Emeritus Faculty
bc201@gate.sinica.edu.tw
Inn-Ho Tsai RESEARCH FELLOW

Research

I started to study the venom proteins of Taiwanese cobra and krait in 1977. I also studied the midgut chymotrypsin and trypsin and the hemolymph clottable protein and transglutaminase of Penaes shrimps. Later, we used Molecular Biology tools to study snake venom. Venomous snakes of medical or biological importance (e.g. habu, king cobra), monotypic (e.g. Azemiops, Deinagkistrodon), endemic to Taiwan (e.g. T. gracilis), or of high biodiversity usually attracted me. We have used FPLC, RP-HPLC, LC-MS/MS, and cDNA cloning/sequencing to study venom proteins; and analyzed the in vitro and in vivo functions. Transcriptomics, Proteomics, Glycomics and Bioinformatics have been included in our research in recent years. Our lab. has solved many toxin sequences and deposited in Genbank; and published about 80 papers on venom toxins before 2020.

Snake toxin-families have undergone rapid evolution and venom variations are associated with phylogeographic and environmental changes of the snakes during past 40~6 million years. We have explored and compared the geographic variations of the following venom species: (1) Habu P. mucrosquamatus from North and South Taiwan, and different species of Protobothrops; (2) Bamboo viper T. stejnegeri from seven regions over Taiwan; (3) Malayan pitviper C. rhodostoma from five S.E. Asian countries; (4) Rattlesnake C. v. viridis inhabiting different States of USA, from Montana to New Mexico; (5) Russell’s vipers (D. russellii and D. siamensis); Daboia venom from Myanmar and eastern India are similar to each other, while those from Pakistan, Indonesia islands, Sri Lanka, Thailand, china and Taiwan show clear differences; (6) King cobra from four Asian countries and China; (7) E. India B. fasciatus. We cloned/sequenced the cDNAs encoding ten venom PLA2 paralogs and four 3Finger-toxins and confirmed that the PLA2 sequences completely match the previous Edman-degradation results by T.B. Low’s lab. of our institute (possibly used Thailand B. fasciatus venom), only the 3Finger-toxins show great geographic variations. (8) Temple viper T. wagleri of two Malayan/Asian regions. Significant geographic variations in viperid and king-cobra venom phospholipases A2 have been demonstrated and the findings may help the snakebite treatment and antivenin formulation.

We also succeeded in the recombinant expression and site-directed mutagenesis of a habu phospholipase-neurotoxin, and performed “knock-out” study of each of the N-glycosylation site in acutobin (the thrombin like enzyme from Deinagkistrodon). Both projects are expensive and long-term, but the results are not much appreciated. We have also collaborated with Prof. Khoo K.H. on a genus-wide comparison of the glycan-profiles of representative viperid venoms; MS/MS and glycopeptide analysis revealed unique disialylated multiantennary N-glycans on acutobin. There have been some exciting “first time” findings in my lab., including: (A) Cheng A.C. showed that a Kunitz-type protease inhibitor from Russell’s viper is a heparin-dependent inhibitor of “activated protein C”; (B) Chen H.S. discovered a thrombin-binding snaclect and clarified its anticoagulant mechanism; (C) Tsai S.H. showed that K49-PLA2 of T. stejnegeri binds LPS very strongly, and serve as an antibacterial agents; (D) Collaborating with Yang Z.M. (Xanxii Normal Univ., China) we discovered that crotoxin-like neurotoxic PLA2 dimers are present in G. intermedius venom.

Degrees and Positions Held

  • 1979 – 1980   Postdoctoral Res. fellow, Dept. Biochemistry, U. of Chicago
  • 1976 – 1977   Postdoctoral Res. , Thiman Labs., UC, Santa Cruz, USA
  • 1971 – 1976   Ph.D., Dept. Chemistry , Northwestern University, USA
  • 1967 – 1971   B.S., Agricultural Chemistry , National Taiwan University
  • 1988 – 2014   Research Fellow, Inst. Biological Chemistry, Academia Sinica, Taiwan
  • 1988 – 2014   Professor, Inst. Biochemical Sciences, National Taiwan University, Taiwan
  • 1999 – 2002   Director , Inst. Biochemical Sciences, National Taiwan University, Taiwan
  • 1996 – 1996   Visiting Professor, Dept. of Chem. Engine., Johns Hopkins Univ., USA
  • 1993 – 1995 Deputy Director , Institute of Biological Chemistry, Academia Sinica, Taiwan
  • 1988 – 1988 Visiting scholar, Dept. Struct. & Cell. Biol., Univ. Texas, San Antonio, USA
  • 1977 – 1988 Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan

