Michael J Heller

University of California San Diego, USA

Title: Protease Biomarkers for Cancer Liquid Biopsy and Companion Diagnostics

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Biography

Michael J. Heller received his PhD in Biochemistry from Colorado State University in 1973. He was an NIH Postdoctoral Fellow at Northwestern University from 1973 to 1976. From 1976 to 1984 he was supervisor of the DNA Technology Group at Amoco Corporation (Standard Oil Indiana) During that time he carried out early bioengineering and recombinant DNA work on plants, algae and photosynthetic bacteria for energy and chemical production, and developed some of the first fluorescent resonant energy transfer (FRET) and chemiluminescent oligonucleotide probes for DNA hybridization analysis. He also oversaw Amoco’s sponsored energy and chemical research work at Cetus Corporation, which included the cloning of thermophilic enzymes. Dr. Heller was the Director of Molecular Biology at Molecular Biosystems, Inc., from 1984 to 1987. He was a co-founder of Integrated DNA Technologies, and served as President and Chief Operating Officer from 1987 to 1989. He was a co-founder of Nanogen, and served as the Chief Technical Officer from 1993 to 2001. Nanogen carried out the successful development and commercialization of electronic DNA microarray technology for clinical diagnostic genotyping applications. He was also a Distinguished Scientist at the OHSU Knight Cancer, Center for Cancer Early Detection and Research (CEDAR), in Portland from 2017-2021, Oregon. Dr. Heller is Professor (Emeritus/Recall) in the Departments Bioengineering and Nanoengineering at the University California San Diego (2000-Present). He has also co-founded Biological Dynamics (La Jolla, CA) a company which is developing new sample to answer cancer diagnostics technology, based on the novel dielectrophoretic (DEP) technology developed at his UCSD lab. Dr. Heller has extensive industrial experience in biotechnology, biomedical and molecular diagnostic devices and nanotechnology, with particular expertise in the areas of DNA probe diagnostics, protease biomarker detection, electrokinetic lab-on-a-chip devices, FRET/fluorescent detection technologies and electric field assisted self-assembly of DNA nanostructures. Dr. Heller has over 100 publications and 60 issued US patents.

Abstract

Proteases represent a large class of enzymes that have been associated with a wide range of diseases that include: cancer, cardiovascular diseases; coagulation disorders; inflammatory diseases, diabetes, sepsis and infectious diseases. While proteases have some limited use in disease diagnostics, their full potential has not been exploited. Protease are not only biomarkers, but also active agents that can lead to other pathology and patient morbidity. In most cases, the detection of proteases is carried out using immunofluorescent assay techniques. However, because they are catalyst which rapidly convert specific protein and peptide substrates into products, they offer an added advantage for signal amplification. We have capitalized on this property and developed rapid sample to answer protease assays based on fluorescent charge-changing peptide substrates. These assays can be carried our using very small volumes (5ul-10ul) of whole blood, plasma or serum samples. No sample preparation is required and the fluorescent peptide products can be detected in about 30 minutes using simple mini-gel electrophoretic formats. In the case of pancreatic cancer (PDAC) we have detected elevated levels of digestive enzymes trypsin, chymotrypsin and elastase, as well as matrix metalloproteinases (MMP-2, 9) and Cathepsins in numerous patient samples. Our more recent work is directed at also developing companion diagnostics for protease inhibitor therapeutics.