“I really am stoked on learning about the basic fabric of our existence ... the complexity is mind-boggling.”
For more than a decade, Kevin Morris, Ph.D. has been one of the brightest lights in RNA research.
Morris was the first to recognize unique properties of non-coding RNA; he is considered an international leader in the field.
The goal of his work, in his words, is “to understand the role of non-coding RNA in life, evolution and selection.” and to use that knowledge to develop novel therapies for AIDS, cancer and other diseases.
At the Center for Gene Therapy, Morris will focus on manipulating RNA in a variety of ways to control and repress HIV-1.
Morris has led research laboratories at the renowned Scripps Research Institute in La Jolla, California as well as the University of New South Wales, Australia. His relationship with City of Hope began in 2004 with researcher and adjunct professor positions at the Beckman Research Institute of City of Hope.
The goal of this project is to develop two approaches to controlling HIV-1; a gp120 targeted aptamer fused small RNAs that transcriptionally silence HIV and conditionally replicating vectors that stably repress and/or excise HIV and spread this repression to viral infected cells. We will develop both these approaches and test their relative efficacy in human cell and in vivo mouse systems. I have expertise in RNA targeted regulation of gene expression and my lab has carried out most of the mechanistic studies to determine how non-coding RNAs modulate gene transcription at the transcriptional level.
I also have extensive experience in conditionally replicating lentiviral vectors and the development of small non-coding RNAs capable of transcriptionally silencing or activating HIV-1. I have a demonstrated track record of success with regards to RNA-mediated modes of epigenetic regulation of HIV, aptamer and lentiviral vector development and an ability to build teams of investigators when disparate expertise is required. Overall, my experiences and successes with previously funded applications have prepared me well to lead this project.
Contributions to Science
(1) I am credited for being the first person to show that non-coding RNAs can control gene transcription by guiding epigenetic silencing complexes to target loci in human cells (PMID:15297624). My lab was also the first to show that long antisense non-coding RNAs (lncRNAs) function endogenously to control gene transcription (PMID: 19008947) and that this mechanism of action involves DNMT3a, HDAC-1 and EZH2 (PMID: 16397511) and promoter-associated RNAs as targets (PMID: 17640892). Notably PMID: 17640892 was the first observation that gene promoters are transcribed, changing our collective understanding of transcription in human cells. I am now recognized as an international leader in the non-coding RNA field (PMID:24776770). Notable there are now over 4,600 papers on the subject of lncRNAs.
(2) The Morris lab was the first to show that pseudogenes are functional regulatory entities in humans controlling the transcription and translation of their protein-coding gene counterpart (PMID 23435381 and PMID: 21151833). We also observed that HIV functionally controls latency using a mechanism of action similar to pseudogenes and antisense lncRNAs (NIHMSID#569381).
(3) The Morris lab has pioneered the development of conditionally replicating lentiviral vectors (PMID: 19066594) for targeted regulation of HIV using non-coding RNAs (PMID:22122263) and CRISPR/Cas gene editing technologies (PMID: 24787973).
Ongoing projects in the Morris lab include: mechanistic determination of small and long ncRNA mediated transcriptional gene silencing (TGS) and epigenetic gene regulation in human cells; transcriptional gene silencing (TGS) of HIV-1 and several oncogenes involved in human cell cancers; transcriptional gene activation (TGA) /de-repression; whereby we utilize ncRNAs, antisense oligonucleotides or zinc-finger activator conjugates targeted to endogenous regulatory long ncRNAs; and nucleic acid based genetic therapy targeted approaches to delivering regulatory ncRNAs or gene specific zinc-finger activator/repressors to cells to treat different diseases. Current methods involve developing receptor targeted aptamers and mobilization competent lentiviral vectors to parasitize HIV-1.
Visit the Morris Lab for more information.
Morris K.V., S. W-L. Chan, S.E. Jacobsen, D.J. Looney. Small interfering RNA-induced transcriptional silencing in human cells. Science, 2004, Vol. 305, 1289-1292. PMID: 15297624.
Morris K.V., Santoso S, Turner AM, Pastori C, Hawkins PG. Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 2008 Nov;4(11):e1000258. PMID: 19008947/PMCID: 2576438.
Weinberg, M.S., L.M. Villeneuve, A. Ehsani, L. Aagaard, Z. Chen, A.D. Riggs, J.J. Rossi and K.V. Morris. The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells. RNA. 2006, Vol. 12, 256-262. PMID: 16397511.
Han J, D. Kim, and K.V. Morris Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells. PNAS, 2007 July 24(104):30. PMID: 17640892/PMCID: 1924466.
K.V. Morris and J. S. Mattick. The Rise of Regulatory RNA. Nature Reviews Genetics 2014 Apr 29. doi: 10.1038/nrg3722. PMID:24776770.
Turner AM, De La Cruz J, Morris K.V., Mobilization-competent Lentiviral Vector-mediated Sustained Transcriptional Modulation of HIV-1 Expression. Mol Ther. 2008 Dec 9;. PMID: 19066594
Weinberg MS, Morris KV. A New World Order: Tailored Gene Targeting and Regulation Using CRISPR. Molecular Therapy. 2014 May;22(5):893. PMID: 24787973
Turner AM, Ackley AM, Matrone MA, Morris KV. Characterization of an HIV-targeted transcriptional gene-silencing RNA in primary cells. Hum Gene Ther. 2012 May;23(5):473-83. PMID:22122263
For a complete List of Published Work see my bibliography: