The extracellular matrix (ECM) is a fundamental component of multicellular organisms that provides mechanical and chemical cues that orchestrate cellular and tissue organization and functions. Degradation, hyper-production or alteration of the composition of the ECM cause or accompany numerous pathologies such as musculo-skeletal and cardio-vascular diseases, cancers, and fibroses. Thus, a better characterization of ECM composition, metabolism, and biology can lead to the identification of novel prognostic and diagnostic markers and therapeutic opportunities. In the first part of my talk, I will describe our latest advances in bioinformatics and mass-spectrometry-based proteomics to define the in silico and in vivo “matrisome” of normal and diseased tissues. I will then discuss how these approaches can be used to characterize the ECM composition of normal and diseased samples and lead to the identification of 1) novel proteins playing causal role in the etiology of diseases, and 2) ECM biomarkers distinguishing normal and diseased tissues and of prognostic value to patients. In the last part of my talk, I will discuss our latest effort aimed at building an ECM Atlas, a compendium of proteomic data on the ECM of normal and diseased tissues, with an emphasis on data from studies of samples from human patients and murine models of cancers and fibroses.
Alexandra received her Ph.D. from the Curie Institute in Paris, France where she studied the role of the membrane-cytoskeleton linker, ezrin, in normal and tumor cell adhesion.
For her postdoctoral training, Alexandra joined the laboratory of Dr. Richard Hynes at MIT where she led a project aimed at understanding the role of the extracellular matrix (ECM) in tumor progression. The ECM is a requirement and defining characteristic of metazoan life. A handful of ECM molecules are known to make critical contributions to disease processes, but technical limitations have prevented a comprehensive analysis of this critical family of proteins. At MIT, Alexandra overcame these barriers and developed novel proteomics and bioinformatics approaches to study the molecular composition of the ECM, pioneering the field of "matrisomics". Her work demonstrated striking differences in the matrisome of tumors of different metastatic potential and showed that distinct sets of ECM proteins could predict metastatic potential of primary tumors. Furthermore, she found that differentially expressed ECM proteins are required for metastasis in mouse models, presenting the opportunity for novel interventions in cancer. In 2016, together with a team of mass spectrometrists and bioinfomaticians, Alexandra published the first draft of an ECM atlas compiling proteomics data from normal and diseased tissues, and released "The Matrisome Project" website (http://matrisome.org).
Alexandra was appointed Assistant Professor in the Department of Physiology and Biophysics at University of Illinois at Chicago in October 2016. She is also an associate member of the University of Illinois Cancer Center. Her laboratory focuses on deciphering the roles of a novel ECM glycoprotein, SNED1, in breast cancer progression and embryonic development. Her laboratory also continues to develop bioinformatic and proteomic methods to further characterize the ECM.
Alexandra published over 20 peer-reviewed publications and one patent, received numerous travel awards and invitations to speak at national and international conferences.
She serves as a member of the editorial board of Matrix Biology and since 2017, she serves on the council of the American Society for Matrix Biology.
She is the recipient of the 2018 Rupert Timpl award from the International Society for Matrix Biology and the 2018 Junior Investigator award from the American Society for Matrix Biology, recognizing her contributions to extracellular matrix research. She also received in 2018 a Rising Star award from the College of Medicine at the University of Illinois at Chicago.