Engineering Synthetic Biomarkers for Multiplexed Urinary Monitoring of Disease
Gabriel Kwong, Ph.D.
Burroughs Wellcome Fund CASI Fellow, Massachusetts Institute of Technology
Biomarkers are increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous biomolecules. Here I describe the development of “synthetic biomarkers” comprising protease-sensitive nanoparticles that perform three functions following administration: they target sites of disease, sense dysregulated protease activities, and release reporters into the host urine as indicators of disease. These urinary reporters are mass-encoded to allow multiplexed analysis by mass spectrometry, or functionalized with capture ligands to allow detection by low-cost paper tests in global health settings. By engineering nanoparticles to sense different proteases, I show that synthetic biomarkers may be used to noninvasively monitor liver fibrosis and reversal, detect dangerous pulmonary blood clots and detect cancer earlier compared to blood biomarkers. Synthetic biomarkers have the potential to significantly expand our repertoire of diagnostic nanomedicines, and may allow systems-level analysis of multi-enzymatic networks in health and disease.
Dr. Kwong is the Burroughs Wellcome Fund CASI Fellow at MIT in the laboratory of Dr. Sangeeta N. Bhatia. He earned his B.S. in Bioengineering with Highest Honors from University of California at Berkeley, and his Ph.D. from Caltech under the guidance of Dr. James R. Heath. His work has been published in leading scientific journals such as Nature Biotechnology and Nature Medicine, and profiled broadly including coverage in The Economist, Huffington Post and WGBH-2, Boston’s PBS station. Dr. Kwong has received multiple honors including the NIH Ruth L. Kirschstein National Research Service Award, named a “Future Leader in Cancer Research and Translation Medicine” by the Massachusetts General Hospital in 2012, and awarded the Burroughs Wellcome Fund Career Award at the Scientific Interface in 2013 – a distinction given to the 10 most innovative cross-disciplinary investigators in the nation. He has directly mentored 8 undergraduate and graduate trainees, and holds 7 issued or pending patents in cancer nanotechnology.