 |
 |
Lance A. Liotta, Ph.D. Co-Director/Professor, Center Proteomics and Molecular Medicine George Mason University, Applied Proteomics and Molecular Medicine, Institute Advance Biomedical Research Research Hall, Room 163 September 6, 2018 12:00 pm - 1:00 pm Topic: Novel Affinity Chemistries Coupled with Nanotechnology: Application to Personalized Medicine Abstract: Many low abundance biomarkers and exosomes for early detection of cancer and infectious diseases in tissues and body fluids are invisible to mass spectrometry and immunoassays because they exist in very low concentrations, are masked by high abundance proteins such as albumin and immunoglobulins, and are very labile. Exosome biomarkers are needed that can authenticate the cell of origin (e.g. tumor cell vs normal cell) for exosomes purified from a body fluid. To overcome these barriers, we created (under NIH funding) novel porous buoyant core-shell hydrogel nanoparticles (Nanotrapstm) containing novel reactive chemical baits for protein and peptide harvesting, concentration and preservation in body fluids. Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles were functionalized with amino containing dyes via zero length crosslinking amidation reactions. Nanoparticles functionalized in the core with >20 different molecular baits showed preferential high affinities (KD <10-11 M) for exosomes and low abundance protein analytes. Used in body fluids as a one step, in-solution, preprocessing step, the nanoparticles captured exosomes, viruses, and low abundance proteins and peptides and nucleic acids, excluding albumin and other unwanted proteins; this achieved a 10,000 fold amplification of the sensitivity of mass spectrometry (MS) enabling the discovery of candidate cancer and infectious disease biomarkers that were previously undetectable. The nanoparticles can be preloaded with specific cytokines or exosomes, and injected subcutaneously. From the injection site the loaded nanoparticles travel to the local draining sentinel lymph node to induce massive remodeling of the immune cell subpopulations. The unique properties of the chemical affinity dyes permitted us to create another new analytical technology Protein Painting. Protein Painting enables the direct sequencing of protein-protein contact points within interacting protein complexes, and networks: supporting the discovery of novel therapies or antibodies that block pathogenic protein interactions. Biography: Dr. Liotta received the MD (Board Certified) and PhD (Bioengineering) from Case Western Reserve University, and fulfilled his residency at the National Institutes of Health (NIH), where he initiated a research program that, to date, has yielded more than 700 publications (Highly Cited Investigator), and more than 100 issued or allowed patents. For his PhD in Biomedical Engineering (MD/PhD Case Western Reserve), he developed the first mathematical model of the cancer metastatic process and studied the early release of circulating tumor cells and tumor cell clumps. At the NIH he went on to investigate the process of tumor invasion and metastasis at the molecular level (MMP2, and TIMP2). He was the first to describe tumor cell invasion of the basement membrane (3-step hypothesis) and the role of tumor cell pseudopodia in tumor cell invasion. At NIH Dr. Liotta was Chief, Laboratory of Pathology, Chief, Section of Tumor Invasion and Metastasis, and Deputy Director of NIH under NIH Director Bernadine Healy (Human Genome Program). He and Dr. Emanuel Petricoin of the FDA set up the first NIH/FDA Clinical Proteomics Program. In 2005 Mason recruited Dr. Liotta, and Dr. Petricoin (co-Directors), and their distinguished scientific team, to create the Center for Applied Proteomics and Molecular Medicine (CAPMM). The Mission of CAPMM is to discover disease mechanisms, invent new technologies, educate the scientists of the future, and translate knowledge to help patients through prevention, early detection, and treatment. Dr. Liotta has invented and patented, along with his laboratory co-inventors, high-impact technologies in the fields of diagnostics; microdissection (Laser Capture Microdissection in the Smithsonian Collection), and proteomics (Reverse Phase Protein Microarrays, Biomarker Harvesting Nanoparticles, Preservation chemistries tissue, and Protein Painting to discover drug targets), that have been used to make broad discoveries. The Laser Capture Microdissection prototype is in the Smithsonian Collection. The CAPMM team applies these technologies, for example, to markers for early stage disease, accurate diagnosis of Tuberculosis and Lyme disease (Dr. Alessandra Luchini), individualized therapy for primary and metastatic cancer (Dr. Mariaelena Pierobon, Dr. Julia Wulfkuhle), therapy of premalignant breast cancer as a strategy for prevention (Dr. Virginia Espina), and an accredited CAP/CLIA diagnostic lab for patient testing. Dr. Liotta has received numerous scientific awards, including election to AIBME Fellows status, the Arthur S. Flemming Award, the NIH Award of Merit, the Surgeon General's Medallion, and the 2015 Virginia SHEV award for Research and Scholarship. Dr. Liotta has been PI on 10 NIH grants, 3 DOD Cancer Program awards, a Komen Breast Cancer Foundation award, the Walker Foundation award, the US-Italy bilateral agreement award, Virginia Commonwealth, and Co-PI on more than 16 other grants with Dr. Petricoin, totaling more than $20M in funding. CAPMM (Amy Adams, Dr. Andrea Cobb) founded the Aspiring Scientists Summer Internship Program and the Galileo Science Café to promote science for the community and to inspire the next generation of scientists. CAPMM inventions licensed by Mason are the basis of two startup biotech companies Ceres Nanoscience and Theranostics/Avant DX. Two additional startups are being formed using IP licensed from CAPMM.