Kale Research Group

Capelluto Research Group (2018)

We aim to further dissect the establishment and progression of eukaryotic symbiosis in plants and animals. We pursue this endeavor through an integrative systems biology approach. We work toward the development of novel therapeutics and diagnostics for clinically relevant fungi based upon our fundamental discoveries.

Microbe-host interactions influence all aspects of human life both directly and indirectly. These interactions may be considered beneficial, harmful, or benign, and in certain cases shift during the course of the interaction. The Kale Group's principal aim is to understand the specific evolutionary rules and constraints that establish, perpetuate, and modulate these microbial interactions at all levels of abstraction.

The laboratory is primarily interested in clinically relevant fungi, particularly Aspergillus fumigatus, a saprophytic fungus ubiquitous in nature and built environments. A. fumigatus causes a variety of disease phenotypes in humans and provides a model system to study both the role of nature and nurture in disease manifestation and progression. We investigate both host and fungal processes that determine specific disease outcome. Understanding the function and importance of a host or fungal gene in context provides an avenue to develop personalized medicine  for a given disease manifestation.

Adaptor Proteins in Endosomal Protein Trafficking

Effector proteins are viewed in part as small secreted proteins that are capable of facilitating symbiosis. We focus on the structure and function of a class of conserved effector proteins known commonly as RxLR-effectors. These effectors contain a conserved N-terminal motif of arginine--a  subset of amino acids, leucine, and arginine. Variants of this motif can be found in effector proteins from a variety of eukaryotic symbionts. Our group is particularly interested in the trafficking of these effectors from the pathogen to the host animal or plant cell via binding cell surface PtdIns-3-P, a phospholipid important in cellular trafficking and signaling.

Lipid-binding Events in the Wnt Signaling Pathway

Cellular signaling mediates all aspects of biology and is the central means by which systems at all levels of abstraction communicate and function. We are interested in how host signal transduction pathways are hijacked by microbes to facilitate symbiosis and how different signaling pathways cross- communicate to modulate a given process in a context- specific manner. These studies are carried out in collaboration with T.M. Murali and ISBET. Our goal is to utilize computational science to identify and predict novel signaling components as well as sites for signal transduction cross-talk.

Modulators of Platelet Aggregation

Lab Members


Barron, Zachary

BREU Student

Boribong, Brittany

Visiting Student

Dye, Keane

Visiting Student

Kastelberg, Bridget

BREU Student

Kite, Trenton

Visiting Student

Leung, Austin

BREU Student

Scales, Kennedi

BREU Student

Vora, Parth

GRA Student


Clark HR, Powell AB, Simmons KA, Ayubi T, Kale S. Endocytic Markers Associated with the Internalization and Processing of Aspergillus fumigatus Conidia by BEAS-2B Cells. mSphere. 2019;4(1). https://doi.org/10.1128/mSphere.00663-18.

Kale S. PenSeq: coverage you can count on. New Phytol. 2019;221(3):1177–1179. https://doi.org/10.1111/nph.15608.


Wang L, Law J, Kale SD, Murali TM, Pandey G. Large-scale protein function prediction using heterogeneous ensembles. F1000Research. 2018;7(1577). https://doi.org/10.12688/f1000research.16415.1.

Wu Y, Ma X, Pan Z, Kale S, Song Y, King H, Zhang Q, Presley C, Deng X, Wei C-I, Xiao S. Comparative genome analyses reveal sequence features reflecting distinct modes of host-adaptation between dicot and monocot powdery mildew. BMC Genomics. 2018;19(1):705. https://doi.org/10.1186/s12864-018-5069-z.

Hayes T, Rumore A, Howard B, He X, Luo M, Wuenschmann S, Chapman M, Kale S, Li L, Kita H, Lawrence CB. Innate Immunity Induced by the Major Allergen Alt a 1 From the Fungus Alternaria Is Dependent Upon Toll-Like Receptors 2/4 in Human Lung Epithelial Cells. Front Immunol. 2018;9:1507. https://doi.org/10.3389/fimmu.2018.01507.


Kale S, Ayubi T, Chung D, Tubau-Juni N, Leber A, Dang HX, Karyala S, Hontecillas R, Lawrence CB, Cramer RA, Bassaganya-Riera J. Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis. Sci Rep. 2017;7(1):17096. https://doi.org/10.1038/s41598-017-17000-1.

Bharadwaj A, Singh DP, Ritz A, Tegge AN, Poirel CL, Kraikivski P, Adames N, Luther K, Kale S, Peccoud J, Tyson JJ, Murali TM. GraphSpace: stimulating interdisciplinary collaborations in network biology. Bioinformatics. 2017;33(19):3134–3136. https://doi.org/10.1093/bioinformatics/btx382.

Kale S, Barrett C, Karyala S. Interviewed by Freemal R. Making the invisible visible: Biocomplexity Institute launches summer program in metagenomics. VT News. 2017. https://vtnews.vt.edu/articles/2017/08/bi-metagenomicsprogram.ht....

