Joshua Wetzel

Computer Scientist/Computational Biologist
Lewis-Sigler Institute for Integrative Genomics
Princeton Univiversity
Laboratory of Professor Mona Singh

Research Interests

Broadly, I am interested in biological interactions at the molecular level, and understanding how cells "know" what to do and when to do it. In particular, I am keen to study the role of variation and plasticity in macromolecular interactions (especially protein-DNA interactions) in giving rise to vast diversity not only at evolutionary timescales, but also across individuals within a single species.

Recently, my work has focused on elucidating the regulatory roles of proteins containing Cys2-His2 zinc finger (C2H2-ZF) DNA-binding domains. Although this is the most abundant family of DNA-binding proteins found in complex organisms, containing members known to be crucial to critical biological processes (e.g., cell-fate detemination, guidance of meiotic recombination, chromatin loop formation, and silencing transposable genetic elements), it is also the most poorly understood (see review). The majority of C2H2-ZFs appear to be able to bind DNA in a sequence-specific fashion, yet reliable experimental determination of their intrinsic DNA-binding specificities has been particularly elusive. My goal is to further our understanding of the determinants of C2H2-ZF protein-DNA interactions via innovative computational methods that marry information obtained from high-throughput physical interaction screens, high resolution co-complex structures, and various other genomic datasets. Hopefully this work will allow a more complete picture of not only how C2H2-ZFs determine their DNA targets, but also of the particular biological functions that their binding modulates.

Previously ...

I received my Ph.D. in Computer Science from Princeton Unversity, where I was advised by Professor Mona Singh. My dissertation work focused on development of computational approaches to improve prediction and understanding of DNA-binding specificities of transcription factor proteins.

I received my BS in Computer Science from Rutgers, The State University of New Jersey, where Rajiv Gandhi was my undergraduate mentor. I also held a summer undergraduate research internship position at the Center for Bioinformatics and Computational Biology, University of Maryland, College Park, under the mentorship of Mihai Pop and Carl Kingsford . There, I did work exploring the theoretical limitations of using shotgun sequencing data to build accurate de novo genome assemblies.

Publications

Anton V. Persikov*, Joshua L. Wetzel*, Elizabeth F. Rowland, Benjamin L. Oakes, Denise J. Xu, Mona Singh, and Marcus B. Noyes. A systematic survey of the Cys2His2 zinc finger DNA-binding landscape. Nucleic Acids Res. 2015; 43(3):1965-1984.
*Contributed equally as co-first authors.

Henry C Lin, Steve Goldstein, Lee Mendelowitz, Shiguo Zhou, Joshua Wetzel, David C Schwartz, Mihai Pop. AGORA: Assembly Guided by Optical Restriction Alignment. BMC Bioinformatics 2012;13:189.

Joshua Wetzel, Carl Kingsford, Mihai Pop. Assessing the benefits of using mate-pairs to resolve repeats in de novo short-read prokaryotic assemblies. BMC Bioinformatics 2011;12:95.

Contact

Princeton Universty
Department of Computer Science
35 Olden St.
Princeton, NJ 08540

jlwetzel[at]cs[dot]princeton[dot]edu