David Yu Zhang
Ted Law Jr. Assistant Professor of Bioengineering
Postdoctoral Fellow, Wyss Institute for Biologically Inspired Engineering,
Harvard Medical School (2010-2013)
Ph.D. Computation and Neural Systems, California Institute of Technology (2010)
B.S. Biology, California Institute of Technology (2005)
David Yu Zhang leads the Nucleic Acid Bioengineering Laboratory (NABLab) at Rice University's BioScience Research Collaborative. His investigations involve the systematic modeling and rational design of nucleic acids, such as DNA and RNA. Zhang is particularly interested in understanding how natural nucleic acids behave, and in the engineering of designer nucleic acid molecules that enable revolutionary in vitro diagnostics, in situ imaging, tissue engineering, transcription regulation, and materials scaffolding and modulation.
Prior to joining the Rice bioengineering program in 2013, Zhang worked as a postdoctoral scholar in the laboratory of Assistant Professor Peng Yin at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School. While at Harvard, Zhang’s efforts to develop versatile and ultra-specific bio-imaging tools from DNA and RNA for biomedical application were supported by two nationally competitive research fellowships: a K99/R00 Pathway to Independence Award by the National Institutes of Health (2012), and a Life Sciences Research Foundation award from the Howard Hughes Medical Institute (2010). One of the results of Zhang’s postdoctoral research is the development of ultraspecific DNA and RNA hybridization probes that robustly discriminate single nucleotide polymorphisms (SNPs) across a wide range of temperatures and salinities. Zhang is currently collaboratively pursuing the application of these probes in genetics, developmental biology, and point-of-care diagnostics.
Zhang completed both his graduate and undergraduate studies at the California Institute of Technology with the majority of his time working in Professor Erik Winfree’s research group. Zhang’s graduate research into the development of DNA-based catalysts for dynamic strand displacement circuits was funded by a five-year fellowship from the prestigious Fannie and John Hertz Foundation. One of the major results of Zhang's graduate work is the development of isothermal, enzyme-free nucleic acid amplification methods. This biophysics based method for improving the sensitivity of nucleic acid diagnostics excels in not requiring special buffer conditions or temperature cycling typically needed for PCR.
His work has led to three awarded U.S. patents and five pending U.S. and international patents. Zhang’s graduate and postdoctoral research have been featured in 17 journal publications, including: Synthetic DNA analogs of microtubules that grow in solution (Nature Communications 2013, accepted); Rifampicin resistance assays using double-stranded DNA probes (Nature Chemistry 2013, in revision); Robust and ultraspecific DNA probes and primers for SNP detection (Nature Chemistry 2012); A comprehensive review of dynamic DNA nanotechnology (Nature Chemistry 2011); An analog concentration comparison mechanism for nucleic acids (J. Am. Chem. Soc. 2011); A predictive quantitative model of nucleic acid reconfiguration kinetics (J. Am. Chem. Soc. 2009); An experimentally validated design strategy for allosteric DNA molecules (J. Am. Chem. Soc. 2008); Cascaded enzyme-free nucleic acid amplification methods (Science 2007); and Synthetic nucleic acid logic circuits (Science 2006).
The Nucleic Acid Bioengineering Laboratory (NABLab) is currently pursuing three main lines of research:
- NABLab is interested in improving the science of DNA and RNA folding. Accurate in silico prediction of DNA and RNA secondary and tertiary structure from sequence is needed to enable reliable targeting of RNA interference and understanding of alternative splicing. Current algorithms and parameters are lacking in both accuracy and capacity, yielding only 40-60 percent accuracy and are typically limited to analyzing non-pseudoknotted nucleic acids of less than 500 nucleotides in length. NABLab takes a combined chemistry and computer science approach to revolutionizing this field: novel non-covalent catalysis techniques enable high-precision measurements of nucleic acid hybridization thermodynamics of hybridization motifs at native conditions, and novel divide-and-conquer dynamic programming algorithms significantly increase the length of sequences that can be quickly folded.
- NABLab is interested in the development of clinical diagnostic tools and devices based on analysis of circulated DNA and RNA. Nucleic acids are signature molecules of life, and almost all diseases possess some nucleic acid component that could potentially be used as a biomarker. Specifically, recent research has shown that a surprisingly large (1000+) number of cancer-specific nucleic acid molecules exist in each mL of blood, for even early stage colorectal and pancreatic cancer patients. NABLab is developing ultraspecific and ultrasensitive enzyme-free methods of discriminating and amplification nucleic acid biomarkers; the development of reliable enzyme-free disease diagnostics could enable frequent non-invasive screens, such as for home or primary care use.
- NABLab is interested in the development of nucleic acid-based molecular research tools. Nucleic acids play vital roles in biology not only as genetic information storage media, but also as active components that regulate the expression of genes. Consequently, there is intense interest from many subfields of genetics and developmental biology in the spatial and temporal distributions of specific nucleic acids. NABLab is developing molecular tools to help the study of the biological roles of nucleic acids, such as conditionally fluorescent probes for in situ hybridization and ultraspecific primers for PCR.
NABLab is currently looking to expand, and welcomes inquiries from prospective postdoctoral scholars, graduate students, and undergraduate students. Please see the NABLab webpage for more details.