Kale SD. The masks of Avh238. NEW PHYTOLOGIST. 2017;214(1):8–10. https://doi.org/10.1111/nph.14493.

Leber A, Bassaganya-Riera J, Tubau-Juni N, Zoccoli-Rodriguez V, Lu P, Godfrey V, Kale S, Hontecillas R. Lanthionine Synthetase C-Life 2 Modulates Immune Responses to Influenza Virus Infection. Front Immunol. 2017;8:178. https://doi.org/10.3389/fimmu.2017.00178.


Maciak S, Michalak K, Kale S, Michalak P. "Nucleolar Dominance and Repression of 45S Ribosomal RNA Genes in Hybrids between Xenopus borealis and X. muelleri (2n = 36)" # "Nucleolar Dominance and Repression of 45S Ribosomal RNA Genes in Hybrids between Xenopus borealis and X. muelleri (2n=36)". Cytogenet Genome Res. 2016;149(4):290–296. https://doi.org/10.1159/000450665.

Ritz A, Poirel CL, Tegge AN, Sharp N, Simmons K, Powell A, Kale S, Murali TM. "Pathways on demand: automated reconstruction of human signaling networks" # "Pathways on demand: automated reconstruction of human signaling networks.". Npj Systems Biology And Applications. 2016;2:16002. https://doi.org/10.1038/npjsba.2016.2.

Rutledge SD, Douglas TA, Nicholson JM, Vila-Casadesus M, Kantzler CL, Wangsa D, Barroso-Vilares M, Kale S, Logarinho E, Cimini D. Selective advantage of trisomic human cells cultured in non-standard conditions. Sci Rep. 2016;6:22828. https://doi.org/10.1038/srep22828.


Blondeau K, Blaise F, Graille M, Kale S, Linglin J, Ollivier B, Labarde A, Lazar N, Daverdin G, Balesdent MH, Choi DH, Tyler BM, Rouxel T, Tilbeurgh H van, Fudal I. Crystal structure of the effector AvrLm4-7 of Leptosphaeria maculans reveals insights into its translocation into plant cells and recognition by resistance proteins. Plant J. 2015;83(4):610–624. https://doi.org/10.1111/tpj.12913.

Lu P, Hontecillas R, Abedi V, Kale S, Leber A, Heltzel C, Langowski M, Godfrey V, Philipson C, Tubau-Juni N, Carbo A, Girardin S, Uren A, Bassaganya-Riera J. Modeling-Enabled Characterization of Novel NLRX1 Ligands. PLoS One. 2015;10(12):e0145420. https://doi.org/10.1371/journal.pone.0145420.


Clark HR, Hayes TA, Kale SD. Characterizing and Measuring Endocytosis of Lipid-Binding Effectors in Mammalian Cells. Methods Enzymol. 2014;535:103–119. https://doi.org/10.1016/B978-0-12-397925-4.00007-9.


Song T, Kale SD, Arredondo FD, Shen D, Su L, Liu L, Wu Y, Wang Y, Dou D, Tyler BM. Two RxLR Avirulence Genes in Phytophthora sojae Determine Soybean Rps1k-Mediated Disease Resistance. MOLECULAR PLANT-MICROBE INTERACTIONS. 2013;26(7):711–720. https://doi.org/10.1094/MPMI-12-12-0289-R.

Tyler BM, Kale SD, Wang Q, Tao K, Clark HR, Drews K, Antignani V, Rumore A, Hayes T, Plett JM, Fudal I, Gu B, Chen Q, Affeldt KJ, Berthier E, Fischer GJ, Dou D, Shan W, Keller NP, Martin F, Rouxel T, Lawrence CB. "Microbe-Independent Entry of Oomycete RxLR Effectors and Fungal RxLR-Like Effectors Into Plant and Animal Cells Is Specific and Reproducible" # "Microbe-independent entry of oomycete RxLR effectors and fungal RxLR-like effectors into plant and animal cells is specific and reproducible". Mol Plant Microbe Interact. 2013;26(6):611–616. https://doi.org/10.1094/MPMI-02-13-0051-IA.

Sun F, Kale SD, Azurmendi HF, Li D, Tyler BM, Capelluto DG. Structural Basis for Interactions of the Phytophthora sojae RxLR Effector Avh5 with Phosphatidylinositol 3-Phosphate and for Host Cell Entry. MOLECULAR PLANT-MICROBE INTERACTIONS. 2013;26(3):330–344. https://doi.org/10.1094/MPMI-07-12-0184-R.

Bassaganya-Riera J, Kale S, Hontecillas R. Novel orally active ligands of lanthionine synthetase C-like protein 2 ameliorate influenza-related inflammation and immunopathology. 2013. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=....


