Daniel Cifuentes, Ph.D.
Assistant Professor of Biochemistry and Microbiology
71 east Concord Street, K420
Lab: Office: 617-358-4520
B.S. University of Barcelona
Ph.D. University of Barcelona
Cifuentes lab website
Our research goals in the Cifuentes laboratory aim to understand the molecular mechanisms of RNA regulation. In particular, we focus on the study of RNA-binding proteins, microRNAs, and RNA modifications to uncover their impact on small RNA biogenesis and mRNA post-transcriptional regulation. To address these goals, the lab combines high-throughput genetic, genomic, and proteomic approaches applied to two independent but technically interconnected areas: vertebrate development and viral replication, using zebrafish and filoviruses as primary model systems.
Role of post-transcriptional regulation during vertebrate embryogenesis:
The beginning of a new life is one of the most enigmatic and dynamic events in Biology. Right after fertilization, multiple cell division occur without any contribution of the transcriptionally silent genome. Therefore, the first embryonic processes are organized at post-transcriptional level. Our laboratory focuses on the study of how small RNA and RNA-binding proteins regulate mRNA stability and decay. To this end, we use zebrafish as a model system to dissect the process of post-transcriptional reprogramming within the context of a whole organism. The combination of fish embryo microinjections, together with powerful genetic, genomic, and proteomic approaches provides a unique platform to address this central question in biology.
Regulation of transcription, replication and translation in RNA viruses:
Filovirus and Arenavirus belong to the group of Viruses of Concern (VOCs) with epidemic and pandemic potential as identified by the World Health Organization. Their common feature is that these viruses have an RNA genome, and as such, RNA regulation take center stage in orchestrating the infection cycle of these viruses. In our laboratory, we investigate 1) how small RNAs and RNA binding protein govern the balance between transcription and replication in Filovirus (Ebola and Marburg virus) and 2) how secondary RNA structures and cellular factors regulate translation of viral mRNAs in Arenavirus (Lassa virus). To this end, we capitalize in our long-standing collaboration with the group of Prof. Mühlberger at the National Emerging Disease Laboratory (NEIDL) at Boston University.
- Hume AJ, Heiden B, Olejnik J, Suder EL, Ross S, Scoon WA, Bullitt E, Ericsson M, White MR, Turcinovic J, Thao TTN, Hekman RM, Kaserman JE, Huang J, Alysandratos KD, Toth GE, Jakab F, Kotton DN, Wilson AA, Emili A, Thiel V, Connor JH, Kemenesi G, Cifuentes D, Mühlberger E. Recombinant Lloviu virus as a tool to study viral replication and host responses. PLoS Pathog. 2022 02; 18(2):e1010268.PMID: 35120176.
- Hekman RM, Hume AJ, Goel RK, Abo KM, Huang J, Blum BC, Werder RB, Suder EL, Paul I, Phanse S, Youssef A, Alysandratos KD, Padhorny D, Ojha S, Mora-Martin A, Kretov D, Ash PEA, Verma M, Zhao J, Patten JJ, Villacorta-Martin C, Bolzan D, Perea-Resa C, Bullitt E, Hinds A, Tilston-Lunel A, Varelas X, Farhangmehr S, Braunschweig U, Kwan JH, McComb M, Basu A, Saeed M, Perissi V, Burks EJ, Layne MD, Connor JH, Davey R, Cheng JX, Wolozin BL, Blencowe BJ, Wuchty S, Lyons SM, Kozakov D, Cifuentes D, Blower M, Kotton DN, Wilson AA, Mühlberger E, Emili A. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Mol Cell. 2021 Jan 07; 81(1):212. PMID: 33417854
- Kontur C, Jeong M, Cifuentes D, Giraldez AJ. Ythdf m6A Readers Function Redundantly during Zebrafish Development. Cell Rep. 2020 Dec 29; 33(13):108598. PMID: 33378672;
- Kretov DA, Walawalkar IA, Mora-Martin A, Shafik AM, Moxon S, Cifuentes D. Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis. Mol Cell. 2020 Apr 16; 78(2):317-328.e6. PMID: 32191872
- Vejnar CE, Abdel Messih M, Takacs CM, Yartseva V, Oikonomou P, Christiano R, Stoeckius M, Lau S, Lee MT, Beaudoin JD, Musaev D, Darwich-Codore H, Walther TC, Tavazoie S, Cifuentes D*, Giraldez AJ*. Genome wide analysis of 3′ UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish. Genome Res. 2019 07; 29(7):1100-1114. PMID:31227602
- Kretov DA, Shafik AM, Cifuentes D. Assessing miR-451 Activity and Its Role in Erythropoiesis. Methods Mol Biol. 2018; 1680:179-190. PMID: 29030849
- Vejnar CE, Moreno-Mateos MA, Cifuentes D, Bazzini AA, Giraldez AJ. Optimization Strategies for the CRISPR-Cas9 Genome-Editing System. Cold Spring Harb Protoc. 2016 Oct 03; 2016(10):pdb.top090894. PMID: 27698246.
- Hoffman EJ, Turner KJ, Fernandez JM, Cifuentes D, Ghosh M, Ijaz S, Jain RA, Kubo F, Bill BR, Baier H, Granato M, Barresi MJ, Wilson SW, Rihel J, State MW, Giraldez AJ. Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2. Neuron. 2016 Feb 17; 89(4):725-33. PMID: 26833134.
- Yoda M, Cifuentes D, Izumi N, Sakaguchi Y, Suzuki T, Giraldez AJ, Tomari Y. Poly(A)-specific ribonuclease mediates 3′-end trimming of Argonaute2-cleaved precursor microRNAs. Cell Rep. 2013 Nov 14; 5(3):715-26. PMID: 24209750.
- Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi Y, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh JR, Joung JK. Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods. 2011 Jan; 8(1):67-9. PMID: 21151135.
- Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson ND, Wolfe SA, Giraldez AJ. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science. 2010 Jun 25;328(5986):1694-8. PMID: 20448148