Dr. Fernando Ontiveros
Title: Assistant Professor
Office: Skalny 215
Phone: (585) 899-3881
Education: Ph.D., M.S., University of Rochester
B.S., National Autonomous University of Mexico
Targeted delivery of biomolecules to specific tissues provides biologists with an opportunity to develop improved approaches to treat and prevent disease. I am interested in a multidisciplinary approach that makes use of concepts and tools from the fields of chemistry, material science, cell biology and immunology. Research in my laboratory focuses on the use of lipid-based nanoparticles to understand the molecular basis of inflammation and to explore novel ways in which drug delivery and vaccination can become more effective. Trained as an immunologist, I conducted postdoctoral research in the fields of inflammation and antimicrobials before joining the faculty at SJFC. My time is divided between teaching Microbiology & Immunology to Biology and Nursing majors and establishing a Nanobiology Lab at Fisher.
- BIO 107 Microbes and Disease
- BIO 214 Microbiology
- BIO 418 Immunology
Inflammation and immune cell activation Targeted nanoparticles in therapeutics and vaccination
At the Lab we work on two closely related projects:
The first project is to produce lipid-based nanoparticles that will specifically target eukaryotic cells to deliver a cargo consisting of small interfering RNA (siRNA). Immunotargeted nanoparticles (ITNPs) are a recently developed molecule-delivery system. They consist of stabilized unilamellar vesicles with a diameter of approximately 100nm. Monoclonal antibodies raised against cell surface molecules are covalently bound to the surface of the particle, which can be loaded with a variety of molecules. In the past, we successfully produced ITNPs that delivered fluorochrome-labeled small RNAs to human neutrophils. We will use a similar approach to silence the inflammasome, a cytoplasmic macromolecular complex involved in the immune response induced in pathologies like atherosclerosis and gout:
- Produce and characterize ITNPs loaded with small RNAs.
- Identify macrophage surface molecules that will enhance the uptake of ITNPs.
- Use an array of siRNAs that will effectively inhibit the activity of the NALP3 inflammasome.
This project will involve students in basic research with the potential to produce real advances in the field. With an aging population in the developed world, the treatment of inflammatory disorders will remain relevant for years to come. Furthermore, the project can be expanded to address two clear alternative avenues for the use of ITPNs: drug delivery to cancer cells and vaccination. The ability of ITNPs to deliver both vaccine preparations to leukocytes or deliver oncology drugs to cancer cell lines can be tested in our lab.
The second project will test the ability of endogenous compounds to induce activation of cells of the immune system. The benefits of this research are two fold: a) it will expand our understanding of inflammation-based pathologies and b) it will characterize the cellular immune response elicited by molecules with the potential to be used as enhancers of immunity against infection. This is an area of study in which there is still much to be learned, as the effect of endogenous organic crystals on the immune system has only been recognized recently. My previous work with uric acid will serve as a starting point for this project. Both uric acid and cholesterol crystals free of any microbial product are capable of inducing inflammation. Uric acid is a breakdown product of nucleic acids found in large quantities in human plasma, where it can function as an antioxidant. Monosodium uric acid (MSU) crystals have been characterized as an endogenous danger signal produced upon cell death, alerting the immune system to injury caused by either trauma or infection. Research conducted previously indicates that MSU (and more recently, cholesterol crystals) can stimulate acute innate immune responses in vitro and in vivo. In this project, we will:
- Identify organic molecules with the potential to stimulate inflammatory responses.
- Study the cellular events that follow exposure to selected organic molecules.
- Characterize the cellular immune response.
