Teh-hui Kao

About Me

I received a B.S. degree in Chemistry from National Taiwan University, and a Ph.D. degree in Chemistry (Physical Biochemistry) from Yale University.  My Ph.D. research was conducted in the lab of the late Dr. Donald Crothers on the use of temperature-jump relaxation kinetics and other biophysical techniques to study high-order structures of E. coli 5S rRNA.  I did postdoctoral research with the late Dr. James Ofengand at the Roche Institute of Molecular Biology on the use of photoaffinity labeling to study the interaction between elongation factor Tu and Phe-tRNA.  I then did postdoctoral research with the late Dr. Ray Wu of the Section of Biochemistry, Molecular and Cell Biology, Cornell University on the cloning and sequencing of several plant mitochondrial and chloroplast genes.  Through collaboration, I also worked on the cloning and sequencing of an S-locus gene of self-incompatible Brassica oleraceae.  I joined the department (then named Department of Molecular and Cell Biology) as Assistant Professor in August 1986.  I was promoted to Associate Professor in 1992 and Full Professor in 1996.  I was named Distinguished Professor of Biochemistry and Molecular Biology in 2013.  My research over the past more than three decades has focused on the self-incompatibility system possessed by Petunia and many other species in the nightshade family (Solanaceae) and several other flowering plant families.  My major teaching has been the Honors section of the second semester of General Biochemistry, which I have been teaching since spring 1988.  In addition to research and teaching, I have been serving as Chair of the Intercollege Graduate Degree Program in Plant Biology since June 1999.  In my spare time, I enjoy listening to classical music and watching Penn State sports.

Department or University Committees

• Honors Advisors Committee (BMB)
  
   
• Commencement Attendance Committee (BMB)
  
   
• Post-Tenure Review Committee (Chair, BMB)
  
   
• Promotion and Tenure Committee (BMB)
  
   
• Peer Teaching Evaluation Committee (BMB)
  
   
• Department Head Executive Committee (BMB)
  
   
• Graduate Affairs Committee (BMB)
  
   
• Undergraduate Affairs Committee (BMB)
  
   
• Faculty Scholar Medal Nomination Review Committee (Eberly College of Science)
  
   
• Promotion and Tenure Committee (Eberly College of Science)
  
   
• Kitchen Cabinet (Huck)
  
   
• Task Force to Review Life Sciences Graduate Education (Graduate School)
  
   
• Graduate Council (University)
  
   
• Task Force for a Sustainable Funding Model for Intercollege Graduate Degree Programs (University)
  
   
• Life and Health Science Selection Panel for Faculty Scholar Medal (University)  

Program or Department Affiliations

Editorial Boards

Research Interest

My lab has a long-term interest in the study of self-incompatibility (SI), a self/non-self recognition mechanism between pollen and pistils, which was first well documented by Charles Darwin in a monograph published in 1865. Most flowering plants produce bisexual flowers with the pistil and anthers located in close proximity in the same flower. This arrangement is conducive to self-fertilization, resulting in inbreeding, which reduces fitness in progeny and genetic diversity in the species. SI evolved millions of years ago to allow the pistil to distinguish between self (genetically related) pollen and non-self (genetically unrelated) pollen. Self pollen is rejected by the pistil to prevent inbreeding, whereas non-self pollen is accepted by the pistil to promote out-crossing. Self/non-self recognition between pollen and pistil is controlled by the highly polymorphic S-locus, which has a large number of variants (haplotypes), e.g., more than 30 S-haplotypes have been identified in Petunia. The lab is using Petunia inflata (a wild relative of garden petunia) as a model to study the molecular basis and biochemical mechanism of SI. We have identified the S-RNase gene that controls the pistil function in SI and 17 S-locus F-box (SLF) genes that collectively control the pollen function in SI. We have used an in vivo functional assay to determine how a single polymorphic S-RNase and multiple polymorphic SLF proteins interact in the cytosol of the pollen tube to result in growth inhibition of self-pollen tubes, but no growth inhibition of non-self pollen tubes, in the pistil. A model involving ubiquitin-mediated protein degradation has been proposed, and we have so far verified several of its predictions by a variety of approaches, including CRISPR/Cas9 genome editing.