Kale SD. Oomycete and fungal effector entry, a microbial Trojan horse. NEW PHYTOLOGIST. 2012;193(4):874–881. https://doi.org/10.1111/j.1469-8137.2011.03968.x.

Kale SD, Tyler BM. Identification of lipid-binding effectors. Methods in molecular biology (Clifton, NJ). 2012;835:393–414. https://doi.org/10.1007/978-1-61779-501-5_24.


Kale SD, Tyler BM. Entry of oomycete and fungal effectors into plant and animal host cells. CELLULAR MICROBIOLOGY. 2011;13(12):1839–1848. https://doi.org/10.1111/j.1462-5822.2011.01659.x.

Gu B, Kale SD, Wang Q, Wang D, Pan Q, Cao H, Meng Y, Kang Z, Tyler BM, Shan W. Rust Secreted Protein Ps87 Is Conserved in Diverse Fungal Pathogens and Contains a RXLR-like Motif Sufficient for Translocation into Plant Cells. Plos One. 2011. https://doi.org/10.1371/journal.pone.0027217.

Dong S, Yin W, Kong G, Yang X, Qutob D, Chen Q, Kale SD, Sui Y, Zhang Z, Dou D, Zheng X, Gijzen M, Tyler BM, Wang Y. Phytophthora sojae Avirulence Effector Avr3b is a Secreted NADH and ADP-ribose Pyrophosphorylase that Modulates Plant Immunity. PLoS Pathog. 2011;7(11):e1002353. https://doi.org/10.1371/journal.ppat.1002353.

Plett JM, Kemppainen M, Kale SD, Kohler A, Legue V, Brun A, Tyler BM, Pardo AG, Martin F. A Secreted Effector Protein of Laccaria bicolor Is Required for Symbiosis Development. Curr Biol. 2011;21(14):1197–1203. https://doi.org/10.1016/j.cub.2011.05.033.

Dong S, Yu D, Cui L, Qutob D, Tedman-Jones J, Kale SD, Tyler BM, Wang Y, Gijzen M. Sequence Variants of the Phytophthora sojae RXLR Effector Avr3a/5 Are Differentially Recognized by Rps3a and Rps5 in Soybean. PLOS ONE. 2011;6(7). https://doi.org/10.1371/journal.pone.0020172.

Wang Q, Han C, Ferreira AO, Yu X, Ye W, Tripathy S, Kale S, Gu B, Sheng Y, Sui Y, Wang X, Zhang Z, Cheng B, Dong S, Shan W, Zheng X, Dou D, Tyler BM, Wang Y. Transcriptional Programming and Functional Interactions within the Phytophthora sojae RXLR Effector Repertoire. Plant Cell. 2011;23(6):2064–2086. https://doi.org/10.1105/tpc.111.086082.

Kale SD, Tyler BM. Assaying effector function in planta using double-barreled particle bombardment. Methods in molecular biology (Clifton, NJ). 2011;712:153–172. https://doi.org/10.1007/978-1-61737-998-7_13.

Kale S. Unraveling the entry mechanism of oomycete and fungal effector proteins into host cells. In: 2011 Borlaug Global Rust Initiative Technical Workshop. Borlaug Global Rust Initiative; 2011:82–88.


Kale SD, Gu B, Capelluto DG, Dou D, Feldman E, Rumore A, Arredondo FD, Hanlon R, Fudal I, Rouxel T, Lawrence CB, Shan W, Tyler BM. External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cells. Cell. 2010;142(2):284–295. https://doi.org/10.1016/j.cell.2010.06.008.

Dou D, Kale SD, Liu T, Tang Q, Wang X, Arredondo FD, Basnayake S, Whisson S, Drenth A, Maclean D, Tyler BM. Different domains of Phytophthora sojae effector Avr4/6 are recognized by soybean resistance genes Rps4 and Rps6. Mol Plant Microbe Interact. 2010;23(4):425–435. https://doi.org/10.1094/MPMI-23-4-0425.


Dou D, Kale SD, Wang X, Jiang RH, Bruce NA, Arredondo FD, Zhang X, Tyler BM. RXLR-mediated entry of Phytophthora sojae effector Avr1b into soybean cells does not require pathogen-encoded machinery. Plant Cell. 2008;20(7):1930–1947. https://doi.org/10.1105/tpc.107.056093.

Dou D, Kale SD, Wang X, Chen Y, Wang Q, Jiang RH, Arredondo FD, Anderson RG, Thakur PB, McDowell JM, Wang Y, Tyler BM. Conserved C-terminal motifs required for avirulence and suppression of cell death by Phytophthora sojae effector Avr1b. Plant Cell. 2008;20(4):1118–1133. https://doi.org/10.1105/tpc.107.057067.


Tyler BM, Dou D, Jiang RHY, Wang X, Kale SD, Arredondo F, Tripathy S. Effector repertoire of Phytophthora sojae: Structural and functional genomics. PHYTOPATHOLOGY. 2007;97(7):S146–S146. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=....