Romeo Blanc

Position title: Assistant Professor

Phone: 608-262-3775

Address:
RESEARCH INTERESTS - Aging, Epigenetics, Stem Cell Biology, Inflammation, Muscle regeneration

Address: 4553 WIMR II – 1111 Highland Ave. – Madison, WI 53705

Research Goals

In our lab, we are dedicated to uncovering the intricate mechanisms of stem cell aging, with a particular focus on the inflammatory-driven epigenetic regulation of stem cells. As we age, the intrinsic ability of stem cells to self-renew and differentiate to maintain tissue integrity dramatically declines. Understanding the processes leading to stem cell dysfunction with age is essential for developing novel, effective stem cell-based therapies to treat disorders associated with aging.

Muscle stem cell differentiation on cultured single muscle fibers. Quiescent MuSCs are Pax7+MyoD- (Green), while committed progenitors are Pax7-MyoD+ (Red).

The Blanc lab uses two models to study stem cell aging: muscle stem cells (MuSCs) and hematopoietic stem cells (HSCs). We are also very interested in the complex relationship between their respective niches, skeletal muscle and bone marrow. In mammals, MuSCs are required to ensure life-long skeletal muscle regeneration, while HSCs give rise to blood cells. HSC-derived immune cells are critical to ensure the temporal regulation of muscle regeneration through several processes ranging from debris clearance to guiding proper MuSC differentiation. Both stem cell populations share similar aging features such as quiescence disruption and aberrant fate regulation, including premature cell death and impaired lineage commitment.

Our research aims to elucidate the epigenetic mechanisms of stem cell aging, manipulate them to rejuvenate aged tissue, and promote healthy aging. We have divided our research into several key projects to address these complex questions.

Project 1: Aerobic Exercise and Systemic Rejuvenation

This project focuses on the systemic effects of moderate aerobic exercise on stem cell function and tissue rejuvenation.

In the elderly, tissue regeneration is often compromised, and repeated injuries can diminish the health benefits of exercise. While mild voluntary exercise is a powerful way to rejuvenate several stem cell niches in aged mice, the exact mechanisms underlying this rejuvenation process remain undetermined. Additionally, while exercise has tremendous benefits, it is not always a realistic method for patients with disabilities or muscle weakness. In this ambitious project, our lab explores how exercise-induced stimulation of H4K20me1 can rejuvenate the function of muscle and hematopoietic stem cells in aged mice. We aim to use our discoveries to manipulate identified pathways and recapitulate the benefits of exercise.

Project 2: Epigenetic Mechanisms of Stem Cell Aging

This project explores the molecular and epigenetic mechanisms underlying stem cell aging, with a particular emphasis on the link between iron metabolism, ferroptosis, and inflammation.

Aging is associated with a decline in stem cell functionality and number across the organism. In this project, we aim to further unravel Muscle Stem Cells (MuSCs) aging by assessing how systemic factors influence MuSC fate decisions through long-term epigenetic landscape remodeling. As aging is intricately linked to a pro-inflammatory shift, we recently studied the epigenetic effects of inflammatory signals in MuSCs and found decreased H4K20me1 levels. This epigenetic erosion disrupts MuSC quiescence, largely through the epigenetic silencing of Notch target genes. In the setting of inflammatory signals or aging, the lack of Kmt5a and the subsequent absence of de novo H4K20me1 culminate in cell death by a newly identified form of regulated cell death: ferroptosis.

Our lab recently showed that ferroptosis is the predominant mode of cell death in aged MuSCs; a phenomenon we also observed in aged hematopoietic stem cells (HSCs). Implementing preventative strategies to inhibit systemic inflammation prevented aged MuSC ferroptosis, preserving their numbers and regenerative capabilities. This intervention significantly enhanced aged muscle regeneration and strength recovery, extending both lifespan and healthspan in mice

By addressing these research questions, our lab aims to uncover novel therapeutic targets and strategies to rejuvenate aged stem cells, enhance tissue regeneration, and promote healthy aging.

Notable Publications:

Blanc, R. S. et al. Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis. Pre-Print (2024). https://doi.org:10.21203/rs.3.rs-3937628/v1

Blanc, R. S. et al. Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury. Nat Commun 11, 4167 (2020). https://doi.org:10.1038/s41467-020-17620-8

Blanc, R. S. & Richard, S. Arginine Methylation: The Coming of Age. Mol Cell 65, 8-24 (2017). https://doi.org:10.1016/j.molcel.2016.11.003