• Cell-free nucleic acids
• Non-invasive prenatal testing (NIPT)
• Liquid biopsy for cancer diagnostics

Dennis Lo’s research focuses on elucidating the biology of circulating DNA in both health and disease. His team investigates the molecular characteristics of circulating DNA, including epigenetic modifications and fragmentomic patterns, to understand the mechanisms underlying its generation and clearance. By integrating these biological insights with advanced analytical technologies, his research aims to enhance the diagnostic performance of circulating DNA analysis and drive its clinical translation for early detection, monitoring, and precision management of human diseases.

The research team led by Dennis Lo has been at the forefront of cell-free nucleic acids research, pioneering groundbreaking discoveries and driving significant advancements in the field. One of the team’s seminal achievements was the discovery of cell-free fetal DNA in maternal circulation in 1997. This groundbreaking finding revolutionised the research landscape and opened up new possibilities for noninvasive prenatal diagnosis, now widely known as noninvasive prenatal testing (NIPT). This innovation has led to a paradigm shift, replacing invasive methods of prenatal diagnosis and becoming the standard practice for screening Down syndrome, as endorsed by international medical societies and professional bodies. NIPT is now used in many countries around the world, with about 10 million tests performed every year.

Beyond prenatal care, Dennis has pioneered numerous innovations in the use of circulating nucleic acids for cancer detection, establishing several foundational approaches in cancer liquid biopsy. Notably, his team developed genome-wide methylation analysis of cell-free DNA for multi-cancer early detection (MCED). This approach offers the distinct advantage of identifying the tissue of origin of circulating DNA, enabling the simultaneous detection of multiple cancer types and holding transformative potential for early cancer diagnosis. This technology was subsequently licensed to Grail to facilitate its clinical translation, leading to the launch of the first commercially available MCED test, Galleri, which was recognised as one of TIME Magazine’s “Best Inventions of 2022.”

Recent work from Dennis’s team has contributed to the emergence of an exciting new research field centred on cell-free DNA known as ‘fragmentomics’. A key insight was the recognition that cell-free DNA exhibits nonrandom fragmentation patterns, leading to deeper investigation into the biology of DNA fragmentation. Building on this concept, the team have developed a range of fragmentomics-based markers with important diagnostic applications for cancer detection and tissue-of-origin analysis. Notably, the team pioneered a novel approach, termed as FRAGmentomics-based Methylation Analysis (FRAGMA), which enables methylation inference and tissue deconvolution directly from cell-free DNA fragmentation patterns. The potential of this approach has been demonstrated in cancer settings, including the differentiation of patients with and without cancer of various types. This forms the basis for the development of a second-generation multi-cancer early detection (MCED) test. Collectively, these advances represent a pioneering framework for cell-free DNA analysis, opening new avenues for both fundamental research and clinical translation.

1. AACR-Irving Weinstein Foundation Distinguished Lectureship, The American Association for Cancer Research (AACR) (2026)
2. Richard B. Johnston, Jr., MD Prize, March of Dimes (2025)
3. LV Jiménez Díaz Commemorative Lecture Prize 2024, Conchita Rábago Foundation (2024)
4. Inaugural Tengchong Science Prize, Tengchong Scientists Forum (2023)
5. Lasker~DeBakey Clinical Medical Research Award, Lasker Foundation (2022)
6. Royal Medal in Biological Sciences, The Royal Society of London (2021)
7. 2021 Breakthrough Prize in Life Sciences, The Breakthrough Prizes (2020)
8. Fudan-Zhongzhi Science Award, Fudan University & Zhongzhi Enterprise Group (2019)
9. Future Science Prize in Life Science, The Future Forum (2016)
10. King Faisal International Prize in Medicine, The King Faisal Foundation (2014)

