Joana Neves Lab

Ageing & Tissue Repair – Immune Modulation in Tissue Repair

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 ageing. 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.

In the Neves Lab we use 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 ageing 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.

The Neves Lab is part of the Ageing & Tissue Repair joint lab, running two independent, complementary and cooperative research programs led by two group leaders: The research program in Sousa-Victor Lab aims to understand intrinsic limitations of aged stem cells. The Neves Lab is focused on inflammatory signaling in ageing and immune modulatory strategies to improve regenerative success. Our goal is to apply the insights from the study of alterations in the ageing immune environment and stem cell ageing 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 Ageing & 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.

Research Team

Research Areas

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

Ongoing Research Projects

2020/2021 MANF Role in Bone Marrow Hematopoiesis. Coordinator: Pedro Sousa-Victor and Joana Neves. Funding Agency: Genentech, Inc.

Awards

2017 Prize for best oral presentation at European Retina Meeting

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

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

2010 Postdoctoral Fellowship, by Science and Technology Foundation (FCT, Portugal)

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

2006 PhD Fellowship, by Science and Technology Foundation (FCT, Portugal)

Selected Publications

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.

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

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.

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.

*equal contribution

**Corresponding author