Neves & Sousa-Victor Lab

Ageing & Tissue Repair

The Aging & Tissue Repair joint lab includes two independent, complementary and cooperative research programs led by two group leaders: Joana Neves is focused on inflammatory signaling in aging and immune modulatory strategies to improve regenerative success. Pedro Sousa-Victor aims to understand intrinsic limitations of aged stem cells. The goal is to apply the insights from the study of alterations in the aging immune environment and stem cell aging to develop new stem cell-based therapies to improve the health of old individuals. By studying stem cell function and immune modulatory mechanisms in an integrated manner, rather than as independent problems in the biology of tissue repair, we aim to provide a better understanding of the problems and optimized strategies for stem-cell based therapies in aging.

The Aging & Tissue Repair joint lab uses Drosophila and in vitro models as platforms for screening, discovery and mechanistic studies, which are then translated into functional studies using mouse models and validated in human samples.

Aging is characterized by a decline in the organism’s physiological integrity and vulnerability to disease. Although the consequences of aging on human health are broadly apparent, the causes and drivers of the aging process are just beginning to be understood. An important hallmark of aging is the loss of regenerative capacity that results from age-related changes in the systemic environment and the niche, as well as intrinsic limitations of stem cells themselves.

A central goal of regenerative medicine is the ability to restore or rejuvenate tissues using stem cells. This approach relies on harnessing repair processes that have evolved to heal damaged tissues and to maintain tissue homeostasis. Immune modulation is an integral part of the process of tissue repair, and dysregulated immune responses are likely contributors to tissue dysfunction observed in old individuals. Age-associated inflammation, in particular, is likely an important roadblock for the success of regenerative therapies in aging. Thus, immune modulation aimed towards harnessing the anti-inflammatory function of immune cells to promote endogenous repair mechanisms is a promising strategy to improve regenerative success in older individuals. Ultimately, the success of regenerative therapies in age-related diseases depends on combined strategies targeted at overcoming these interacting roadblocks to tissue repair in aging.

Immune Modulation in Tissue Repair

Joana Neves’ team uses skeletal muscle regeneration as a paradigm of tissue repair to understand the molecular and cellular basis of the immune modulatory component of tissue regeneration and how its dysregulation in aging and disease can be targeted to optimize regenerative success. Our goal is to identify pathways that are used by immune cells to modulate the inflammatory tone of the tissue environment, with the goal of identifying new molecules with immune modulatory properties and therapeutic potential in regenerative medicine applied to old patients.

Stem Cell Aging

Pedro Sousa-Victor and his team use muscle aging as a model system to understand mechanisms of stem cell aging. We are currently working on three main research lines that aim to integrate knowledge of intrinsic mechanisms that drive stem cell loss of function with age (i) with immune-derived signaling in muscle regenerative responses (ii) to devise combinatorial approaches for improving the success stem-cell based therapies applied to the sarcopenic muscle (iii).

Research Team

Research Areas

Immune Modulation in Tissue Repair

• Mechanisms of immune modulation in regeneration and stem-cell therapies
• MANF biology: molecular and cellular mechanisms of action
• Immune signaling in aging

Stem Cell Aging

• Mechanisms of intrinsic stem cell aging
• Modulation of stem cell function by immune derived factors
• Stem cell-based therapies in sarcopenia

Ongoing Research Projects

2022/2023 Regulação imune da reparação de tecidos durante o envelhecimento. Coordinator: Joana Neves. Funding Agency: Fundação para a Ciência e a Tecnologia.

2021/2023 Rejuvenating Strategies for Stem Cell-Based Therapies in the Aged Skeletal Muscle. Coordinator: Pedro Sousa-Victor. Funding Agency: Fundação para a Ciência e a Tecnologia.

2020/2024 EMBO Young Investigator Network. Coordinator: Pedro Sousa-Víctor. Funding Agency: European Molecular Biology Organization.

Awards

2019 | Joana Neves | Sartorius & Science Prize for Regenerative Medicine & Cell Therapy.

2019 | Pedro Sousa-Victor | Junior Leader Fellowship by “la Caixa” Foundation.

2018| Pedro Sousa-Victor | Prize of Best Scientific work to “MANF is an evolutionary conserved anti-gernonic factor” at Bay Area Aging meeting, UC Berkley.

2017 | Joana Neves | Prize for best oral presentation at European Retina Meeting.

2016-2019 | Pedro Sousa-Victor | Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research.

2016-2017 | Joana Neves | Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research.

2015 | Pedro Sousa-Victor | La Vanguardia of Science Award to “Geriatric muscle stem cells switch reversible quiescence into senescence”.

