From the US to TIGEM: Marco Angelozzi’s Journey in Skeletal Biology

TIGEM has long been at the forefront of research on lysosomal storage disorders (LSDs), many of which—including mucopolysaccharidoses (MPS)—are characterized by severe skeletal abnormalities that remain challenging to treat. As part of our growing commitment to unraveling the pathophysiology of these complex diseases and developing innovative therapeutic strategies, we are thrilled to welcome Dr. Marco Angelozzi as a new Staff Scientist in Carmine Settembre’s laboratory. Trained in skeletal biology, Marco brings deep expertise in the molecular and cellular mechanisms regulating bone and cartilage development. After earning his PhD in Biomedical Sciences and Biotechnology from the University of Ferrara, he refined his specialization in the United States under the mentorship of Dr. Véronique Lefebvre at the Children’s Hospital of Philadelphia (CHOP), a world leader in skeletal and neurodevelopmental disease research. In Dr. Lefebvre’s lab, Marco investigated how SOX transcription factors control the differentiation and function of skeletal progenitor cells and chondrocytes, and how their dysfunction contributes to rare congenital malformations.

At TIGEM, Marco joins the laboratory of Dr. Carmine Settembre, which investigates how lysosomal dysfunction, particularly defects in autophagy, affects extracellular matrix formation and bone development. The lab has shown that autophagy acts as a quality control system for collagen, and its disruption contributes to skeletal abnormalities seen in LSDs. Supported by multiple ERC grants, the group is exploring how cargo is selectively targeted in autophagy to uncover new therapeutic strategies for genetic and age-related diseases. Marco’s expertise in skeletal biology adds a valuable dimension to these efforts, strengthening TIGEM’s mission to understand and treat bone-related manifestations of rare disorders.

In this interview, Marco reflects on his career path, what led him to return to Italy, and his ambitions for future research at TIGEM.

Could you briefly introduce yourself?  

Hi! My name is Marco Angelozzi. I'm from Ascoli Piceno and I am a skeletal biologist curious about the mechanisms driving bone development and disease. I obtained my PhD in Biomedical Sciences and Biotechnology at the University of Ferrara in the lab of Prof. Roberta Piva where I focused on the realization of 3D in vitro systems of bone and cartilage formation. At the end of 2017, I moved to the US to carry out a post-doc in Dr. Véronique Lefebvre lab at the Children's Hospital of Philadelphia. I learned to work with transgenic mouse models to study bone development and genetic diseases of the skeleton with a focus on SOX transcription factors. After my post-doc, I decided to stay in Philly as a scientist for a few more years, until last April when I joined TIGEM.

After so many years in the United States, what motivated you to return to Italy and choose TIGEM for this new phase of your career?

I had for a while the thought of coming back to Italy for both work and personal reasons, but the opportunity to join TIGEM was a crucial factor in my decision. I think this is an amazing place for doing great science—not only because of the stimulating scientific environment, but also because of TIGEM’s strong reputation in the field of rare genetic diseases. The institute is widely recognized for its ability to bridge basic research and mechanistic studies in cell biology with translational applications aimed at understanding and treating human diseases. TIGEM also has a solid track record in the study of bone-related disorders, which aligns perfectly with my background and interests. This environment will allow me to explore new ideas and research directions, with the goal of making my work increasingly translational and impactful for patients—and, hopefully, for my own scientific growth as well.

How would you describe your area of expertise, and how do you think it could open new paths in TIGEM's research?

I describe myself as a skeletal molecular biologist. Most of my work has been dedicated to understanding how the SOX transcription factors are involved in the embryonic and postnatal development of the skeleton and how the dysregulation of these genes causes both pediatric and adult bone diseases. Most recently, my focus has shifted on trying to develop gene therapy for achondroplasia, the most common form of short stature in humans. Over the years, I matured a strong expertise in applying molecular techniques to the study of cartilage and bone. This is not always easy since these tissues are highly complex, continuously evolving, rich in dense extracellular matrix, and are present in our body in different sizes and shapes. I believe that my expertise will greatly fit in at TIGEM and I hope it will bring opportunities for new projects and collaborations regarding the development of therapies for genetic diseases where the skeleton is affected.

Is there anything from the American academic or scientific system that you would like to bring — or are already bringing — into your work here in Italy?

One thing I really enjoyed as a scientist in the US was the possibility to access any kind of resource and cutting-edge technique. I consider both these points important in building a strong scientific community. That said, I believe that TIGEM already offers a comparable environment, with excellent infrastructure and technologies that support ambitious research. In particular, the institute’s in-house facilities—such as advanced microscopy platforms, animal models, and dedicated technological resources—provide the ideal infrastructure to conduct high-level, cutting-edge research. This model of integrating core facilities directly within a research institute is a hallmark of top international centers, and TIGEM was forward-thinking in adopting it early on. It fosters collaboration, accelerates discovery, and enhances scientific output.

I also appreciated the mentoring culture at CHOP, which encouraged connections between trainees and senior investigators; I find TIGEM’s commitment to mentoring equally impressive. The presence of three PhD programs on site contributes to a dynamic and intellectually rich environment, where junior and senior scientists interact daily. This culture of exchange and support creates the perfect ground for training the next generation of researchers and for developing impactful, collaborative science.

How do you envision the long-term impact of your work here? What challenges or opportunities do you foresee in the near future?

One of the main challenges I set myself is to develop gene therapies for skeletal diseases. To this day, gene therapies have not been successful when applied to the skeleton mainly due to the lack of vectors that could efficiently target cartilage and bone. My work at TIGEM will be dedicated to filling this gap. Specifically, I will focus on developing new delivery strategies that will help correct bone defects in patients affected by mucopolysaccharidoses. I hope that the results obtained by these studies will open new paths for the treatment of other skeletal dysplasias. I believe that TIGEM will be the perfect place to see this project realized. I look forward to becoming an integral part of the research community here and, maybe one day, lead my own research group.