Research Summary

Mechanism of self/non-self recognition between pollen and pistil in self-incompatible plants

Self-incompatibility (SI) is a self/non-self recognition mechanism that allows the pistil of flowering plants producing bisexual flowers to distinguish between self (genetically related) and non-self (genetically unrelated) pollen to prevent inbreeding and promote out-crossing.  We use Petunia inflata (a wild species, one of the progenitor species of garden petunia) as a model to study the SI mechanism possessed by Solanaceae and two other families of flowering plants.  Here, SI is controlled by the highly polymorphic S-locus.  If the S-haplotype of haploid pollen matches either S-haplotype of the diploid pistil, the pollen is recognized as self-pollen and the growth of self-pollen tubes in the style is inhibited; if the S-haplotype of pollen is different from both S-haplotypes of the pistil, the pollen is recognized as non-self pollen and their tubes are allowed to grow down through the style to the ovary to effect fertilization.

We are interested in two fundamental questions: How does a pistil distinguish between self and non-self pollen?  How does the self and non-self recognition lead to growth arrest of self-pollen tubes in the style?  Over the past more than three decades of research, we have used a number of approaches, including an in vivo functional approach, to understand the biochemical and molecular bases of SI.  Some of the key findings are listed below: (1) using gain-of-function and loss-of-function approaches, the polymorphic S-RNase gene was identified as the gene that regulates pistil specificity in SI (Lee et al. Nature 367: 560-563, 1994); (2) using site-directed mutagenesis, it was shown that the RNase activity of S-RNase is essential for the function of S-RNase in rejection of self-pollen (Huang et al. Plant Cell 6: 1021-1028, 1994); (3) an S-locus F-box (SLF) gene, PiSLF1 (now named SLF1), was identified by sequencing Bacterial Artificial Chromosome (BAC) clones spanning a 328-kb region containing S₂-RNase (McCubbin et al. Genome 43: 820-826, 2000; Wang et al. Plant Mol Biol 54: 724-742, 2004), and using an in vivo functional approach, SLF1 was shown to be involved in regulating pollen specificity (Sijacic et al. Nature 429: 302-305, 2004); (4) using RNAseq and pollen transcriptome analyses, a total of 17 pollen-specific polymorphic SLF genes (including SLF1) were identified in both S₂-haplotype and S₃-haplotype (Williams et al. Plant Cell 26: 2873-2888, 2014); (5) using coimmunoprecipitation and mass spectrometry, all 17 SLF proteins of S₂ and S₃ pollen were shown to be assembled into similar SCF complexes, which also contain PiSSK1 (a pollen-specific Skp1-like protein), PiRBX1 (a RING-finger protein) and PiCUL1-P (a pollen-specific Cullin1) (Li et al. Plant Reprod 27: 31-45, 2014; Li et al. Plant J 87: 606-616, 2016); (6) it was discovered that SLF proteins are themselves subject to ubiquitin-mediated degradation by the 26S proteasome (Sun et al. Plant J 83: 213-223, 2015), and pollen proteins that may regulate the dynamic life cycle of SCF^SLF complexes were identified.

A current focus is on testing the predictions of the collaborative non-self recognition model formulated after the discovery that more than one SLF gene regulates pollen specificity (Kubo et al. Science 330: 796-799, 2010).  According to this model, for a given S-haplotype, each SLF interacts with a subset of its non-self S-RNases, and all SLF proteins that constitute the pollen specificity determinant collectively interact with the entire suite of their non-self S-RNases to mediate ubiquitination and degradation, allowing cross compatible pollination.  However, none of the SLF proteins interact with their self S-RNase, allowing the self S-RNase to inhibit pollen tube growth.  Over the past few years, we have been using an in vivo functional assay to establish comprehensive interaction relationships between 17 SLF proteins of S₂-haplotype and S₃-haplotype, and 11 S-RNases, and have so far established a total of 155 interaction relationships: 125 between these 11 S-RNases and 17 SLF proteins of S₂ haplotype, and 30 between 9 of these 11 S-RNases and 5 of the SLF proteins of S₃ haplotype.  As predicted by the collaborative non-self-recognition model, none of the 17 SLF proteins of S₂ pollen interact with their self S-RNase, S₂-RNase.  Among the 17 SLF proteins, SLF1 is the only one that interacts with S₃-RNase, but in contrast, both SLF1 and SLF2 interact with S₇-RNase, and both SLF1 and SLF5 interact with S₁₂-RNase.  So, there is a fail-safe strategy for detoxifying S₇-RNase and S₁₂-RNase (Sun and Kao Plant Cell 25: 470-485, 2013; Williams et al. Mol Plant 7: 567-569, 2014; Sun et al. 2018).  To verify the interaction relationships established by the genetic approach, we have used CRISPR/Cas9 genome editing to knock out S₂-SLF1 in S₂ pollen to examine the effect on the SI behavior of the mutant pollen.  All the results are consistent with the prediction of the collaborative non-self recognition model (Sun et al. 2018).  We have used the chimeric gene approach to identify amino acids of SLF proteins involved in differential interactions with S-RNases (Wu et al. Plant Cell Physiol 59: 234-247, 2018).  We have also used CRISPR/Cas9 genome editing to knock out genes encoding pollen-specific PiSSK1 and PiCUL1-P of SCF^SLF complexes, and so far we have shown that PiSSK1 is specifically involved in SI and required for cross-compatible pollination (Sun and Kao Plant Reprod 31: 129-143, 2018).  

