Faculty & Staff Directory
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. Regulation of organ growth and tissue patterning via coordinated activities of ERK and Minibrain
The transcriptional repressor Capicua (Cic) is a conserved regulator of organ growth and tissue patterning, and mutations in the CIC gene in humans result in the brain cancer oligodendroglioma. Cic activity is controlled by the receptor tyrosine kinase (RTK)/ERK signaling pathway. We have recently identified the kinase Minibrain (Mnb)/DYRK1A and its adaptor Wings apart (Wap)/DCAF7 as novel Cic regulators that inhibit Cic activity independently from other growth-controlling pathways. Therefore Cic functions as an integrator of multiple upstream signals that converge on this protein to control tissue patterning and organ growth. Our current efforts are directed at elucidating how the activities of these signaling pathways are coordinated in development. This work is relevant for understanding human diseases such as cancer and the Down’s syndrome, given the involvement of human orthologs of Cic and Minibrain (DYRK1A) in these diseases.
2. Signaling functions of the Drosophila β-arrestin Kurtz (Krz)
Our laboratory has made significant contributions to the analysis of signaling functions of the Drosophila β-arrestin Kurtz (Krz). Our previous studies identified Krz as a Notch signaling modulator that regulates the turnover of the Notch receptor. Subsequent work in our laboratory has revealed its role in regulating the receptor tyrosine kinase Torso and Toll/NF-κB signaling pathways in Drosophila embryogenesis. We have found that Krz inhibits ERK signaling by a previously unknown sequestration mechanism. More recently we have shown that Krz plays an important role in controlling immune homeostasis in Drosophila larvae by limiting Toll pathway activity, which occurs via an association of Krz with a SUMO protease, Ulp1. Krz has thus emerged as a signaling hub for several signaling pathways, and we are continuing our studies of its interaction network and roles in the control of developmental signaling.
3. New insights into the Hippo pathway
Our laboratory has identified important novel regulators of the Hippo/Yorkie signaling pathway in Drosophila. The Hippo pathway has emerged as a conserved developmental mechanism responsible for the regulation of organ growth. Novel regulators of this pathway identified in our laboratory in proteomics experiments have been biologically validated in collaborative work with the Moberg and Harvey labs. We are continuing our studies of the Hippo pathway and the biological characterization of novel components.
4. Developmental proteomics
Our laboratory is continually developing efficient methods to purify and analyze developmentally important signaling complexes. We have applied affinity purification-mass spectrometry (AP-MS) approaches to the analysis of developmental signaling in Drosophila. We have used this methodology to study the Notch signaling pathway, as well as signaling via the receptor tyrosine kinase/ERK and Hippo/Yorkie pathways. Our expertise in the area of developmental proteomics has resulted in a number of productive collaborations. We also serve the scientific community by distributing DNA vectors for use in protein tagging and purification, as well as by sharing proteomics expertise.