John Rossi, Ph.D., the Lidow Family Research Chair and professor and chair of the Department of Molecular and Cellular Biology, is widely regarded as a world leader in the development of RNA interference and in clinical research involving nucleic acids for the treatment of various diseases. Currently, he is focusing on enhancing the intracellular efficacy of ribozymes, small RNAs and siRNAi, and their application to gene therapy for HIV and cancer.
In 2019, he received the 2019 Outstanding Achievement Award presented by the American Society of Gene and Cell Therapy (ASGCT). The award is presented annually to the ASGCT member who has achieved pioneering research success and a lifetime of significant contributions to the field of gene and cell therapy. It is the society’s highest honor.
Dr. Rossi is the editor in chief of Molecular Therapy-Nucleic Acids and deputy editor of Molecular Therapy. He has authored more than 275 peer-reviewed papers and more than 70 book chapters. He is also founding president of Oligonucleotide Therapeutics Society.
Dr. Rossi joined City of Hope in 1980 after receiving his Ph.D. in microbial and eukaryotic genetics at the University of Connecticut.
1976, University of Connecticut, Ph.D., Microbial Genetics
1971, University of Connecticut, M.S., Microbial Genetics
1969, University of New Hampshire, B.A., Biology
1976 - 1979, Brown University, Providence, RI, Postdoc, Biology and Medicine
2019-present, Dean Emeritus, Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, Center for RNA Biology and Therapeutics
2014 - 2016, Associate Director for Education and Training, City of Hope Comprehensive Cancer Center, Duarte, CA
2001 - present, Professor and Director, Center for RNA Biology and Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA
2001 - present, Adjunct Professor, Division of Biomedical Sciences, University of California Riverside, Riverside, CA
2001 - present, Co-leader, Cancer Biology Program, Beckman Research Institute of City of Hope, Duarte, CA
2001 - present, Associate Chair, Shared Resources Advisory Committee, City of Hope Comprehensive Cancer Center, Duarte CA
2001 - 2016, Associate Director for Basic Research, City of Hope Comprehensive Cancer Center, Duarte, CA
1988 - 2019, Dean, Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA
1996 - present, Adjunct Professor, Department of Biochemistry and Microbiology, Loma Linda University, CA
1994 - present, Adjunct Professor, Department of Biology and Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
1996 - 2001, Director, Department of Molecular Biology, Section Head, Gene Regulation, Beckman Research Institute of City of Hope, Duarte, CA
1996, Director, Center for Molecular Biology and Gene Therapy, Loma Linda University, CA
1994 - 1996, Associate Director, Center for Molecular Biology and Gene Therapy, Loma Linda University, CA
1992 - 1994, Chair, Department of Biology, Beckman Research Institute of City of Hope, Duarte, CA
1990 - 1994, Director, Department of Molecular Genetics, Beckman Research Institute of City of Hope, Duarte, CA
1990 - 1994, Research Scientist, Department of Molecular Genetics, Beckman Research Institute of City of Hope, Duarte, CA
1988 - 1992, Associate Chair, Department of Biology, Beckman Research Institute of City of Hope, Duarte, CA
1984 - 1989, Associate Research Scientist, Department of Molecular Genetics, Beckman Research Institute of City of Hope, Duarte, CA
1980 - 1984, Assistant Research Scientist, Department of Molecular Genetics, Beckman Research Institute of City of Hope, Duarte, CA
The Biology and Applications of Small RNAs
The Rossi Lab has as its primary focus studies on the functions and therapeutic applications of small RNAs. Within the past two decades there has been an explosion of new findings about roles that small RNAs play in biological processes. Ribozymes are RNA molecules with enzymatic activities. There are many different types of ribozymes in nature but our lab has focused upon the hammerhead motif which is found as part of the self-cleaving domain of small plant viruses. We have exploited these ribozymes for both basic studies of RNA catalysis and for therapeutic applications. Ribozymes developed in our research program have been developed to target HIV and these have been inserted into human blood progenitor cells via a retroviral vector as part of a gene therapy program for the treatment of HIV infection. To date 10 HIV positive patients have been treated with ribozymes developed in the lab. Efforts to improve catalytic efficiency and co-localization of ribozymes with their targets in mammalian cells are still an ongoing effort in the lab.
The recent discovery of RNA interference in which long double stranded RNAs or RNA hairpins are processed in smaller 21 to 23 base duplexes called small interfering RNAs and micro RNAs has revolutionized mammalian cell genetics. These small RNAs can be used to inhibit gene expression by targeting mRNAs with complementary sequences. The lab has been studying the mechanism of RNAi at the biochemical level, as well as exploiting this phenomenon for therapeutic applications in AIDS and cancer. One of our discoveries is that dsRNAs that are long enough to be processed by the RNAi machinery, but short enough not to activate the interferon pathway, called Dicer substrate siRNAs, have enhanced potency and duration of action relative to the 21 base long siRNAs used in most studies. One focus of the laboratory is to understand how linking processing with function enhances the activity of these siRNAs. Another area of research in the lab concerns the mechanisms by which small double stranded RNAs can trigger transcriptional gene silencing and activation by modulating the histone code. These small RNAs use components of the RNA interference machinery to target chromatin. A major effort in the lab is to elucidate the active components of this process and to apply transcriptional gene silencing in a therapeutic setting. Finally, the laboratory has been actively using an in vitro evolution process (SELEX) to evolve RNA aptamers for use as therapeutics, but also to serve as siRNA delivery vehicles. We have successfully evolved families of aptamers targeting the HIV envelope that neutralize HIV infectivity, yet can be internalized in HIV infected cells to deliver therapeutic siRNAs. Aptamers are also being selected against specific cellular receptors for use in cancer therapy.
2019, Outstanding Achievement Award, American Society of Gene & Cell Therapy
2013, Special Recognition Award, American Society of Gene and Cell Therapy
2008, Cozzarelli Award, National Academy of Sciences 2011 Elected as AAAS Fellow in Medical Sciences
2002, Merit Award, Division of AIDS, National Institute of Allergy and Infectious Diseases
1993, Gallery of Scientific and Medical Achievement, City of Hope
1991, American Association for Clinical Chemistry Outstanding Speaker Award
1990, Walter MacPherson Society Research Award, Loma Linda Univ. School of Medicine
Reebye V, Saetrom P, Mintz PJ, Huang K-W, Swiderski P, Peng L, Liu C, Liu X, Lindkaer-Jensen S, Zacharoulis D, Kostomitsopoulos N, Kasahara N, Nicholls JP, Jiao LR, Pai M, Spalding DR, Mizandari M, Chikovain T, Emara MM, Haoudi A, Tomalia DA, Rossi JJ, Habib NA. (2014) A Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo. Hepatology 59(1): 216-227. PMCID: PMC4655108
Voutila J, Reebye V, Roberts RC, Protopapa P, Andrikakou P, Balkey DC, Habib R, Huber H, Saetrom P, Rossi JJ, Habib N. (2017) Development and mechanism of small activating RNA targeting CEBPA, a novel therapeutic in clinical trials for liver cancer. Mol. Ther., 25(12): 2705-2714. PMCID: PMC5768526