Another ongoing project is to examine whether PiDCN1, PiUBC12, PiCAND1 and PiUPL1 are involved in regulating the dynamics of the SCF^SLF complex.  We hypothesize that PiCAND1 causes dissociation of the complex, and after PiSSK1 and SLF are released, PiUPL1, in conjunction with other enzymes, mediates ubiquitination and degradation of SLF.  

We are also interested in the structural and gene organization of the S-locus.  We have determined ~3.1 Mb of the S₂-locus region that contains the 17 SLF genes and S-RNase gene, and identified a number of pollen and/or pistil expressed genes that are trapped in this sub-centromeric region where recombination is highly suppressed.  We would like to know whether any of these genes is involved in SI or other reproductive processes.  

All the information gained from our research will be valuable for ultimate understanding of the biochemical, molecular, and structural bases of this complex and fascinating self/non-self recognition system, which is thought to have played a vital role in the evolutionary success of flowering plants.

Honors and Awards

• Suzuki and Yabuta Foundation Lectureship, Tokyo University, September 1993
  
   
• Visiting Professor Fellowship (6 months in 1995), Japan Society for the Promotion of Science (declined)
  
   
• Dutch Royal Society of Botany Lecturer, 1994
  
   
• Research featured on cover of a Feb. 1994 issue of Nature chosen as one of the top 75 science stories in 1994 by Discover magazine
  
   
• Faculty Scholar Medal in Life and Health Sciences, Penn State University, 1995
  
   
• Daniel R. Tershak Memorial Teaching Award, Department of Biochemistry and Molecular Biology,1998
  
   
• Kathryn Barnes Memorial Lecture in Plant Biology, University of Chicago, 2000
  
   
• Graduate Program Chair Leadership Award, Penn State University, 2006
  
   
• Excellence in Honors Teaching Award, Schreyer Honors College, Penn State University, 2008
  
   
• Distinguished Professor of Biochemistry and Molecular Biology, Appointed by President of Penn State University, 2013
  
   
• Excellence in Teaching Award, Penn State Chapter of the National Society of Leadership and Success, 2014 
  
   
• Elected Academician (in the Life Sciences Division) of Academia Sinica, Taiwan, 2014
  
   
• Elected Fellow, American Association for the Advancement of Science, 2014

Selected Publications

• Ai Y, Singh A, Coleman CE, Ioerger TR, Kheyr-Pour A, Kao T-h (1990). Self-incompatibility in Petunia inflata: isolation and characterization of cDNAs encoding three S-allele-associated proteins. Sex Plant Reprod 3: 130-138
  
   
• Ioerger TR, Clark AG, Kao T-h (1990). Polymorphism at the self-incompatibility locus in Solanaceae predates speciation. Proc Natl Acad Sci USA 87: 9732-9735
  
   
• Ioerger TR, Gohlke JR, Xu B, Kao T-h (1991). Primary structural features of the self-incompatibility protein in Solanaceae. Sex Plant Reprod 4: 81-87
  
   
• Singh A, Ai Y, Kao T-h (1991). Characterization of ribonuclease activity of three S-allele-associated proteins of Petunia inflata. Plant Physiol 96: 61-68
  
   
• Clark AG, Kao T-h (1991). Excess nonsynonymous substitution at shared polymorphic sites among self-incompatibility alleles of Solanaceae. Proc Natl Acad Sci USA 88: 9823-9827
  
   
• Coleman CE, Kao T-h (1992). The flanking regions of two Petunia inflata S-alleles are heterogeneous and contain repetitive sequences. Plant Mol Biol 18: 725-737
  
   
• Singh A, Evensen KB, Kao T-h (1992). Ethylene synthesis and floral senescence following compatible and incompatible pollinations in Petunia inflata. Plant Physiol 98: 38-45
  
