Speakers
Bruce J Nicholson
Department of Biochemistry and Structural Biology, University of Texas Health San Antonio
Dr. Bruce J. Nicholson, served as the Chair of the Department of Biochemistry and Structural Biology at UT Health San Antonio from 2004-2019, and is co-founder and past director of the Center for Innovative Drug Discovery, a joint venture between UTHealth SA and UTSA that provides High Throughput Screening and Medicinal Chemistry expertise and facilities to Southern Texas. He is also a co-founder of Hera Biotech.
Dr. Nicholson, a native of Australia, obtained his PHD and post-doctoral training at the California Institute of Technology before taking his first faculty position at the University at Buffalo, SUNY. There he served as the Director of the Center for Advanced Molecular Biology and Immunology for 8 years, founding the first interdisciplinary graduate program in the Biomedical Sciences at that Institution, before moving to San Antonio in 2004. Dr. Nicholson was named a Pew Scholar in the Biomedical Sciences in 1988, was awarded the Max Planck Prize with Klaus Willecke in 1993 and served as the President of the Association for Medical and Graduate Departments of Biochemistry from 2016-17. He was the first to sequence and identify the proteins that comprise gap junctions, going on to isolate and characterize many of the genes of this large family. His research program has focused on defining structural mechanisms behind their assembly, gating and regulation, and defining the permeability of their intercellular channels. More recently, he has investigated their roles in cancer, deafness and endometriosis. These mechanistic studies have led to a novel non-surgical diagnostic for endometriosis, and potentially the first curative therapy.
Title: The dawn of the molecular era of gap junction research and where it has led us 45 years later
Abstract: 68 year ago Furshpan and Potter¹ made the seminal discovery that neurons can couple electrically, as well as via chemical synapses. It then took 8 years to definitievly establish and name gap junctions as the structures that mediate this electrical coupling of cells². Another 15 years of toiling over various purification schemes, guided only by the morphology of the isolated material (gap junctions are one of the only detergent insoluble parts of the plasma membrane), led us to finally obtain the first partial sequence of a connexin³, the term adopted for gap junction proteins 8 years earlier by Goodenough⁴. Over the next 5 years, additional isolations and protein sequencing revealed that different tissues expressed distinct connexins⁵, and that some tissues (e.g. liver) express multiple members of the family⁶. Around this same time, the first 3 connexin genes (Cx32⁷, Cx43⁸and Cx26⁹) were isolated (cloned) using antibody screening of expression libraries or reverse translation of the protein sequence. With the advent of PCR, the pace of new gene discovery quickened, particularly thought the efforts of the Willecke lab.
This initiated the characterization of connexin channel diversity, initially focused on electrophysiology (gating, channel conductance, etc.), then increasingly on how the channels were regulated by physiological stimuli through kinases or cytoplasmically associated proteins and how connexin composition can dramatically affect channel permeability. After several years of lower resolution structural analyses, pioneered Yeager and Sosinsky, the first high resolution structure of a connexin channel was achieved through heroic efforts using traditional X-ray crystallography¹⁰. The advent of cryo-EM and more sophisticated molecular modeling soon expanded our understanding of channel structure and how it is regulated. Coincident with this, the field also began to appreciate the roles of connexins beyond intercellular communication, including adhesive functions and the roles of hemichannels on unopposed cell surfaces. The latter also expanded to embrace the contributions of pannexins, the unrelated descendants of invertebrate gap junction proteins (innexins). There is also now a growing recognition of the roles of connexin “fragments”, from internal translation products (GJA1-20K), to cytoplasmically cleaved C-tail domains or even full-length protein localized to organelles like mitochondria. What is clear is that after 50 years of molecular studies of connexins, new surprises into their diverse of functions still await.
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Furshpan EJ, Potter DD. J Physiol. 1959 145:289-325 (1959) PMID: 13642302
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Revel JP, Karnovsky MJ. J Cell Biol.33:C7–C12 (1967) PMID: 6036535
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Nicholson BJ, Takemoto LJ, Hunkapiller MW, Hood LE, Revel JP. Cell 32:967-978. (1983) PMID: 6299583
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Goodenough DA. Bulk J Cell Biol.61:557–563 (1974). PMID: 4363961
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Nicholson BJ, Gros DB, Kent SB, Hood LE, Revel JP. J Biol Chem 260:6514-6517. (1985) PMID: 2987225
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Nicholson BJ, Dermietzel R, Teplow D, Traub O, Willecke K and Revel JP. Nature 329:732-734 (1987) PMID: 2823143
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María Mayán
CellCOM group, CINBIO, University of Vigo
Dr. María Mayán is a senior researcher at CINBIO, Universidade de Vigo, Spain, where she leads a research group focused on the molecular mechanisms underlying aging-associated diseases and cancer. Her work has pioneered the study of connexin43 (Cx43) as a regulator of cellular senescence, tissue degeneration, and tumour plasticity, establishing new conceptual links between aging and cancer biology. Dr. Mayán has supervised several postdoctoral researchers, PhD candidates, and undergraduate students, and is actively involved in mentoring activities. Over the last decade, Mayán has made significant contributions to understanding the role of connexins and intercellular communication in osteoarthritis, age-related disorders, and cancer.