Students will be part of a multidisciplinary effort to better understand sterile inflammation and perhaps use this knowledge to design new ways to fight disease. In addition to performing experiments in the areas of organic chemistry, cell biology and immunology, the students will be exposed to concepts in pathology and vaccine design. The realization that organic crystals generated within the body can cause inflammation is not a recent event. It has been only in the last 5 years, however, that the cellular basis for this phenomenon has started to become clear. Using in vitro techniques we will ask how organic compounds activate cells of the immune system and will search for new molecules that could be used to mimic these effects. The benefits of this research are two fold: On one hand, we will gain a better understanding on how the in vivo accumulation of organic crystals induces inflammation and, on the other hand, we will acquire information on the kind of immune response that would be generated if these compounds were used as part of a vaccine formulation.
ANTIMICROBIAL ACTION OF CATIONIC AMYLOID FIBRILS FOUND IN HUMAN SEMEN
Fernando Ontiveros, David Easterhoff, Lauren R Brooks, Brittany Ross, Joanna S. Olsen, Changyong Feng, Dwight J. Hardy, Paul M. Dunman, Stephen Dewhurst. (Submitted)
TRANSIENT HYPERCAPNIA REVEALS AND UNDERLYING CEREBROVASCULAR PATHOLOGY IN A MURINE MODEL FOR HIV-1 ASSOCIATED NEUROINFLAMMATION: ROLE OF NO-cGMP SIGNALING AND NORMALIZATION BY INHIBITION OF PHOSPHODIESTERASE-5
Jharon Silva, Oksana Polesskaya, Walter Knight, Johnny Ting Zheng, Megan Granger, Fernando Ontiveros, Changyong Feng, Chen Yan, Karl Kasischke, Stephen Dewhurst. (Submitted)
IL-1 GENERATED SUBSEQUENT TO RADIATION-INDUCED TISSUE INJURY CONTRIBUTES TO THE PATHOGENESIS OF RADIODERMATITIS
Matthew Janko, Fernando Ontiveros, Thomas J. Fitzgerald, A. Deng, Maria DeCicco and Kenneth L. Rock. Rad Res. 2012 Aug 1
TYPE-I IFN SUPPORTS PRIMARY CD8+ T CELL RESPONSES TO PEPTIDE-PULSED DENDRITIC CELLS IN THE ABSENCE OF CD4+ T CELL HELP
Fernando Ontiveros, Elizabeth B. Wilson and Alexandra M. Livingstone. Immunology. 2011 Apr; 132 (4):549-58
THE STERILE INFLAMMATORY RESPONSE
Kenneth L. Rock, Eicke Latz, Fernando Ontiveros and Hajime Kono. Annu Rev Immunol. 2010 Mar; 28:321-42
URIC ACID PROMOTES AN ACUTE INFLAMMATORY RESPONSE TO STERILE CELL DEATH IN MICE
Hajime Kono, Chun-Jen Chen, Fernando Ontiveros and Kenneth L. Rock. J Clin Invest. 2010 Jun 1;120(6):1939-49
UNRAVELLING THE MECHANISMS OF HELP FOR CD8 T CELL RESPONSES
Alexandra Livingstone, Elizabeth B. Wilson, Fernando Ontiveros, Jyh-Chiang Wang. Immunol Res. 2009 Feb; 45:209-17
THE INFLUENCE OF INNATE IMMUNE MECHANISMS ON CD4 AND CD8 T CELL RESPONSES
Fernando Ontiveros; Advisor: Alexandra Livingstone. Doctoral Thesis, U of Rochester, 2008
ACTIVATION OF MURINE DENDRITIC CELLS BY THREE PROTECTIVE EPITOPES AGAINST CYSTYCERCOSIS (spanish)
Fernando Ontiveros; Advisor: Edda Sciutto. Undergraduate Thesis, UNAM School of Sciences, 2001
THE NUCLEAR MATRIX CONCEPT
Fernando Ontiveros; Berkeley Scientific, Spring 2001
SCIENCE BOOKLET: BIOLOGY OF THE CELL NUCLEUS (spanish)
Olga Echeverria & Fernando Ontiveros (editors); National Autonomous University of Mexico, 2001
EMERGING VIRUSES: FICTION OR REALITY (spanish)
Fernando Ontiveros; Ciencias, No. 51, 1998