   
• Lee H-S, Huang S, Kao T-h (1994). S proteins control rejection of incompatible pollen in  Petunia inflata. Nature 367: 560-563 (cover)
  
   
• Mu J-H, Lee H-S, Kao T-h (1994). Characterization of a pollen-expressed receptor-like kinase gene of Petunia inflata and the activity of its encoded kinase. Plant Cell 6: 709-721
  
   
• Clark AG, Kao T-h (1994). Self-incompatibility: theoretical concepts and evolution. In "Genetic Control of Self-Incompatibility and Reproductive Development in Flowering Plants" (Williams E G, Knox RB, Clarke AE eds), pp 220-242, Kluwer Academic Publishers, Dordrecht, Netherlands
  
   
• Huang S, Lee H-S, Karunanandaa B, Kao T-h (1994). Ribonuclease activity of Petunia inflata S proteins is essential for rejection of self-pollen. Plant Cell 6: 1021-1028
  
   
• Karunanandaa B, Huang S, Kao T-h (1994). Carbohydrate moiety of the Petunia inflata S₃ Protein is not required for self-incompatibility interactions between pollen and pistil. Plant Cell 6: 1933-1940
  
   
• Lee H-S, Karunanandaa B, McCubbin AG, Gilroy S, Kao T-h (1996). PRK1, a receptor-likeKinase of Petunia inflata, is essential for post-meiotic development of pollen. Plant J 9: 613-624
  
   
• Kao T-h, McCubbin AG (1996). How flowering plants discriminate between self and non-self pollen to prevent inbreeding. Proc Natl Acad Sci USA 93: 12059-12065
  
   
• McCubbin AG, Chung Y-Y, Kao T-h (1997). A mutant S₃ RNase of Petunia inflata lacking RNase activity has an allele-specific dominant negative effect on self-incompatibility interactions. Plant Cell 9: 85-95
  
   
• Marc J, Granger CL, Brincat J, Fisher DD, Kao T-h, McCubbin AG, Cyr RJ (1998). Use of a GFP-MAP4 reporter gene for visualizing cortical microtubule rearrangements in living epidermal cells. Plant Cell 10: 1927-1940
  
   
• McCubbin AG, Wang X, Kao T-h (2000). Identification of self-incompatibility (S-) locus linked pollen cDNA markers in Petunia inflata. Genome 43: 619-627
  
   
• McCubbin AG, Zuniga C, Kao T-h (2000). Construction of a bacterial artificial chromosome library of Petunia inflata and the identification of large genomic fragments linked to the self-incompatibility (S-) locus. Genome 43: 820-826
  
   
• Wang X, Hughes AL, Tsukamoto T, Ando T, Kao T-h (2001). Evidence that intragenic recombination contributes to allelic diversity of the S-RNase gene at the self-incompatibility (S) locus in Petunia inflata. Plant Physiol 125: 1012-1022
  
   
• Fasano JM, Swanson SJ, Blancaflor EB, Dowd PE, Kao T-h, Gilroy S (2001). Changes in root Cap pH are required for the gravity response of the Arabidopsis root. Plant Cell 13: 907-921
  
   
• Wang Y, Wang X, McCubbin AG, Kao T-h (2003). Genetic mapping and molecular characterization of the self-incompatibility (S-) locus in Petunia inflata. Plant Mol Biol 53: 565-580
  
   
• Kao T-h, Tsukamoto T (2004). The molecular and genetic bases of S-RNase-based self-incompatibility. Plant Cell 16: S72-83
  
   
• Sijacic P, Wang X, Skirpan AL, Wang Y, Dowd PE, McCubbin AG, Huang S, Kao T-h (2004). Identification of the pollen determinant of S-RNase-mediated self-incompatibility. Nature 429: 302-305
  
   
• Wang Y, Tsukamoto T, Yi K-w, Wang X, Huang S, McCubbin AG, Kao T-h (2004). Chromosome walking in the Petunia inflata self-incompatibility (S-) locus and gene  identification in an 881-kb contig containing S₂-RNase. Plant Mol Biol 54: 727-742
  
   
• Tsukamoto T, Ando T, Watanabe H, Marchesi E, Kao T-h (2005). Duplication of the S-locus F-box gene is associated with breakdown of pollen function in an S-haplotype identified in a natural population of self-incompatible Petunia axillaries. Plant Mol Biol 57: 141-153
  
   
• Dowd PE, Coursol S, Skirpan AL, Kao T-h, Gilroy S (2006). Petunia phospholipase C1 is involved in pollen tube growth. Plant Cell 18: 1438-1453
  
