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).