Selected Publications

Structural and bioinformatic analyses of Azemiops venom serine proteases reveal close phylogeographic relationships to pitvipers from eastern China and the New World. 
Tsai IH*, Wang YM, Lin SW, Huang KF 
Toxicon (2021)

Serine protease isoforms in Gloydius intermedius venom: Full sequences, molecular phylogeny and evolutionary implications. 
Yang ZM, Yu H, Liu ZZ, Pei JZ, Yang YE, Yan SX, Zhang C, Zhao WL, Wang ZZ, Wang YM, Tsai IH
J. Proteomics (2017)

Structures and functions of crotoxin-like heterodimers and acidic phospholipases A2 from Gloydius intermedius venom: insights into the origin of neurotoxic-type rattlesnakes. 
Yang ZM, Guo Q, Ma ZR, Chen Y, Wang ZZ, Wang XM, Wang YM, Tsai IH
J. Proteomics (2015)

Correlation between the glycan variations and defibrinogenating activities of acutobin and its recombinant glycoforms. 
Wang YM, Tsai IH*, Chen JM, Cheng AC, Khoo KH 
PLoS ONE (2014)

Functional proteomic approach to discover geographic variations of king cobra venoms from Southeast Asia and China. 
Chang HC, Tsai TS, Tsai IH
J. Proteomics (2013)

A novel heparin-dependent inhibitor of activated protein C that potentiates consumptive coagulopathy in Russell’s viper envenomation. 
Cheng AC, Wu HL, Shi GY, Tsai IH
J. Biol. Chem. (2012)

Mutagenesis analyses explore residues responsible for the neurotoxic and anticoagulant activities of Trimucrotoxin, a pit-viper venom Asn6-phospholipase A2. 
Tsai IH*, Wang YM, Hseu MJ 
Biochimie (2011)

Binding of a venom Lys-49 phospholipase A2 to LPS and suppression of its effects on mouse macrophages. 
Tsai SH, Chen YC, Chen L, Wang YM, Tsai IH
Toxicon (2007)

Venom phospholipases of Russell's vipers from Myanmar and eastern India—Cloning, characterization and phylogeographic analysis. 
Tsai IH*, Tsai HY, Wang YM, Tun-Pe, Warrell DA 
Biochim. Biophys. Acta (2007)

Sequences, geographic variations and molecular phylogeny of venom phospholipases and threefinger toxins of eastern India Bungarus fasciatus and kinetic analyses of its Pro31 phospholipases A2. 
Tsai IH*, Tsai HY, Saha A, Gomes A 
FEBS J. (2007)

Molecular evolution and structure-function relationships of crotoxin-like and asparagine 6-containing phospholipases A2 in pit viper venoms. 
Chen YH, Wang YM, Hseu MJ, Tsai IH
Biochem. J. (2004)

Venom phospholipases A2 of bamboo viper (Trimeresurus stejnegeri): molecular characterization, geographic variations and evidence of multiple ancestries. 
Tsai IH*, Wang YM, Chen YH, Tsai TS, Tu MC 
Biochem. J. (2004)

Serine protease isoforms of Deinagkistrodon acutus venom: cloning, sequencing and phylogenetic analysis. 
Wang YM, Wang SR, Tsai IH
Biochem. J. (2001)

Purification, cloning and sequence analyses for pro-metalloprotease-disintegrin variants from Deinagistrodon acutus venom and subclassification of the small venom metalloproteases. 
Tsai IH*, Wang YM, Chiang TY, Chen YL, Huang RJ 
Eur. J. Biochem. (2000)

Characterization and molecular cloning of neurotoxic phospholipases A2 from Taiwan viper (Vipera russelli formosensis). 
Wang YM, Lu PJ, Ho CL, Tsai IH
Eur. J. Biochem. (1992)

Publication List