Dr. Mayán obtained her Bachelor's degree in Pharmacy from the University of Santiago de Compostela (Spain), her PhD in Biology from the Complutense University of Madrid at CIB-Margarita Salas (CSIC), and completed her postdoctoral training at the Faculty of Medicine, Imperial College London, and the Medical Research Council London Institute of Medical Sciences (MRC LMS), UK, before taking her first independent position at INIBIC in A Coruña (Spain). In 2023, she moved to CINBIO at the University of Vigo. Dr. Mayán has received several recognitions, including the Zendal International Award for Human Health and, more recently, the FERO Foundation Breast Cancer Research Grant.
Her research has identified novel functions of Cx43 in cellular senescence, DNA damage responses, and therapeutic resistance, opening new opportunities for the development of innovative therapeutic approaches. More recently, her group has developed extracellular vesicle-based platforms enriched in Cx43 for the targeted delivery of therapeutic mRNA to tumour cells. Dr. Mayán has authored numerous peer-reviewed publications in leading international journals, secured competitive national and international funding, and is an inventor on several patents. She actively coordinates and participates in multidisciplinary collaborations across Europe and regularly serves as an evaluator of grant proposals at the international level. Her group has secured strategic and innovation funding to develop therapeutic peptide-based approaches for the treatment of osteoarthritis by targeting specific activities of Cx43.
Title: Targeting Connexin43 in Aging and Cancer: A Context-Dependent Therapeutic Opportunity
Abstract: Connexin43 (Cx43) is the most widely expressed gap junction protein in human tissues and a key regulator of intercellular communication and signalling. Over the last decade, our work has identified Cx43 overactivity as a central mediator in the progression of age-related disorders. In age-related musculoskeletal diseases such as osteoarthritis, we demonstrated that aberrant regulation of Cx43 contributes to the acquisition of senescence-associated phenotypes, chronic inflammation, and tissue degeneration. Modulation of Cx43 signalling attenuates degenerative responses and restores tissue regeneration, supporting its role as a driver of age-associated disorders. In parallel, our studies in cancer have revealed more complex roles for Cx43. Cx43 upregulation enhances cellular senescence in different cancer subtypes, which can be exploited to improve therapy response. However, we have also identified a novel nuclear activity of Cx43, involving its interaction with nuclear lamins and the binding of DNA repair foci to the nuclear membrane, thereby restricting homologous recombination (HR). In a tumoral context characterized by high levels of DNA damage, or under targeted therapies that further enhance DNA damage, this activity leads to genomic instability and synthetic lethality, revealing a vulnerability that can be exploited to increase the efficacy of selected targeted therapies and halt resistance, one of the major challenges in cancer treatment. Besides, we have developed a platform of extracellular vesicles enriched in Cx43 for mRNA delivery to target tumour cells, opening new therapeutic strategies and opportunities. Altogether, our findings illustrate how the biological consequences of Cx43 activity are highly context-dependent, acting as a driver of tissue degeneration during aging while creating therapeutic vulnerabilities that can be exploited in cancer.
Jorge Enrique Contreras
Department of Physiology and Membrane Biology
School of Medicine, University of California Davis
Dr. Jorge Contreras is a Professor in the Department of Physiology and Membrane Biology at the University of California, Davis, where he leads a research program focused on understanding the molecular mechanisms regulating connexin and pannexin channels and their contributions to human disease. Dr. Contreras received his PhD at the Pontifical Catholic University of Chile and pursued postdoctoral training at the National Institutes of Health in the United States, developing an interdisciplinary research program at the interface of membrane biophysics, physiology, and cardiovascular biology. Dr. Contreras has pioneered studies on connexin hemichannels as critical regulators of cellular signaling, tissue function, and disease. By integrating structural biology, electrophysiology, imaging, and computational approaches, his work has established new principles in connexin biophysics and expanded the understanding of how these proteins function in health and disease. His laboratory recently revealed that connexin hemichannels operate as hybrid “chansporters,” demonstrating that ionic conduction and molecular permeation through these large-pore channels represent distinct and independently regulated functional properties. In addition, his laboratory has uncovered novel roles for connexin-43 hemichannels in pathological conditions, including cardiac stress responses, arrhythmogenesis, and cardiomyopathy. Dr. Contreras has authored numerous peer-reviewed publications and is actively involved in national and international scientific leadership. He currently serves as President of the Society of General Physiologists and previously served as Chair of the Channels, Receptors, and Transporters Subgroup of the Biophysical Society and President of the Latin American Society of Biophysics. Committed to training the next generation of scientists, Dr. Contreras has mentored undergraduate students, graduate students, postdoctoral researchers, and early-career investigators.
