Frank Eisenhaber


A*STAR Senior Fellow,
Laboratory of Gene Function Discovery




Our research focus is on the discovery of new biomolecular mechanisms from biological and medical data and the functional characterization of yet uncharacterized genes and pathways with theoretical/computational methods. Applications reach into medical data analysis, natural product, aging and rare diseases research. The starting point of our research are usually protein and genome sequences (typically coming from experimental of clinical collaborators) where other types of data (3D structures, expression profiles, phenotypes, medical data, etc.) can be mapped upon. Our success stories include the discovery of the SET domain methyltransferases (PMID: 10949293), ATGL (15550674), kleisins (12667442), many new protein domain functions and functional sequence patterns (for example in the GPI lipid anchor biosynthesis pathway such as the peptide synthetase activity of GPAA1 (24743167)).

In several cases, this research effort has involved the development of algorithms and software for biomolecular sequence, omics, clinical and other life science data analysis (see below). Examples are PTM and subcellular localization prediction tools for proteins (see 20221930, 20221930, 19029837, and 15575971), a sophisticated ANNOTATOR software suite for protein function discovery from sequence (27115649) or NSC, the highly cited protein surface computation algorithm (J. Comp. Chem. 16 pp. 273-284).

We discovered in 2018 that the productivity of academic life science research has drastically declined since 2000 if measured in terms of biomolecular mechanism and new gene function discovery: It is generally believed that full human genome sequencing was a watershed event in human history that boosted biomedical research, biomolecular mechanism discovery and life science applications. Yet, there is a persisting body of functionally insufficiently or completely not characterized genes (~10,000 protein-coding in the human genome) despite the availability of full genome sequences. A literature survey shows that the number of reported new protein functions had been steadily growing until 2000 but the trend reversed to a dramatic decline thereafter whereas, at the same time, the annual amount of new life science publications doubled between 2000 and 2017.

Below, we list some recent publications in A) gene function discovery studies, B) about protein functions in the GPI lipid anchor pathway, C) discovery of gene functions and new compounds in natural product research and in aging, D) about bioethics research and science history and E) methods development: Towards a unified sequence homology theory, disordered protein regions and OMICS data algorithms

Selected Publications

  • Darkness in the Human Gene and Protein Function Space: Widely Modest or Absent Illumination by the Life Science Literature and the Trend for Fewer Protein Function Discoveries Since 2000. Sinha S, Eisenhaber B, Jensen LJ, Kalbuaji B, Eisenhaber F. Proteomics. 2018 Nov;18(21-22):e1800093. doi: 10.1002/pmic.201800093. Epub 2018 Oct 30. PMID: 30265449
  • Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates. Szenker-Ravi E, Ott T, Khatoo M, de Bellaing AM, Goh WX, Chong YL, Beckers A, Kannesan D, Louvel G, Anujan P, Ravi V, Bonnard C, Moutton S, Schoen P, Fradin M, Colin E, Megarbane A, Daou L, Chehab G, Di Filippo S, Rooryck C, Deleuze JF, Boland A, Arribard N, Eker R, Tohari S, Ng AY, Rio M, Lim CT, Eisenhaber B, Eisenhaber F, Venkatesh B, Amiel J, Crollius HR, Gordon CT, Gossler A, Roy S, Attie-Bitach T, Blum M, Bouvagnet P, Reversade B. Nat Genet. 2022 Jan;54(1):62-72. doi: 10.1038/s41588-021-00970-4. Epub 2021 Dec 13. PMID: 34903892
  • Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype. Niska-Blakie J, Gopinathan L, Low KN, Kien YL, Goh CMF, Caldez MJ, Pfeiffenberger E, Jones OS, Ong CB, Kurochkin IV, Coppola V, Tessarollo L, Choi H, Kanagasundaram Y, Eisenhaber F, Maurer-Stroh S, Kaldis P. Cell Mol Life Sci. 2020 Sep;77(17):3423-3439. doi: 10.1007/s00018-019-03359-z. Epub 2019 Nov 13. PMID: 31722069
  • Charged residues next to transmembrane regions revisited: "Positive-inside rule" is complemented by the "negative inside depletion/outside enrichment rule". Baker JA, Wong WC, Eisenhaber B, Warwicker J, Eisenhaber F. BMC Biol. 2017 Jul 24;15(1):66. doi: 10.1186/s12915-017-0404-4. PMID: 28738801
  • Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites. Eisenhaber B, Sinha S, Jadalanki CK, Shitov VA, Tan QW, Sirota FL, Eisenhaber F. Biol Direct. 2021 Jan 12;16(1):4. doi: 10.1186/s13062-021-00291-w. PMID: 33436046
  • Nuclear import of a lipid-modified transcription factor: mobilization of NFAT5 isoform a by osmotic stress. Eisenhaber B, Sammer M, Lua WH, Benetka W, Liew LL, Yu W, Lee HK, Koranda M, Eisenhaber F, Adhikari S. Cell Cycle. 2011 Nov 15;10(22):3897-911. doi: 10.4161/cc.10.22.18043. Epub 2011 Nov 15. PMID: 22071693
  • The 160K Natural Organism Library, a unique resource for natural products research. Ng SB, Kanagasundaram Y, Fan H, Arumugam P, Eisenhaber B, Eisenhaber F. Nat Biotechnol. 2018 Jul 6;36(7):570-573. doi: 10.1038/nbt.4187. PMID: 29979661
  • Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723. Sinha S, Nge CE, Leong CY, Ng V, Crasta S, Alfatah M, Goh F, Low KN, Zhang H, Arumugam P, Lezhava A, Chen SL, Kanagasundaram Y, Ng SB, Eisenhaber F, Eisenhaber B. BMC Genomics. 2019 May 14;20(1):374. doi: 10.1186/s12864-019-5762-6. PMID: 31088369
  • Automated interpretation of systolic and diastolic function on the echocardiogram: a multicohort study. Tromp J, Seekings PJ, Hung CL, Iversen MB, Frost MJ, Ouwerkerk W, Jiang Z, Eisenhaber F, Goh RSM, Zhao H, Huang W, Ling LH, Sim D, Cozzone P, Richards AM, Lee HK, Solomon SD, Lam CSP, Ezekowitz JA. Lancet Digit Health. 2022 Jan;4(1):e46-e54. doi: 10.1016/S2589-7500(21)00235-1. Epub 2021 Dec 1. PMID: 34863649
  • Hypocrisy Around Medical Patient Data: Issues of Access for Biomedical Research, Data Quality, Usefulness for the Purpose and Omics Data as Game Changer. Tantoso E, Wong WC, Tay WH, Lee J, Sinha S, Eisenhaber B, Eisenhaber F. Asian Bioeth Rev. 2019 Jun 1;11(2):189-207. doi: 10.1007/s41649-019-00085-3. eCollection 2019 Jun. PMID: 33717311