2015 | Pedro Sousa-Victor | City of Barcelona award to “Geriatric muscle stem cells switch reversible quiescence into senescence”.

2013-2014 | Joana Neves | Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research.

2010 | Joana Neves | Postdoctoral Fellowship, by Science and Technology Foundation (Fundação para a Ciência e a Tecnologia, Portugal).

2007 | Joana Neves | Prize for best oral presentation at Developmental Biology Retreat, by the Catalan Society of Developmental Biology.

2006 | Joana Neves | PhD Fellowship, by Science and Technology Foundation (Fundação para a Ciência e a Tecnologia, Portugal).

2006 | Pedro Sousa-Victor | PhD Fellowship by Science and Technology Foundation (Fundação para a Ciência e a Tecnologia, Portugal).

Selected Publications

Sousa NS, Brás MF, Antunes IB, Lindholm P, Neves J**, Sousa-Victor, P**(2023). Aging disrupts MANF-mediated immune modulation during skeletal muscle regeneration. Nature Aging. https://doi.org/10.1038/s43587-023-00382-5

Munoz-Canoves P**, Neves J, Sousa-Victor P** (2020). Understanding muscle regenerative decline with aging: new approaches to bring back youthfulness to aged stem cells. FEBS Journal 287(3):406416. Review.

Neves J**, Sousa-Victor P** (2020). Regulation of inflammation as an anti-aging intervention. FEBS Journal 287(2020):43–52. Perspective.

Joana Neves, Pedro Sousa‐Victor (2019) Regulation of inflammation as an anti‐aging intervention. FEBS Journal Sep 16. doi: 10.1111/febs.15061. [Epub ahead of print].

Sousa-Victor P*, Neves, J*, Cedron-Craft, W, Ventura, PB, Liao, CY, Riley, RR, Soife, I, van Bruggen, N, Kolumam, GA, Villeda, SA, Lamba DA, Jasper H (2019) MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage. Nature Metabolism 1: 276–290.

Sousa-Victor P**, Jasper H, Neves J** (2018) Trophic Factors in Inflammation and Regeneration: The Role of MANF and CDNF. Frontiers in Physiology 9:1629.

Sousa-Victor P, Garcia-Prat L, Munoz-Canoves P (2018) New mechanisms driving muscle stem cell regenerative decline with aging. The International Journal of Developmental Biology 62: 583-590.

Neves J*, Sousa-Victor P*, Jasper H (2017) Rejuvenating Strategies for Stem Cell-Based Therapies in Aging. Cell Stem Cell 20:161-175.

Sousa-Victor P, Ayyaz A, Hayashi R, Qi Y, Madden DT, Lunyak VV, Jasper H (2017) Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells. Cell Reports 20: 2527-2537.

Garcia-Prat L*, Sousa-Victor P*, Munoz-Canoves P (2017) Proteostatic and Metabolic Control of Stemness. Cell Stem Cell 20: 593-608.

Neves J, Zhu J, Sousa-Victor P, Konjikusic M, Riley R, Chew S, Qi Y, Jasper H, Lamba DA (2016) Immune modulation by MANF promotes tissue repair and regenerative success in the retina. Science 353: aaf3646.

Neves J*, Demaria M*, Campisi J, Jasper H (2015) Of Flies, Mice, and Men: Evolutionarily Conserved Tissue Damage Responses and Aging. Developmental Cell 32(1):9-18.

Sousa-Victor P, Garcia-Prat L, Serrano AL, Perdiguero E, Munoz-Canoves P (2015) Muscle stem cell aging: regulation and rejuvenation. Trends in Endocrinology and Metabolism: TEM 26: 287-296.

Sousa-Victor P, Gutarra S, Garcia-Prat L, Rodriguez-Ubreva J, Ortet L, Ruiz-Bonilla V, Jardi M, Ballestar E, Gonzalez S, Serrano AL, Perdiguero E, Munoz-Canoves P (2014) Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506: 316-321.

Petrovic J*, Formosa P*, Luna JC, Ibañes M**, Neves J**, Giraldez F** (2014) Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear. Development 141(11):2313-24.

Neves J*, Parada C*, Chamizo M, Giraldez F (2011) Jagged 1 regulates the restriction of Sox2 expression in the developing chicken inner ear: a mechanism for sensory organ specification. Development 138(4):735-44.

Perdiguero E,Sousa-Victor P, Ruiz-Bonilla V, Jardi M, Caelles C, Serrano AL, Munoz-Canoves P (2011) p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair. The Journal of Cell Biology 195: 307-322.

*equal contribution

**Corresponding author