Home > Seminars > From Yeast to Man: Systems Analyses Advance Therapeutic Development & Drug Discovery in Complex Diseases

From Yeast to Man: Systems Analyses Advance Therapeutic Development & Drug Discovery in Complex Diseases

Start:

4/7/2015 at 3:30PM

End:

4/7/2015 at 4:30PM

Location:

Eck Visitors Center Auditorium

Host:

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Edward Maginn

Edward Maginn

VIEW FULL PROFILE Email: ed@nd.edu
Phone: 574-631-5687
Website: http://www.nd.edu/~ed/
Office: 182A Fitzpatrick Hall

Affiliations

Department of Chemical and Biomolecular Engineering Dorini Family Professor of Energy Studies and Department Chair
College of Engineering Dorini Family Professor of Energy Studies and Chair of the Department of Chemical and Biomolecular Engineering
The research in our group focuses on developing a fundamental understanding of the link between the physical properties of materials and their chemical constitution. Much of our work is devoted to applications related to energy and the environment. The main tool we use is molecular simulation. In ...
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Current challenges in therapeutic development, biopharmaceutical production, and limitations of human disease models motivate our pursuit to understand how cellular processes and molecular interactions perform under systemic perturbations. Systems biology approaches — with their integration of computational, experimental, and observational inquiries — guide the rigorous assessment of regulation at multiple scales. We employ a systems-level understanding to characterize biological networks underlying complex cell behavior including (i) cell stress response pathways of a single-cell organism such as yeast, and (ii) communication networks within 3-D tissues that recapitulate human physiology and disease progression.

As arguably the most well-characterized cellular response promoting homeostasis, the Unfolded Protein Response (UPR) is defined by a coordinated program of transcription that up-regulates genes within the early secretory pathway. In contrast to this classical description, our investigations in S. cerevisiae further indicate that an extensive program of global repression exists, highly enriched in protein synthesis and metabolic functions. DNA recombination strategies combined with high-resolution imaging techniques determined that protein redistribution, resultant spatial effects, and organelle modifications are diverse consequences of UPR activation. The elucidation of these pathways has become of growing importance in therapeutic development, as the UPR has been intimately linked to Alzheimer’s disease, Parkinson’s disease, diabetes, cancer, and inflammation.

Clearly, the complexity of human physiology must be assessed in a more complex environment that accounts for interacting cell types coexisting in a hierarchical 3-D structure. The emergence of organ-on-a-chip microfabricated devices facilitates the study of human physiology in vitro, enabling the development and validation of predictive models in drug discovery. The integration of tissue engineering, primary cell sources, emerging biomaterial strategies, and computational models promoted novel experiments to investigate breast cancer metastasis. As a result, we have identified plausible signatures of human-specific cross-talk between the tumor and hepatic tissues. Ultimately, these results will directly impact clinical prognosis of early metastatic disease while improving drug efficacy and toxicity models of chemotherapies. 

Seminar Speaker:

Carissa L. Young

Carissa L. Young

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA

Carissa Young is a postdoctoral associate at MIT in the Department of Biological Engineering leading integrated systems approaches in biomarker discovery of breast cancer metastasis, liver and lung inflammation. She earned her Ph.D. in Chemical and Biomolecular Engineering at the University of Delaware in 2012 with an emphasis in cellular and protein engineering, and a B.S. in Chemical Engineering from Georgia Tech in 2002. Carissa has 19 publications in the field of biotechnology and is the recipient of a NIH Development award, NSF ADVANCE award, Recombinant DNA Technology award, and Academic and Civic Excellence award. Notably, Carissa has held six teaching appointments in academia and worked within the pharmaceutical industry.

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