Faculty & Staff
Alexey Veraksa, PhD
Areas of Expertise
Cell Signaling and Gene Regulation in Development
PhD, Developmental Biology, University of California, San Diego, La Jolla, CA, 2000
MS, Molecular Biology, Moscow State University (MGU), Moscow, Russia, 1994
Professional Publications & Contributions
2012-Present: Associate Professor, Department of Biology, University of Massachusetts Boston.
2005-2012: Assistant Professor, Department of Biology, University of Massachusetts Boston.
2000-2005: Postdoctoral Fellow, MGH Cancer Center and Department of Cell Biology, Harvard Medical School.
1994-2000: Doctoral Research, University of California, San Diego, Department of Biology, and Yale University, Department of Biology.
Awards and Honors
2002-2003: MGH Fund for Medical Discovery Postdoctoral Fellowship
1995-2000: Howard Hughes Medical Institute Predoctoral Fellowship
The long term goal of our research is to investigate the mechanisms that control cell communication during metazoan development. Dysregulation of these control mechanisms results in developmental abnormalities and is the cause of multiple human diseases. Understanding the ways that cells use to route intracellular signals holds a promise of bringing us closer to relevant therapies and being able to create new cellular functions with desired properties.
In the past decade, the study of developmental signaling pathways has been transformed from mapping linear chains of events to exploring the connections between interacting networks. My laboratory is applying the tools of network biology to the analysis of developmental signaling pathways. Our studies of developmental signaling networks are facilitated by using Drosophila as an experimental system. The strength of our approach lies in the integration of proteomics methods with an immediate functional validation carried out in the same laboratory.
Current research projects in the lab are:
1. Control of developmental signaling by β-arrestin.
In order to study the properties of developmental signaling networks, one needs to find a suitable model network of regulators that would be amenable to both biochemical and in vivo analysis. Of a particular interest, from the point of view of regulatory mechanisms, are protein adaptors and scaffolds that associate with specific signaling components and control the routing, duration, and amplification of signals inside the cells. β-arrestins have recently emerged as such intracellular regulators. These proteins have been implicated in the regulation of several developmentally important signaling pathways. We are using the Drosophila β-arrestin Kurtz (Krz) to investigate a fascinating unresolved question: how a single β-arrestin can regulate a set of seemingly unrelated signaling networks. Results from these studies suggest that there are indeed distinct modes of control exerted by Krz on intracellular signaling, but also mechanisms that may link together different signaling pathways. Specifically, we are analyzing the role of Krz in receptor tyrosine kinase (RTK) signaling, focusing on the molecular interactions between Krz and the MAP kinase ERK. We are also studying the involvement of Krz in the regulation of the NF-κB network, which controls early embryo development and larval hematopoiesis in Drosophila. This project is funded by the National Science Foundation.
2. Development of new methods for efficient analysis of protein interactions.
Network analysis begins with an establishment of a network map that provides a global view of the interacting components and identifies connections between them. Isolation of protein complexes from cells and their subsequent analysis by mass spectrometry has become a favorite approach to studying protein interaction networks. Advances in mass spectrometry have enabled a reliable identification of proteins at minute levels. However, the methods to isolate native protein complexes of sufficient purity have lagged behind.
We have previously applied tandem affinity purification (TAP) to the analysis of protein interaction networks in Drosophila. More recently, using genetic and biochemical experiments in flies, we showed that an improved version of the protein purification tag, called the GS-TAP tag, preserves the in vivo function of the tagged proteins and results in higher yields of purified complexes while at the same time reducing the amounts of contaminants. We are distributing the Drosophila GS-TAP vectors to the scientific community and are now developing even more efficient ways to purify protein complexes and analyze protein interaction networks.
3. In vivo analysis of signaling dynamics in the Notch interaction network.
The Notch signaling pathway plays a critical role in multiple cell fate decision events in metazoans. In recent years, Notch has been implicated in the pathology of cancer in humans, both as an oncogene and as a tumor-promoting factor that cooperates with other signals to cause neoplasia. Genetic and biochemical evidence has revealed a large network of modulators that are involved in establishing a precise level of Notch signaling and determining tissue-specific outcomes of pathway activation, from the interaction of the Notch receptor with its ligands Delta and Serrate to transcriptional regulation of the Notch target genes. Despite considerable progress in identifying Notch pathway regulation, a major obstacle has been inability to study endogenous signaling events.
We have established a collaboration with the laboratory of Spyros Artavanis-Tsakonas (Department of Cell Biology, Harvard Medical School) to investigate the in vivo signaling dynamics in the Notch pathway. In this project, we are using the genetic advances in recombineering and targeted transgene insertions to replace the endogenous Notch and Delta genes with their fluorescent and affinity tagged isoforms. These transgenes are used for studying the composition of Notch containing signaling complexes and for imaging the process of Notch activation in vivo. Completion of these experiments will establish an in vivo map of the Notch interaction network and reveal the dynamics of signaling in living cells. This project has been funded by the collaborative NIH U54 grant to UMass Boston and Dana-Farber/Harvard Cancer Center.