Haoquan Wu, Ph.D.
Assistant Professor of the Center of Excellence in Infectious Diseases
Department of Biomedical Sciences
Center of Excellence in Infectious Diseases
Texas Tech University Health Sciences Center
5001 El Paso Drive, El Paso TX, Zip Code 79905
1. MicroRNA biogenesis
miRNAs are a class of small RNAs around 22 nucleotides long that have emerged as critical regulators modulating almost all biological processes involving gene expression. MicroRNA genes are transcribed as long primary microRNAs (pri-miRNAs) and then processed by the Drosha–DGCR8 (DiGeorge syndrome critical region gene 8) complex into ~60-nt pre-miRNAs, which is the key step in miRNA biogenesis. How exactly the Drosha–DGCR8 complex recognizes pri-miRNAs and selects the processing site is not well understood. We have developed a new approach that we are currently using to study how the Drosha–DGCR8 complex chooses the processing site in human cells. Our previous studies suggested that the sequence of a given miRNA is not fixed, as annotated in the miRBase, but shows considerable variation at the ends. We are also assessing the functional significance of variant miRNA forms and the mechanism of their generation.
Taking advantage of our knowledge of miRNA biogenesis, which is the basis for how exogenously introduced siRNA/shRNA can work in mammalian cells, we are also interested in improving the design of siRNA/shRNA to increase potency and reduce side effects.
2. CRISPR-Cas9 system-based genome-wide functional screening in human cells
Taking advantage of the ease of knocking out target genes using the newly developed CRISPR-Cas9 genome-editing tool, we have independently developed an approach based on this system to perform genome-wide knockout screening in human cells. Currently we are using the method to study various biological processes, including virus replication.
Major Invited Speaker/Meeting Participant
2014 The Lower and Upper Stem–ssRNA Junctions Together Determine the Drosha Cleavage Site. RNA silencing—Keystone symposia (01/31/2014-02/05/2014), Seattle, US.
2014 Genome-Wide Functional Screening with the CRISPR-Cas9 System in Human Cells. GTC-None-coding RNAs and RNAi. (06/19/2014-06/20/2014), San Diego, USA.
2015 A CRISPR-Cas9-Based Screen for Human Genes Essential for West Nile Virus-Induced Cell Death. Precision genome engineering and synthetic biology—Keystone symposia (01/11/2015-01/16/2015), Big Sky, USA.
B.S., Fudan University, Shanghai, China (1989-1993)
M.S., Fudan University, Shanghai, China (1993-1997)
Ph.D., Fudan University, Shanghai, China (1997-2000)
Postdoctoral training, UCLA (2003-2005) and the Immune Disease Institute, Harvard Medical School (2005-2008)
Selected Recent publications
Jang-Gi Choi, Preeti Bharaj, Sojan Abraham, Hongming Ma, Guohua Yi, Chunting Ye, Ying Dang, N. Manjunath, Haoquan Wu*, Premlata Shankar. Multiplexing 7 miRNA-based shRNAs to suppress HIV replication. Molecular Therapy. 2014 Oct 31. doi: 10.1038/mt.2014.205. *Co-corresponding author.
Hongming Ma, Junli Zhang and Haoquan Wu*. Designing Ago2-specific siRNA/shRNA to avoid competition with endogenous miRNAs. Molecular Therapy-Nucleic Acids. In press. *Corresponding author.
Hongming Ma, Yonggan Wu, Ying Dang, Jang-Gi Choi, Junli Zhang and Haoquan Wu*. Pol III Promoters to Express Small RNAs: Delineation of Transcription Initiation. Molecular Therapy - Nucleic Acids. 2014 May, 3: e161; doi:10.1038/mtna.2014.12. *Corresponding author.
Hongming Ma, Yonggan Wu, Jiang-Gi Choi, Haoquan Wu*. The Lower and Upper stem-ssRNA Junctions Together Determine the Drosha Cleavage Site. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20687-92. doi: 10.1073/pnas.1311639110. Epub 2013 Dec 2. *Corresponding author.
Chunting Ye, Jiang-Gi Choi, Sojan Abraham, Haoquan Wu, Diaz D, Terreros D, Premlata Shankar, Manjunath N. Human macrophage and dendritic cell-specific silencing of high-mobility group protein B1 ameliorates sepsis in a humanized mouse model. Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21052-7. doi: 10.1073/pnas.1216195109. Epub 2012 Dec 3.
Haoquan Wu*, Hongming Ma, Chunting Ye, Danielle Ramirez, Shuiping Chen, Jessica Montoya, Premlata Shankar, Xiaozhong Wang, Manjunath N. Improved siRNA/shRNA functionality by mismatched duplex. PLoS One. 2011;6(12):e28580. doi: 10.1371/journal.pone.0028580. Epub 2011 Dec 9. *Co-corresponding author.
Chunting Ye, Sojan Abraham, Haoquan Wu, Premlata Shankar, Manjunath N. Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis. PLoS One. 2011 Mar 15;6(3):e17889. doi: 10.1371/journal.pone.0017889.
Haoquan Wu*, Joel R. Neilson, N. Manjunath. microRNA cloning from cells of the immune system. Methods Mol Biol. 2010;667:67-77. doi: 10.1007/978-1-60761-811-9_5. *Corresponding author.
Haoquan Wu*, Chunting Ye, Danielle Ramirez, N. Manjunath. Alternative Processing of Primary microRNA Transcripts by Drosha Generates 5' End Variation of Mature microRNA. PLoS ONE 2009, 4(10): e7566. doi:10.1371/journal.pone.0007566. *Co-corresponding author.
N. Manjunath,Haoquan Wu, Premlata Shankar. Lentiviral delivery of short hairpin RNAs. Adv Drug Deliv Rev. 2009 Jul 25;61(9):732-45. Epub 2009 Mar 31.
Priti Kumar, Hong-Seok Ban, Sang-Soo Kim,Haoquan Wu, Todd Pearson, Dale Greiner, Amale Laouar, Jiahong Yao, Viraga Haridas, Katsuyoshi Habiro, Yong-Guang Yang, et al, T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice. Cell. 2008 Aug 22;134(4):577-86. Epub 2008 Aug 7.
Haoquan Wu, Joel R. Neilson, Priti Kumar, Monika Manocha, Premlata Shankar, Phillip A. Sharp, N. Manjunath. miRNA Profiling of Naive, Effector and Memory CD8 T Cells. PLoS ONE. 2007 Oct 10;2(10):e1020.
Priti Kumar,Haoquan Wu, Jodi L. McBride, Kyeong-Eun Jung, Moon Hee Kim, Beverly L. Davidson, Sang Kyung Lee, Premlata Shankar & N. Manjunath. Transvascular delivery of small interfering RNA to the central nervous system. Nature. 2007 Jul 5; 448(7149):39-43. Epub 2007 Jun 17.
Ying Dang, Ph.D.
Post Doctoral Research Associate
Hongming Ma, Ph.D.
Post Doctoral Research Associate
Medical Research Technician II