BME Adds New Research Area: Systems Biology

Last year, the Department of Biomedical Engineering added a sixth area of specialization: systems biology. Systems biology is the integration of experimental and modeling approaches to dissect complex cellular phenomena. Fundamentally, systems biologists aim to better quantify and comprehend the highly multivariate and interactive networks of genes, proteins, and metabolites that regulate cellular function. Our faculty apply new experimental and computational approaches to understand how these transcriptional, signal transduction, and metabolic networks are regulated in healthy tissues and how they become dysregulated in pathological settings such as cancer and aging. Our researchers use modeling efforts to better engineer both novel biomolecules and new combinatorial therapeutic strategies to treat these pathophysiologies. Increasingly, our efforts aim to merge experiment and modeling at the single-cell level so as to elucidate how cell-to-cell variability arises and underlies disease progression and response to therapy. As such, we are involved in the development of sensitive approaches capable of multiplexed, quantitative measurement with single-cell resolution. These efforts rely on connections with Cornell’s Nanobiotechnology Center, Center on the Microenvironmental and Metastasis (an NIH-funded Physical Sciences Oncology Center), and Stem Cell Program, as well as in collaborations with clinical and research scientists at Weill Cornell Medical College.

Systems Biology Faculty:

Ben Cosgrove
Ben Cosgrove’s lab studies how aging influences a decline in the ability of resident stem cells to regenerate adult tissues. His lab explores how alterations in both the tissue microenvironment and cell signal transduction pathways within the stem cells themselves are altered in aging. His research uses computational and experimental approaches to better understand multivariate interactions in these signaling networks and to target aberrant network functions to rejuvenate stem cells in aged tissues. 

Read more:
B.D. Cosgrove, P. M. Gilbert, E. Porpiglia, F. Mourkioti, S. P. Lee, S. Y. Corbel, M. E. Llewellyn, S. L. Delp, H. M. Blau. 2014. “Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.” Nature Medicine 20 (3): 255-264. 
Cosgrove, Ben, L. G. Alexopoulos, T. Hang, B. S. Hendriks, P. K. Sorger, L. G. Griffith, D. A. Lauffenburger. 2010. “Cytokine-associated drug toxicity in human hepatocytes is associated with signaling network dysregulation.” Molec BioSyst 6 (7): 1195-206.

Iwijn De Vlaminck
Iwijn De Vlaminck leads an experimental physical genomics lab focused on the development and application of sensitive single-cell genome sequencing principles. Single-cell sequencing enables highly multivariate measurements of genomic and transcriptomic cell-to-cell variability. When combined with microscopy techniques, single cell sequencing will enable the study of the systems biology of cells in tissue microenvironments.

The De Vlaminck lab uses high throughput sequencers as molecular counters of circulating cell-free DNA to diagnose infection and rejection in organ transplantation. Top: A transplant can be thought of as a genome transplant, since each cell in the donor organ has a different genome than the recipient. Cell death in the graft consequently leads to the release of DNA that can be discriminated from recipient DNA via genomic analyses. Bottom: representation of different viral families in plasma of heart and lung transplant recipients as function of time after transplantation.

Read more:
De Vlaminck, Iwijn, Hannah A. Valentine, Thomas M. Snyder, Calvin Strehl, Cohen Garrett, Helen Luikart, Norma E. Neff, Jennifer Okamoto, Daniel Bernstein, Dana Weisshaar, Stephen R. Quake, Kiran K Khush. 2014. “Quantification of circulating donor-specific cell-free DNA for detection of heart transplant injury.” Science Transitional Medicine 6 (241ra77).
Bourcy, Charles de, Iwijn De Vlaminck, Jianbin Wang, Jad Kanbar, Charles Gawad, Stephen R. Quake. 2014. “Quantitative Comparison of Single-Cell Whole Genome Amplification Methods.” PLOS ONE 9 (e105585).

Systems Biology Field Faculty

Jesse Goldberg is an assistant professor in the department of Neurobiology and Behavior. His lab is interested in how systems of interconnected brain regions interact to control behavior. 

Jason Locasale is an assistant professor in the department of Nutritional Science. His lab focuses on an integrated understanding of metabolism in health and disease. 

Julius Lucks is a James C. and Rebecca Q. Morgan Sesquicentennial Faculty Fellow in the department of Chemical and Biomolecular Engineering. His lab is interested in the bottom-up design and construction of sophisticated genetic systems with predictable function. 

Jeffrey Varner is an associate professor in the department of Chemical and Biomolecular Engineering. His research focuses on the development of physiochemical modeling tools that can be used to rationally “reprogram” signal flow in human signal transduction networks.