Title: Decoding Connexin Hemichannels: Structure, Function, and Regulatory Mechanisms
Abstract: Twenty years ago, the idea that connexin hemichannels functioned as active membrane channels in native tissues was met with considerable skepticism, and they were largely regarded only as precursors to gap junction channels. Today, hemichannels are increasingly recognized as dynamic regulators of cellular signaling and intercellular communication. Nevertheless, our understanding of the structural and biophysical mechanisms governing hemichannel function remains incomplete. In this keynote presentation, I will discuss recent advances in connexin hemichannel gating, permeation, and regulation, with emphasis on the molecular mechanisms and conformational changes that control channel activity. I will highlight emerging concepts that are reshaping our understanding of hemichannel biology and defining new directions for the field.
Brant E. Isakson
Robert M. Berne Cardiovascular Research Center
Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, Virginia USA
Brant obtained his Bachelor’s degree in History, but wasn’t smart enough to make a career of it. For that reason he obtained his PhD in Zoology and Physiology in 2003 hoping to study bear hibernation. That didn’t work either, so Brant began a post-doc with Brian Duling at the University of Virginia and focused on heterocellular communication between endothelium and smooth muscle in the microcirculation. In 2007 Brant began his own lab at the University of Virginia as a Resident Faculty Member in the Robert M. Berne Cardiovascular Research Center and an Assistant Professor in the Department of Molecular Physiology and Biophysics. In 2017 Brant was given an endowed title of Pinn Scholar, and in 2018 promoted to Professor. He is PI of the longest-running (45+ years) Basic Cardiovascular T32 at UVA. Brant has over 170 publications (including a book on dinosaur physiology) with multiple patents and licensed antibodies, is currently President of the Microcirculatory Society, and incoming Editor-in-Chief of AJP-Heart. He has been continuously funded by the NIH since 2007, and sits on multiple study sections and editorial boards. He is especially proud of his trainees and their amazing accomplishments; all his pre- and post-docs received their own extramural funding, with many receiving AHA CDAs and K99/R00s, and a plethora are now in faculty positions of their own.
In terms of the IGJC, Brant began his work in the gap junction field as a graduate student trying to understand Ca2+ and IP3 movement between cells with connexin mimetic peptides, and this was also the initial basis of his post-doc. At the start of his faculty career, the work shifted from gap junctions to trying to examine connexin hemichannels…but all those projects failed. He then turned his attention to the easier to understand pannexin channel. From there his lab created the first floxed Panx1 mouse, described the first non-apoptotic role for pannexins in physiology (focused on the vasculature), unbiased screens for pannexin inhibitors, pannexin inhibitory peptides, and the first pannexin phospho-dead mutant mice. He shares these reagents widely and loves the creative process of collaboration on these fascinating channels.
Title: Pannexins Need a Friend
Abstract: Pannexins are often introduced as large-pore channels, but that shorthand misses their more interesting habit: they almost never work alone. This keynote will argue that Panx1, and our emerging understanding of Panx3, are best viewed as context-dependent signaling partners rather than isolated conduits. As our work in the vasculature has demonstrated, Panx1 rarely initiates biology de novo. Instead, it is recruited downstream of receptors, injury cues, inflammatory mediators, and post-translational modifications to amplify local signals into tissue-level responses. For example, Panx1 participates in α1-adrenergic receptor–dependent vasoconstriction, leukocyte emigration through venous endothelium, TNFα-induced endothelial permeability, ischemic stroke severity, myocardial infarction responses, and ischemia–reperfusion injury. Across these examples, the “message” is not simply Panx1 opening; it is Panx1 opening in the right cell, at the right membrane domain, in conversation with purinergic receptors, calcium signaling, caveolae, inflammatory programs, and ATP/metabolite release that feeds back on neighboring cells. This work will broaden that model beyond Panx1 to Panx3, where we show that this isoform also needs a friend. In this case, Golgi-localized Panx3 stabilizes the transcriptional repressor Bcl6 in endothelial cells, thereby restraining Nox4-driven hydrogen peroxide production. Together, these findings support a reframing of pannexins as molecular amplifiers, scaffolds, and coincidence detectors. Their importance lies less in acting alone than in determining which cellular conversations become loud enough to matter in inflammation, vascular tone, and cardiovascular disease. By treating each pannexin as a participant in a signaling ensemble, rather than as a solitary pore, we gain clearer hypotheses for mechanism and therapy.