1. Jiang P, Ma MJL, Qiao R, Shi Y, Liu J, Zhou Q, Peng W, Lam WKJ, Bai J, Choy LYL, Tsui WHA, Malki Y, Kang G, Yu SCY, Xiong D, Wong GLH, Chan LL, Wong J, Chan SL, Wong VWS, Chan KCA, Lo YMD. Holistic determination of ends of cfDNA molecules. Cell Genomics. 2026;6(3):101142. doi:10.1016/j.xgen.2026.101142.
2. Lam WKJ, Kang G, Chan CML, Lee VCT, Ma MJL, Zhou Q, Jiang P, Tse IOL, King AD, Wong KCW, Hui EP, Ma BBY, Chan ATC, Chan KCA, Lo YMD. Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma. Cancer Cell. 2025;43(4):728-739.e5. doi:10.1016/j.ccell.2025.02.002.
3. Bai J, Jiang P, Ji L, Lam WKJ, Zhou Q, Ma MJL, Ding SC, Ramakrishnan S, Wan CW, Yang TC, Yukawa M, Chan RWY, Qiao R, Yu SCY, Choy LYL, Shi Y, Wang Z, Tam THC, Law MF, Wong RSM, Wong J, Chan SL, Wong GLH, Wong VWS, Chan KCA, Lo YMD. Histone modifications of circulating nucleosomes are associated with changes in cell-free DNA fragmentation patterns. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(42):e2404058121. doi:10.1073/pnas.2404058121.
4. Zhou Q, Kang G, Jiang P, Qiao R, Lam WKJ, Yu SCY, Ma MJL, Ji L, Cheng SH, Gai W, Peng W, Shang H, Chan RWY, Chan SL, Wong GLH, Hiraki LT, Volpi S, Wong VWS, Wong J, Chiu RWK, Chan KCA, Lo YMD. Epigenetic analysis of cell-free DNA by fragmentomic profiling. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(44):e2209852119. doi:10.1073/pnas.2209852119..
5. Lo YMD, Han DSC, Jiang P, Chiu RWK. Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies. Science. 2021;372(6538). doi:10.1126/science.aaw3616.
6. Yu SCY, Jiang P, Peng W, Cheng SH, Cheung YTT, Tse OYO, Shang H, Poon LC, Leung TY, Chan KCA, Chiu RWK, Lo YMD. Single-molecule sequencing reveals a large population of long cell-free DNA molecules in maternal plasma. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(50):e2114937118. doi:10.1073/pnas.2114937118.
7. Tse OYO, Jiang P, Cheng SH, Peng W, Shang H, Wong J, Chan SL, Poon LCY, Leung TY, Chan KCA, Chiu RWK, Lo YMD. Genome-wide detection of cytosine methylation by single molecule real-time sequencing. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(5):e2019768118. doi:10.1073/pnas.2019768118.
8. Jiang P, Sun K, Peng W, Cheng SH, Ni M, Yeung PC, Heung MMS, Xie T, Shang H, Zhou Z, Chan RWY, Wong J, Wong VWS, Poon LC, Leung TY, Lam WKJ, Chan JYK, Chan HLY, Chan KCA, Chiu RWK, Lo YMD. Plasma DNA end-motif profiling as a fragmentomic marker in cancer, pregnancy, and transplantation. Cancer Discovery. 2020;10(5):664-673. doi:10.1158/2159-8290.cd-19-0622.
9. Han DSC, Ni M, Chan RWY, Chan VWH, Lui KO, Chiu RWK, Lo YMD. The biology of cell-free DNA fragmentation and the roles of DNASE1, DNASE1l3, and DFFB. The American Journal of Human Genetics. 2020;106(2):202-214. doi:10.1016/j.ajhg.2020.01.008.
10. Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, Chu SWI, Mak C, Tse IOL, Leung SYM, Chan G, Hui EP, Ma BBY, Chiu RWK, Leung SF, van Hasselt AC, Chan ATC, Lo YMD. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. New England Journal of Medicine. 2017;377(6):513-522. doi:10.1056/nejmoa1701717.
11. Jiang P, Chan CWM, Chan KCA, Cheng SH, Wong J, Wong VWS, Wong GLH, Chan SL, Mok TSK, Chan HLY, Lai PBS, Chiu RWK, Lo YMD. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(11):E1317-E1325. doi:10.1073/pnas.1500076112.
12. Sun K, Jiang P, Chan KCA, Wong J, Cheng YKY, Liang RHS, Chan WK, Ma ESK, Chan SL, Cheng SH, Chan RWY, Tong YK, Ng SSM, Wong RSM, Hui DSC, Leung TN, Leung TY, Lai PBS, Chiu RWK, Lo YMD. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(40):E5503-E5512. doi:10.1073/pnas.1508736112.
13. Chiu RWK, Akolekar R, Zheng YWL, Leung TY, Sun H, Chan KCA, Lun FMF, Go ATJI, Lau ET, To WWK, Leung WC, Tang RYK, Au-Yeung SKC, Lam H, Kung YY, Zhang X, Van Vugt JMG, Minekawa R, Tang MHY, Wang J, Oudejans CBM, Lau TK, Nicolaides KH, Lo YMD. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: Large scale validity study. BMJ. 2011;342(7790):217. doi:10.1136/bmj.c7401.
14. Lo YMD, Chan KCA, Sun H, Chen EZ, Jiang P, Lun FMF, Zheng YW, Leung TY, Lau TK, Cantor CR, Chiu RWK. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Science Translational Medicine. 2010;2(61). doi:10.1126/scitranslmed.3001720.
15. Chiu RWK, Chan KCA, Gao Y, Lau VYM, Zheng W, Leung TY, Foo CHF, Xie B, Tsui NBY, Lun FMF, Zee BCY, Lau TK, Cantor CR, Lo YMD. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(51):20458-20463. doi:10.1073/pnas.0810641105.
16. Lo YMD, Tsui NBY, Chiu RWK, Lau TK, Leung TN, Heung MMS, Gerovassili A, Jin Y, Nicolaides KH, Cantor CR, Ding C. Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nature Medicine. 2007;13(2):218-223. doi:10.1038/nm1530.
17. Lo YMD, Chan LYS, Lo KW, Leung SF, Zhang J, Chan ATC, Lee JCK, Hjelm NM, Johnson PJ, Huang DP. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Research. 1999;59(6):1188-1191.
18. Lo YMD, Zhang J, Leung TN, Lau TK, Chang AMZ, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. The American Journal of Human Genetics. 1999;64(1):218-224. doi:10.1086/302205.
19. Lo YMD, Hjelm NM, Fidler C, Sargent IL, Murphy MF, Chamberlain PF, Poon PMK, Redman CWG, Wainscoat JS. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. New England Journal of Medicine. 1998;339(24):1734-1738. doi:10.1056/nejm199812103392402.
20. Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CWG, Wainscoat JS. Presence of fetal DNA in maternal plasma and serum. The Lancet. 1997;350(9076):485-487. doi:10.1016/s0140-6736(97)02174-0.