Dr. Ambrosi's academic training and research experience have provided him with a broad background for the interrogation of developmental, pathological, and aging-related processes of the musculoskeletal system. He holds a German engineering diploma (Dipl.Ing., equals combined BS & MS) from TU Berlin and a master’s degree in Bioengineering from Dongseo University, South Korea. During his undergraduate studies at the Julius-Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charité Berlin, he examined the effect of mechanical stimuli on lineage decisions of bone-resident stem cells. The work in Dr. Kay Raum’s lab set the stage for his graduate research at the German Institute of Human Nutrition in the newly established lab of Dr. Tim J. Schulz, earning him a Ph.D. from the University of Potsdam, Germany, by delineating the developmental origin and function of bone marrow adipose tissue, becoming one of the pioneers in this research area. Initially supported by a two-year postdoctoral scholarship from the German Research Foundation, he conducted his postdoctoral training in the lab of Dr. Charles Chan at Stanford University, where he later received a prestigious NIA/NIH K99/R00 Award to study skeletal stem cell biology with focus on aging.

Skeletal stem cells are in the front and center of our research endeavors. Research spans the continuum of basic to translational research.  We use a combination of mouse models and human tissues to study the biology of SSCs in health and disease. Our research encompasses a wide range of leading-edge techniques, from flow cytometry to single cell omics and in vivo cellular barcoding to spatial transcriptomics, to gain a comprehensive understanding of the cellular and molecular mechanisms that govern SSC behavior.

Skeletal Stem Cell Diversity and Lineage Dynamics

This research direction focuses on understanding the diversity, lineage dynamics, and differentiation trajectories of skeletal stem cells (SSCs) in both mice and humans. We aim to gain a comprehensive understanding of the cellular and molecular mechanisms that drive SSC behavior in health and disease. To achieve this goal, we employ a wide range of cutting-edge techniques, including single cell sequencing, flow cytometry, transplantation assays, and in vivo clonal tracking, to study the diversity and lineage dynamics of SSC populations. Our cellular barcoding techniques allow us to track the behavior of individual cells and their descendants over time, gain functional insights one cell at a time with multiparameter readouts, thereby providing a detailed view of SSC behavior during distinct perturbations. We are also exploring spatial transcriptomics techniques to get a more comprehensive understanding of the exact cellular and molecular architecture of SSC lineage populations. Our long-term goal is to use this knowledge to develop new therapies and interventions that can prevent and reverse SSC-based aging and malignancies in both the skeletal and hematopoietic systems.

Mechanisms of Skeletal Stem Cell Dysfunction during Aging and Disease

Another big focus in our lab pertains to the understanding of the mechanistic underpinnings that drive an intrinsically aged state in SSCs, that we have shown to be detrimental to skeletal and hematopoietic health. SSCs reside in specialized microenvironments in the bone marrow, known as niches, which provide the necessary signaling cues that regulate the behavior of SSCs and the hematopoietic stem cells (HSCs) that reside alongside them. The composition of SSC niches, cellular architecture, and molecular crosstalk are essential for maintaining the balance between the formation of bone and blood cells. However, with aging and disease, these niches change. Our goal is to map changes in SSC niches during aging as well as to extend our efforts to gain new insight into the development of metastatic bone marrow niches and osteosarcomas.

Endocrine Interactions of the Skeletal Stem Cell System

Endocrine interactions play an important role in the regulation of SSCs and bone health. The function of SSCs is influenced by a variety of circulating factors. For example, glucocorticoids (GCs), a class of steroid hormones that are involved in the regulation of various physiological processes, including the immune response and metabolism, have a great impact on skeletal biology. Excessive or prolonged exposure to GCs can lead to bone loss, a condition known as glucocorticoid-induced osteoporosis (GIOP). We are trying to understand how SSC lineage dynamics and crosstalk to other bone-resident cell types are altered during chronic exposure to GCs. Additionally, we are studying the bone-brain axis, which refers to the connection between the skeleton and the central nervous system that is critical for the regulation of bone metabolism. The central regulation of bone is mediated by hormones and neurotransmitters, which interact with SSCs to modulate their behavior and function. Together with our collaborators from the field of neuroscience we are elucidating new sex-specific factors released from the brain that drive high bone mass. This line of research could potentially reveal new anti-osteoporosis drug.

• ASBMR John Haddad Young Investigator Award, 2022
• Young Investigator Award of the ASBMR, 2021
• Young Investigator Travel & Merit Award of the ISSCR, 2021
• ASBMR pre-meeting Best Scientific Oral Presentation Award, 2020
• Travel & Best Oral Presentation Award of the Bone Marrow Adiposity Society, 2019
• Young Investigator Travel & Merit Award of the ISSCR, 2019                                     
• German Research Foundation (DFG) Postdoc Abroad Scholarship (2-year), 2018                                       
• Ph.D. Thesis Award, Berlin School of Regenerative Medicine (BSRT), Charité Berlin, 2017
• Michelson-Award, University of Potsdam Best Dissertation 2016/17 Award, 2017
• German Academic Exchange Service (DAAD) Full Scholarship to Study Abroad, 2010

• The American Society for Bone and Mineral Research (ASBMR)
• International Society for Stem Cell Research (ISSCR)
• BoneMarrow Adiposity Society (BMAS)

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