Throughout his professional career, Alessandro Vindigni, PhD, has always been fascinated by the mechanisms that bridge DNA and people together. An expert in genome integrity, Vindigni’s diverse background spans extensive research in DNA repair to years of experience collaborating and strengthening interactions with the international scientific community. Today, Vindigni, Professor, Washington University School of Medicine, Department of Medicine – Oncology Division and Pathology and Immunology, is researching DNA replication and repair, and the roles of these pathways on cancer initiation, progression, and response to chemotherapy and immunotherapy. He is also sharing his talents collaboratively with member investigators as part of the new Center for Genome Integrity.
Building a Career in Genome Integrity
Born in Italy, Vindigni completed his graduate training in biochemistry and molecular biophysics at the University of Padova, followed by postdoctoral training at Washington University School of Medicine. He went on to serve as Group Leader in Genome Stability at the International Centre for Genetic Engineering and Biotechnology (ICGEB) , an intergovernmental organization aligned with the United Nations Common System. For over 10 years, Vindigni worked with ICGEB by advancing research, training, and technology transfer in countries around the globe. Vindigni eventually relocated to St. Louis in 2011 for a faculty appointment at Saint Louis University, and in 2019, he accepted his current position at Washington University School of Medicine.
His lab is investigating the pathways by which actively replicating cancer cells respond to chemotherapeutics and is searching for insights on how to target these pathways to increase chemotherapeutic sensitivity. To achieve these goals, Vindigni’s team uses a unique combination of biochemical, cellular, and electron microscopy approaches that allow direct visualization of the structure of DNA replication forks at single-molecule resolution.
By understanding how these DNA replication stress response pathways work, we can then develop strategies to stop their ability to overcome DNA lesions, thereby making cancer cells much more sensitive to DNA-damaging chemotherapeutics.
Alessandro Vindigni, PhD
DNA replicates by unzipping its two interwoven strands and making copies of each. As the DNA strands separate and copy, they form a “replication fork”. To stop cancer cells, which proliferate by replicating faster than healthy cells, many chemotherapy drugs work by inducing DNA lesions with the hope of introducing an “obstacle” that blocks DNA replication. However, cancer cells have evolved strategies to overcome these replication “obstacles”, allowing them to proliferate despite the chemotherapy “obstacle”. Vindigni’s goal is to define the DNA replication stress response pathways that allow replication forks to overcome DNA lesions to halt this escalation. In previous research, Vindigni’s team identified several enzymes involved in these pathways and provided important clues on how to target these enzymes to increase chemotherapy response. “By understanding how these DNA replication stress response pathways work,” explains Vindigni, “we can then develop strategies to stop their ability to overcome DNA lesions, thereby making cancer cells much more sensitive to DNA-damaging chemotherapeutics.”
Several studies of Vindigni’s recent work on this topic can be found here on the Vindigni Lab website.
Center for Genome Integrity
Upon his arrival at WashU, Vindigni was interested in creating a community within the School of Medicine focused on DNA repair. With support from the Division of Oncology and Siteman Cancer Center, in April 2021 the Center for Genome Integrity (CGI) was launched as a multi-disciplinary scientific community dedicated to defining mechanisms of genome instability that impact human health.
Vindigni is director of the Center’s Core Leadership Council, a group of five faculty all researching different areas related to genome integrity. The Center also includes member investigators from departments across Washington University School of Medicine and Saint Louis University.
“We hope that by fostering interactions between clinical and basic science researchers,” explains Vindigni, “we can help promote more multi-investigator grants and encourage the translation of basic science advances into the clinic.”
As part of their educational efforts, the Center offers a seminar series investigating current topics ranging from the basic biology of DNA replication and repair to our current understanding of how defects in these pathways drive cancer initiation, progression, and response to chemotherapy and immunotherapy. Currently, the Genome Maintenance and Cancer or GMaC virtual seminar series is offered through spring 2022 and features distinguished clinician and basic scientist speakers from around the world. Details about upcoming seminar dates and speakers are available here.
As part of their educational efforts, the Center offers a seminar series investigating current topics ranging from the basic biology of DNA replication and repair to our current understanding of how defects in these pathways drive cancer initiation, progression, and response to chemotherapy and immunotherapy. Currently, the Genome Maintenance and Cancer or GMaC virtual seminar series is offered through spring 2022 and features distinguished clinician and basic scientist speakers from around the world. Details about upcoming seminar dates and speakers are available here.
Plans are currently underway for the Center for Genome Integrity’s inaugural spring retreat in April 2022. “Our plan is to continue to grow,” comments Vindigni. “By fostering these collaborations between School of Medicine clinicians and basic scientists, our goal is to establish the Center as a worldwide hub for genome integrity research.”