Our lab is interested in how the cells of various types respond to changes in their micro-environment and how they can define their microenvironment to create a medium for communication. Live cells have evolved sophisticated ways to detect external signals robustly, often in a very noisy environment. In particular, they have a system of dedicated coupled chemical reactions (signaling pathways) that convey the information about changing environment from the cell surface sensors (receptors) to the internal decision making ‘machines’, including cell engines (cytoskeleton and motor proteins) and genetic material (by means of transcription factors). It is essential for a cell to perform this signal transduction process in a correct fashion, otherwise its chances of survival rapidly diminish. Frequently, changes in signaling pathways can result in loss of environmental control of cell behavior, making cells ‘blind’. In some cases, unrestricted cell growth can result leading to development of cancer. Signaling pathways are also at the core of cell decisions of how and where to move, whether to change what they do (cell differentiation) or to commit suicide (apoptosis).
Cells can also produce signals, using signaling pathways to detect the presence and understand the messages from cells that are close by (autocrine and paracrine signaling) or far away (endocrine signaling). The resulting collective cell behavior can be quite complex, leading to formation of functional tissues or dysfunction cell ensembles, such as tumors. Sometimes, cells interact in unconventional ways, e.g. by exchanging proteins and cytosolic components through the process related to intercellular proteins transfer.
In our research, we believe that a tight combination of sophisticated computational and experimental approaches is not only feasible but essential for making progress in understanding cell signaling processes at the fundamental level. We therefore perform research in an iterative fashion, generating hypotheses by performing state of the art modeling analysis and then testing these hypotheses using cutting edge experimental technologies leads to a new and exciting way science can be done, in a way that is devoid of the tunnel vision characteristic of some established research paradigms. This implies, that lab researchers are involved in a variety of pursuits, including fabrication and utilization of novel micro- and nano-scale devices for cell imaging, analysis and archiving of the imaging data, use of experimental data to develop and improve computational models of complex computational models, analysis of the models to reveal their unique properties, development of more theoretical approaches to understand how cell interact with their environment.
In this work we are motivated by important biological questions, including but not limited to cell responses to chemical gradients, oscillations and switches in signaling pathways, properties of bacterial-host interactions, differentiation of stem cells, control of cell shape, polarity and cell division. Our findings have implications for understanding of the development of the immune response, progression of cancer, various bacterial infections, wiring of the brain tissue and treatment modalities using stem cells.
The lab benefits from membership in various inter-departmental efforts, including lab space and facilities in the Whitaker Institute for Biomedical Engineering, and the Institute for Cell Engineering and participation in the efforts of the Institute for Multiscale Modeling of Biological Interactions and Institute for Computational Medicine. We are also a part of the Hopkins National Technology Center for Networks and Pathways. We are collaborating with various other labs both inside and outside Johns Hopkins, including labs headed by Alex Groisman, Ann Stevens, Alex Hoffmann, Pablo Iglesias, Andy Feinberg, Gregg Semenza. Guo-li Ming, Henrik Johnsson, Kyle Cunningham, Peter Devreotes, Steven Disederio, Jeff Boeke, Steven Larson, Kaph-Yang Suh and Merav Socolovsky.
Please, explore this web page, as it contains a variety of more detailed information on our research pursuits and also some fun we have on the way.