. JCI Insight. 2019 Aug 8;4(15).

Farrell M, Aherne S, O'Riordan S, O'Keeffe E, Greene C, Campbell M. Blood-brain barrier dysfunction in a boxer with chronic traumatic encephalopathy and schizophrenia. Clin Neuropathol. 2019 Mar/Apr;38(2):51-58. Clin Neuropathol. 2019 Jan/Feb;38(1):14-22.

Doherty CP , O'Keeffe E, Keaney J, Lawlor B, Coen RF, Farrell M, Campbell M. Neuropolypathology as a result of severe traumatic brain injury? Clin Neuropathol. 2019 Jan/Feb;38(1):14-22.

Greene, C, Kealy, J, et al and Campbell, M. Dose dependent expression of claudin-5 is a modifying factor in schizophrenia. Molecular Psychiatry, 2018 Nov;23(11):2156-2166.

Doherty CP, O'Keefe E, Wallace E, Loftus T, Keaney J, Kealy J, Humphries MM, Molloy MG, Meaney JF, Farrell M, Campbell M. Blood-Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy. J Neuropathol Exp Neurol. 2016 Jul;75(7):656-62.

Keaney J, Walsh DM, O'Malley T, Hudson N, Crosbie DE, Loftus T, Sheehan F, McDaid J, Humphries MM, Callanan JJ, Brett FM, Farrell MA, Humphries P, Campbell M. Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier. Science Advances. (2015) Sep 4;1(8):e1500472.

Keaney J, Campbell M. The dynamic blood-brain barrier. FEBS J. (2015) Nov;282(21):4067-79.

Doyle SL, López FJ, Celkova L, Brennan K, Mulfaul K, Ozaki E, Kenna PF, Kurali E, Hudson N, Doggett T, Ferguson TA, Humphries P, Adamson P, Campbell M. IL-18 Immunotherapy for Neovascular AMD: Tolerability and Efficacy in Nonhuman Primates. Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5424-30.

Doyle, SL, Ozaki, E, Brennan, K, Humphries, MM, Mulfaul, K, Keaney, J, Kenna, PF, Maminishkis, A, Kiang, AS, Saunders, SP, Hams, E, Lavelle, EC, Gardiner, C, Fallon, PG, Adamson, P, Humphries, P, *Campbell, M. IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration. Sci Transl Med. (2014), 2 April, Vol 6, Issue 230. (Reprint, Full Text)

Campbell, M, Hanrahan, F, Gobbo, OL, Kelly, ME, Kiang, AS, Humphries, MM, Nguyen, ATH, Ozaki, E, Keaney, J, Blau, CW, Kerskens, CM, Cahalan, SD, Callanan, JJ, Wallace, W, Grant, GA, Doherty, CP and Humphries, P. Targeted suppression of claudin-5 decreases cerebral edema and improves cognitive outcome following traumatic brain injury. Nature Communications, (2012), May 22;3:849.

Campbell*, M, Doyle*, SL, Ozaki, E, Salomon, RG, Mori, A, Kenna, PF, Kiang, AS, Humphries, MM, Lavelle, EC, O’Neill, LAJ, Hollyfield, JG, and Humphries, P. NLRP3 has a protective role during the development of age related macular degeneration through the induction of IL-18 by drusen components. Nature Medicine (2012) May;18(5):791-8.

Campbell M, Humphries MM, Kiang A-S, Nguyen ATH, Gobbo OL, Tam LCS, Suzuki M, Hanrahan F, Ozaki E, Farrar G-J, Kenna PF, Humphries P. Systemic low molecular weight drug delivery to pre-selected neuronal regions. EMBO Mol Med, (2011), 3:235-245

Campbell, M, Nguyen, ATH, Kiang, AS, Tam, LCS, Gobbo, OL, Kerskens, C, Ni Dhubhghaill, S, Humphries, MM, Farrar, GJ, Kenna, PF, Humphries, P. An experimental platform for systemic drug delivery to the retina. Proc Natl Acad Sci U S A. (2009) Oct 20;106(42):17817-22.

Campbell M, Kiang AS, Kenna PF, Kerskens C, Blau C, O'Dwyer L, Tivnan A, Kelly JA, Brankin B, Farrar GJ, Humphries P. RNAi-mediated reversible opening of the blood-brain barrier. J Gene Med. (2008). Aug;10(8):930-47.