Nathalie Rouach
Collège de France
Nathalie Rouach is a neurobiologist developing research on the role of glial cells in brain physiology and pathologies. She is an Inserm Research Director at Collège de France, Paris. She received her Ph.D. in Neuroscience, performed jointly at University Pierre and Marie Curie and the Weizmann Institute, where she studied the contribution of astrocytic gap junctional communication to neuroglial network interactions. She then joined the laboratory of Roger Nicoll at University of California San Francisco as a postdoc, where she worked on glutamate receptors trafficking and synaptic plasticity. She now runs the laboratory « Neuroglial Interactions in Cerebral Physiopathology and Pathologies » within the Interdisciplinary Center for Research in Biology at the Collège de France. Her research aims at determining whether and how astrocytes play a direct role in information processing. In particular, her team explores the molecular modalities and functional consequences of neuron-glia interactions in various physiological and pathological contexts, such as memory, social interactions, epilepsy or intellectual disability, with ex vivo and in vivo studies of neuronal excitability, synaptic transmission and plasticity, synchronization of neuronal networks, and cognitive functions in mouse models or human tissues. N. Rouach is a French Government Oversea Fellow of Churchill College (Cambridge, UK), is an elected member of the Academia Europeae section “Physiology & Neuroscience” and has received several awards including the Human Frontier Career Development award (2006), the Emergence award and Silver Medal of the City of Paris (2012), the Rachel Ajzen and Leon Iagolnitzer prize (2022), the Grand Prize by the Sicard Foundation-French Academy of Sciences (2024) and is a Laureate of ERC Consolidator (2016) and Proof of Concept (2022) grants as well as of a Chair of excellence in Biology-Health (ANR, French National Research Agency) (2025).
Title: The many ways astroglial connexins and pannexins regulate neurotransmission and behavior
Abstract: Our laboratory investigates how astrocytes regulate brain information processing. We particularly explore the molecular modalities and functional outcomes of astrocyte-neuron interactions in various physiological and pathological contexts, such as memory, vision, social interactions, epilepsy or intellectual disability, focusing ex vivo or in vivo on neuronal excitability, synaptic transmission, plasticity, synchronization and cognitive functions. To do so, we use a multidisciplinary approach combining electrophysiology, imaging, behavioral testing, mathematical modeling and molecular tools targeting selectively astrocytes in situ and in vivo in mice and human tissues.
In this talk, I will present some of the fundamental research we performed in the last years on the role of astroglial connexins and pannexins in synaptic transmission, plasticity, network activity and behavior in normal and pathological conditions. In particular, I will present some of the many ways these proteins control neuronal wiring and activity via regulation of the extracellular matrix, ion homeostasis, gliotransmitter release or astroglial synapse coverage, and show how our work fuels the emerging concept of neuroglial networks, in which astrocytes actively participate to the formation, activity and plasticity of neuronal networks underlying behavior.
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Physiological synaptic activity and recognition memory require astroglial glutamine. G. Cheung, D. Bataveljic, J. Visser, N. Kumar, J. Moulard, G. Dallérac, D. Mozheiko, A. Rollenhagen, P. Ezan, C. Mongin, O. Chever, A.P. Bemelmans, J. Lübke, I. Leray, N. Rouach. Nature Communications. 2022. 13(1):753.
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Astrocytes close the mouse critical period for visual plasticity. J. Ribot, R. Breton, C.F. Calvo, J. Moulard, P. Ezan, J. Zapata, K. Samama, M. Moreau, A.P. Bemelmans, V. Sabatet, F. Dingli, D. Loew, C. Milleret, P. Billuart, G. Dallérac, N. Rouach. Science. 2021. 373(6550):77-81
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Pannexin1 channels contribute to seizure generation in human epileptic brain tissue and in a mouse model of epilepsy. E. Dossi, T. Blauwblomme T, J. Moulard, O. Chever, F. Vasile, E. Guinard, M. Le Bert, I. Couillin, J. Pallud, L. Capelle, G. Huberfeld, N. Rouach. Science Translational Medicine. 2018. 10(443). pii: eaar3796.
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Connexin 30 sets synaptic strength by controlling astroglial synapse invasion. U. Pannasch, D. Freche, G. Dallérac, G. Ghézali, C. Escartin, P. Ezan, M. Cohen-Salmon, K. Benchenane, V. Abudara, A. Dufour, J.H.R. Lubke, N. Déglon, G. Knott, D. Holcman, N. Rouach. Nature Neuroscience. 2014. 17:549-558.
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Astroglial metabolic networks sustain hippocampal synaptic transmission. N. Rouach, A. Koulakoff, P. Ezan, K. Willecke, C. Giaume. Science. 2008. 322:1551-5.