Jean-François Paré
Paré co-authored a study of an ion channel in left-right body patterning12. Paré was first author of a study of membrane voltage and resistance to infection345. Paré also co-authored work on how the developing brain shapes innate immunity6. Later reviewers cite the last two together7.
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Channels and left-right asymmetry
In a 2017 paper with Pai, Levin and others, Paré was one of the co-authors on work about the HCN4 channel in Xenopus. The authors tested whether blocking HCN4 randomises organ position by disturbing the sidedness of the Nodal, Lefty and Pitx2 cascade2. They also injected at later cleavage stages. The effect depended on timing: the channel's activity had to act very early in cleavage to matter for heart and visceral organ laterality1.
Voltage and resistance to infection
Paré, Martyniuk and Levin (2017) used Xenopus embryos to ask how membrane voltage affects innate immunity. The embryos make no mature B or T cells until 12 days after fertilisation, so innate defences act alone3. Hyperpolarising the host with potassium channels lowered survival after infection4. Blocking serotonin transport reduced or removed the gain in resistance seen with depolarisation, which pointed to a serotonin pathway5.
Brain, immunity and later use
In 2020 Herrera-Rincon, Paré and colleagues used embryos whose brain was removed early, though the animals stayed alive and kept developing6. They used this model to study the brain's role in early innate immunity, with and without infection. McMillen and colleagues later cited this work and the 2017 immune paper together. They read both as evidence that bioelectric or central nervous system manipulation can alter macrophage behaviour, and suggested testing it in metastasis7.
We conclude that HCN4 channel activity is involved in determining heart and visceral organ laterality; moreover, its activity must occur very early during cleavage stages
Pai VP, Willocq V, Pitcairn EJ, Lemire JM, Paré JF, Shi NQ…, 2017 · HCN4 ion channel function is required for early events that regulate anatomical… · open at passage 12Thus, we asked if HCN4 channel inhibition induces randomization by perturbing the normally consistent sidedness of this transcriptional cascade.
Pai VP, Willocq V, Pitcairn EJ, Lemire JM, Paré JF, Shi NQ…, 2017 · HCN4 ion channel function is required for early events that regulate anatomical… · open at passage 14A significant advantage of this model organism with respect to the current study is that during X. laevis development, there are no detectable mature B or T cells until 12 days post-fertilization
Paré JF, Martyniuk CJ, Levin M, 2017 · Bioelectric regulation of innate immune system function in regenerating and… · open at passage 4Overexpression of two hyperpolarizing potassium channels, Kv1.5 and an overactive Kir2.1 mutant,47–49 led to respective significant decreases of 35.3 +/− 17.4 and 39.0 +/− 2.0% in survival after infection
Paré JF, Martyniuk CJ, Levin M, 2017 · Bioelectric regulation of innate immune system function in regenerating and… · open at passage 12expression of the dominant negative serotonin transporter significantly reduced (for ivermectin treatment) or nullified (for BaCl2 treatment) the depolarization-induced increase in the resistance to infection
Paré JF, Martyniuk CJ, Levin M, 2017 · Bioelectric regulation of innate immune system function in regenerating and… · open at passage 19the brain is removed during early embryonic stages, but the animal can be kept alive and development continues.
Herrera-Rincon C, Paré JF, Martyniuk CJ, Jannetty SK…, 2020 · An in vivo brain-bacteria interface: the developing brain as a key regulator of… · open at passage 4there is also a growing body of evidence that bioelectric manipulation either via chemicals (Paré et al., 2017) or removal of central nervous system (Herrera-Rincon et al., 2020) input can alter macrophage behavior
McMillen P, Oudin MJ, Levin M, Payne SL, 2021 · Beyond Neurons: Long Distance Communication in Development and Cancer · open at passage 29
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