Research Overview

Protein interaction networks are at the heart of cellular decision making, both in health and disease. Our laboratory uses approaches from biomolecular engineering, synthetic biology, and systems biology to elucidate how protein networks drive a number of developmental and disease-relevant processes, including stem cell differentiation, dormancy induction in cancer, and progression of neurodegenerative diseases.

At a fundamental level, we are particularly interested in elucidating how these protein networks can engender different decisions among individual cells in a population and also how they enable cells to resolve conflicting cues in their environment. Our understanding of how a protein network interfaces with environmental cues also has translational applications in the design of more effective protein and cellular therapeutics.

Using a powerful method known as directed evolution, we can rapidly engineer novel proteins in the laboratory to block or activate key network nodes to modulate the corresponding cell response, such as inhibiting proliferation in cancer. We also construct entirely new protein networks in therapeutic cells with the goal of exploiting such living therapies to enable dynamic drug delivery responses, as is needed, for example, in insulin dosing for diabetics.

Education

• BS, Chemical Engineering, University of Texas, Austin, 1997
• PhD, Chemical Engineering, Massachusetts Institute of Technology, 2002
• Postdoctoral Fellow, Biochemistry, University of Zurich, 2002-2005

Honors and Awards

2011-2016 - CAREER Award, National Science Foundation

2008-2012 - Scientist Development Grant, American Heart Association

2003-2005 - NRSA Postdoctoral Fellowship, National Institutes of Health

1997 - Graduate Fellowship, Howard Hughes Medical Institute (declined)

1997 - Graduate Fellowship, National Science Foundation (declined)

1997 - Graduate Fellowship, Whitaker Foundation (declined)

1997-2002 - Graduate Fellowship, Fannie and John Hertz Foundation (accepted)

Selected Publications

N.A. Shah, M. Levesque, A. Raj, and C.A. Sarkar. "Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue." Journal of Cell Science, 128:3009-3017 (2015).

I. Dodevski, G.C. Markou, and C.A. Sarkar. "Conceptual and methodological advances in cell-free directed evolution." Current Opinion in Structural Biology, 33:1-7 (2015).

N.A. Shah and C.A. Sarkar. "Computationally guided design of robust gene circuits." Methods in Molecular Biology, 1244:167-178 (2015).

D.T.W. Ng and C.A. Sarkar. "NP-Sticky: a web server for optimizing DNA ligation with non-palindromic sticky ends." Journal of Molecular Biology, 426:1861-1869 (2014).

M.S. Magaraci, A. Veerakumar, P. Qiao, A. Amurthur, J.Y. Lee, J.S. Miller, M. Goulian, and C.A. Sarkar. "Engineering Escherichia coli for light-activated cytolysis of mammalian cells." ACS Synthetic Biology, 3:944-948 (2014).

H.M. Mehta, M. Futami, T. Glaubach, Q. Yang, D.W. Lee, J.R. Andolina, Z. Whichard, M. Quinn, H. Lu, W.-M. Kao, B. Przychodzen, C.A. Sarkar, A. Minella, J.P. Maciejewski, and S.J. Corey. "Alternatively spliced, truncated GCSF receptor promotes leukemogenic properties and sensitivity to JAK inhibition." Leukemia, 28:1041-1051 (2014).

C.A. Sarkar. "Concentrating (on) native proteins to control cell fate." Science, 341:1349-1351 (2013).

P.A. Barendt, N.A. Shah, G.A. Barendt, P.A. Kothari, and C.A. Sarkar. "Evidence for context-dependent complementarity of non-Shine-Dalgarno ribosome binding sites to Escherichia coli rRNA." ACS Chemical Biology, 8:958-966 (2013).

P.A. Barendt, D.T.W. Ng, C.N. McQuade, and C.A. Sarkar. "Streamlined protocol for mRNA display." ACS Combinatorial Science, 15:77–81 (2013).

D.T.W. Ng and C.A. Sarkar. "Engineering signal peptides for enhanced protein secretion from Lactococcus lactis." Applied and Environmental Microbiology, 79:347-356 (2013).

S.T. Jung, W. Kelton, T.H. Kang, D.T.W. Ng, J.T. Andersen, I. Sandlie, C.A. Sarkar, and G. Georgiou. "Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high FcγRIIa affinity and selectivity." ACS Chemical Biology, 8:368-375 (2013).

D.T.W. Ng and C.A. Sarkar. "Model-guided ligation strategy for optimal assembly of DNA libraries." Protein Engineering, Design, and Selection, 25:669-678 (2012).

P.A. Barendt, N.A. Shah, G.A. Barendt, and C.A. Sarkar. "Broad-specificity mRNA-rRNA complementarity in efficient protein translation." PLOS Genetics, 8:e1002598 (2012).

S. Palani and C.A. Sarkar. "Transient noise amplification and gene expression synchronization in a bistable mammalian cell-fate switch." Cell Reports, 1:215-224 (2012).

E.C. O'Shaughnessy and C.A. Sarkar. "Analyzing and engineering cell signaling modules with synthetic biology." Current Opinion in Biotechnology, 23:785-790 (2012).

N.A. Shah and C.A. Sarkar. "Robust network topologies for generating switch-like cellular responses." PLOS Computational Biology, 7:e1002085 (2011).

S. Palani and C.A. Sarkar. "Synthetic conversion of a graded receptor signal into a tunable, reversible switch." Molecular Systems Biology, 7:480 (2011).

D.T.W. Ng and C.A. Sarkar. "Nisin-inducible secretion of a biologically active single-chain insulin analog by Lactococcus lactis NZ9000." Biotechnology and Bioengineering, 108:1987-1996 (2011).

E.C. O'Shaughnessy, S. Palani, J.J. Collins, and C.A. Sarkar. "Tunable signal processing in synthetic MAP kinase cascades." Cell, 144:119-131 (2011).