   
• Hua Z, Kao T-h (2006). Identification and characterization of components of a putative PiSLF-containing E3 ligase complex involved in S-RNase-based self-incompatibility. Plant Cell 18: 2531-2553
  
   
• Hua Z, Meng X, Kao T-h (2007). Comparison of Petunia inflata S-locus F-box protein (Pi SLF) and Pi SLF-like proteins reveals its unique function in S-RNase-based self-incompatibility. Plant Cell 19: 3593-3609
  
   
• Hua Z, Kao T-h (2008). Identification of major lysine residues of S₃-RNase of Petunia inflata involved in ubiquitin-26S proteasome-mediated degradation in vitro. Plant J 54: 1094-1104 
  
   
• Kubo K-I, Entani T, Takara A, Wang N, Fields AM, Hua Z, Toyoda M, Kawashima S-i, Ando T, Isogai A, Kao T-h, Takayama S (2010). Collaborative non-self recognition in S-RNase-based self-incompatibility. Science 330: 796-799
  
   
• Sun P, Kao T-h (2013).  Self-incompatibility in Petunia inflata: the relationship between a self-incompatibility locus F-box protein and its non-self S-RNases. Plant Cell 25: 470-485
• Williams JS, Natale CA, Wang N, Li S, Brubaker TR, Sun P, Kao T-h (2014). Four previously identified Petunia inflata S-locus-F-box genes are involved in pollen specificity in self-incompatibility. Mol Plant 7: 567-569
  
   
• Li S, Sun P, Williams JS, Kao T-h (2014). Identification of the self-incompatibility locus F-box protein-containing complex in Petunia inflata. Plant Reprod 27: 31-45
  
   
• Williams JS, Der JP, dePamphilis CW, Kao T-h (2014). Transcriptome analysis reveals the same 17 S-locus F-box genes in two haplotypes of the self-incompatibility locus of Petunia  inflata. Plant Cell 26: 2873-2888
  
   
• Williams JS, Wu L, Li S, Sun P, Kao T-h (2015). Insight into S-RNase-based self-incompatibility in Petunia: recent findings and future directions. Front Plant Sci doi:10.3389/fpls.2015.00041 
  
   
• Sun P, Li S, Lu D, Williams JS, Kao T-h (2015). Pollen S-locus F-box proteins of Petunia involved in S-RNase-based self-incompatibility are themselves subject to ubiquitin-mediated degradation. Plant J 83: 213-223
  
   
• Li S, Williams JS, Sun P, Kao T-h (2016). All 17 S-locus F-box proteins of S₂- and S₃-haplotypes of Petunia inflata are assembled into similar SCF complexes with specific function in self-incompatibility. Plant J 87: 606-616
  
   
• Wu L, Williams JS, Wang N, Khatri WA, San Román D, Kao T-h (2018). Use of domain-swapping to identify candidate amino acids involved in differential interactions between two allelic variants of type-1 S-locus F-box protein and S₃-RNase in Petunia inflata.  Plant Cell Physiol 59: 234-247 doi.org/10.1093/pcp/pcx176  
  
   
• Sun L, Kao T-h (2018). CRISPR/Cas9-mediated knockout of PiSSK1 reveals essential role of S-locus F-box protein-containing SCF complex in recognition of non-self S-RNases duringcross-compatible pollination in self-incompatible Petunia inflata. Plant Reprod 31: 129-143 doi.org/10.1007/s00497-017-0314-1 
  
   
• Sun L, Williams JS, Li S, Wu L, Khatri WA, Stone PG, Keebaugh MD, Kao T-h (2018). S-Locus F-Box proteins are solely responsible for S-RNase-based self-incompatibility of Petunia pollen. Plant Cell 30: doi:10.1105/tpc.18.00615
• Wu L, Williams JS, Sun L, Kao T-h (2020). Sequence analysis of the Petunia inflata S-locus region containing 17 S-locus F-box genes and the S-RNase gene involved in self-incompatibility. Plant J 104: 1348-1368, doi:10.1111/tpj.15005  
• Sun L, Cao S, Zheng N, Kao T-h (2023). Analyses of Cullin1 homologs reveal functional redundancy in S-RNase-based self-incompatibility and evolutionary relationships in eudicots. Plant Cell, doi: 10.1093/plcell/koac357  

For more publications, see https://scholar.google.com/citations?user=L9cC5tIAAAAJ&hl=en&oi=ao