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Uday Tak

Uday Tak

Assistant Professor, Microbiology, Immunology, and Cancer Biology

Bio & Overview

My laboratory studies the biological conflict between bacteria and the viruses that infect them: bacteriophages (phages). Bacteriophages are the most abundant entity on the planet, and are crucial for controlling bacterial populations, mediating cellular conflict, and evolving virulence factors in pathogens. Consequently, bacteria have evolved an arsenal of sophisticated innate immune systems (defense systems) that sense and neutralize phage replication, allowing them to survive and proliferate in diverse environments including human hosts. Several of these defense systems are evolutionary ancestors of eukaryotic immune systems including the cGAS-STING pathway, and offer mechanistic and evolutionary insight into the origins of antiviral innate immune signaling. In other cases, these predicted systems are entirely unique to bacteria, and represent new biological paradigms that are waiting to be discovered. We use an interdisciplinary approach including but not limited to molecular microbiology, biochemistry, electrophysiology, structural biology, fluorescence microscopy, membrane reconstitution, computational modeling, and bioinformatics. Our work has broad application ranging from uncovering fundamental principles of antiviral immunity shared between bacteria and humans, enhancing the efficacy of phage-based therapeutics to treat antibiotic-resistant infections, and identification of novel enzymes and chemical signals that can be engineered into immunotherapy to diagnose and treat human diseases. Currently the laboratory is interested in the following areas: I) Nucleic acid signaling systems in bacterial antiphage immunity and physiology II) Evolution and mechanisms of programmed cell death and innate immunity III) Bacteriophage isolation and virology IV) Engineering bacterial immune machinery into biotechnology to advance human health

Academic Information

Department
Microbiology, Immunology, and Cancer Biology

Primary Education

  • BS, Biochemistry, Stony Brook University, 2011
  • PhD, Microbiology, University of Alabama Birmingham, 2020
  • Postdoc, Microbiology / Biochemistry, University of Colorado Boulder, 2024

Research Interests

Prokaryotic immune systems, bacteriophage virology, programmed cell death, pore-forming proteins, evolution of immunity, cGAS-STING, protein engineering

Research Disciplines

  • Biochemistry
  • Biology
  • Biophysics
  • Biophysics & Structural Biology
  • Biotechnology
  • Computational Biology
  • Genetics
  • Immunology
  • Microbiology
  • Molecular Biology
  • Molecular Physiology and Biological Physics
  • Molecular and Cellular Physiology
  • Structural Biology

Research Opportunities

  • Biochemistry
  • Biophysics & Structural Biology
  • Biotechnology
  • Immunology
  • Microbiology
  • Molecular Biology

PhD Programs

  • Microbiology

Selected Publications

2026

Tak U, Schinkel K, Holguin-Walth P, Tay J, Hartwick E, Whiteley AT. Bacterial 2′,3′-cGAMP activates a SAVED effector to form membrane-disrupting filaments that restrict phage replication. Cell Host & Microbe. 2026.* https://doi.org/10.1016/j.chom.2026.03.004

*Highlighted in preview article by Wang M and Sternberg S, ‘Insane in the membrane’: 2’3’-cGAMP triggers filamentous phage defense. Cell Host & Microbe 2026 https://doi.org/10.1016/j.chom.2026.03.009

2025

Nguyen A, Bunch Z, Martinez-Aldino I, Rangel-Grimaldo M, Tak U, Thorstenson JC, Severn M, Nakatsuji T, Gallo RL, Graf TN, Oberlies NH, Chekan JR, Cech NB, Horswill AR. The antimicrobial daptide from human skin commensal Staphylococcus hominis protects against skin pathogens. Nature Communications. 2025. https://doi.org/10.1038/s41467-025-66259-w

Sullivan AE, Nabhani A, Schinkel K, Dinh DM, Duncan ML, Ednacot EMQ, Hoffman CRK, Izrailevsky DS, Kibby EM, Nagy TA, Nguyen CM, Tak U, Burroughs AM, Aravind L, Whiteley AT, Morehouse BR. The Panoptes system uses decoy cyclic nucleotides to defend against phage. Nature. 2025. https://doi.org/10.1038/s41586-025-09557-z

2021

Pajuelo D, Tak U, Zhang L, Danilchanka O, Tischler AD, Niederweis M. Toxin secretion and trafficking by Mycobacterium tuberculosis. Nature Communications. 2021; doi: 10.1038/s41467-021-26925-1.

Spencer BL, Tak U, Mendonça JC, Nagao PE, Niederweis M, Doran KS. A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence. PLoS Pathogens. 2021; doi: 10.1371/journal.ppat.1010121. PMID: 34871327.

Tak U, Dokland T, Niederweis M. Pore-forming Esx proteins mediate toxin secretion by Mycobacterium tuberculosis. Nature Communications. 2021; doi: 10.1038/s41467-020-20533-1.

2019

Tak U, Vlach J, Garza-Garcia A, William D, Danilchanka O, de Carvalho LPS, Saad JS, Niederweis M. The tuberculosis necrotizing toxin is an NAD+ and NADP+ glycohydrolase with distinct enzymatic properties. Journal of Biological Chemistry. 2019; doi: 10.1074/jbc.RA118.005832.

2018

Pajuelo D, Gonzalez-Juarbe N, Tak U, Sun J, Orihuela CJ, Niederweis M. NAD+ depletion triggers macrophage necroptosis, a cell death pathway exploited by Mycobacterium tuberculosis. Cell Reports. 2018; doi: 10.1016/j.celrep.2018.06.042.