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Jon C. Houtman, PhD

Associate Professor of Internal Medicine - Immunology
Associate Professor of Microbiology and Immunology
Associate Director for Career Enhancement, Holden Comprehensive Cancer Center
Faculty Director, Human Immunology Core

Contact Information

Primary Office
2210 Medical Education Research Facility (MERF)
375 Newton Rd
Iowa City, IA 52242

2234B Medical Education Research Facility (MERF)
375 Newton Rd
Iowa City, IA 52242


BA, Biology and Chemistry, University of Minnesota, Morris
PhD, Cellular and Molecular Biology, University of Wisconsin-Madison
Postdoctoral Fellow, Molecular Immunology, National Cancer Institute/NIH/DHHS

Education/Training Program Affiliations

Biomedical Science Program, Cancer Biology Graduate Program, Department of Microbiology Graduate Program, Interdisciplinary Graduate Program in Immunology, Interdisciplinary Graduate Program in Molecular Medicine, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center for Immunology and Immune-based Diseases, Holden Comprehensive Cancer Center, Institute for Clinical and Translational Science

Research Summary

T cell activation is critical for the ability of the human immune system to fight pathogen infections and to eliminate malignant cells. However, inappropriate or aberrant T cell induction drives the initiation and progression of numerous human diseases, including T cell lymphoma/leukemia, human malignancies, autoimmune disorders, cardiovascular disease, and transplant rejection. The main stimulatory receptor in human T cells is the T cell receptor (TCR). Upon TCR activation, several intracellular signal transduction pathways which control changes in T cell function are stimulated. Because of their critical role in T cell activation, it is vital that we understand the regulation, formation and function of these signaling pathways in order to develop new treatments for diseases linked to aberrant T cell activation and to understand how current treatments affect these pathways. The goal of my laboratory is to understand the molecular mechanism of the formation of the multiprotein signaling complexes that occur after TCR and to investigate the ability of therapeutic agents to alter TCR signaling. Currently, my laboratory is working on two main projects.

Project 1-Role of GRB2 in TCR signaling pathways: Upon TCR activation, the adaptor protein LAT forms large multiprotein oligomers that contain >50 LAT proteins and its binding partners. The clustering of LAT is critical for the initiation of downstream signaling, especially the influx of cytoplasmic calcium. We have shown that the dimerization of GRB2 by SH3 domain ligands, in conjunction with its multivalent interaction with LAT, leads to the oligomerization of LAT. The objective of this project is to comprehensively examine how GRB2 regulates the activation of human T cells. We are using biophysical, biochemical, imaging and cellular tools to examine the interaction of GRB2 with SH2 and SH3 domain ligands and the ability of GRB2 to regulate signaling events at LAT. The information gained from these studies will allow us to significantly advance our understanding of how GRB2 regulates human T cell function. Since GRB2 is also involved in the progression of most human malignancies, these studies will also provide insight into cancer progression and potential treatments for cancer.

Project 2-Impact of GML on human T cell activation: Glycerol monolaurate (GML) is a monoglyceride that is naturally produced upon ingestion of milk products and foods containing palm oils, such as coconut oil. GML has well described anti-microbial properties and is widely used in industrial and homeopathic settings as an anti-microbial agent. It is also currently under clinical use as a preventative agent for toxic shock syndrome and under clinical trials as a prophylactic for HIV transmission and an antimicrobial agent. Due to its widespread use the majority of people in the US and the world encounter GML daily. However, few studies have examined the effects of GML on human T cell function. The purpose of the project is to investigate how GML modulates human T cell activation and downstream function. GML appears to disrupt membrane complexes at LAT and the B cell receptor, resulting in reduced signaling and downstream function. In addition, we found that GML suppress mitochondrial function and alters metabolic flux in T cells. Finally, we are testing derivatives of GML to identify a molecule with better pharmacological properties. These studies suggest that along with its anti-microbial properties, GML may also be a novel and clinically relevant immunomodulatory agent. This information is critical to identify if GML is a immunosuppressant that could be used to modulate T cell function during the treatment of autoimmune diseases and human malignancies.


Tremblay, M. M., Ollinger, T. & Houtman JCD, (2020). The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions. Cellular signalling, 76, 109790. PMID: 32979494.

Salimi, H., Johnson, J., Flores, M. G., Zhang, M. S., O'Malley, Y. Q., Houtman, J. C., Schlievert, P. M. & Haim, H. (2019). The lipid membrane of HIV-1 stabilizes the viral envelope glycoproteins and modulates their sensitivity to antibody neutralization. The Journal of biological chemistry. PMID: 31757809.

Sieng, M., Hayes, M. P., O'Brien, J. B., Andrew Fowler, C., Houtman, J. C., Roman, D. L. & Lyon, A. M. (2019). High-resolution structure of RGS17 suggests a role for Ca2+ in promoting the GTPase-activating protein activity by RZ subfamily members. The Journal of biological chemistry, 294(20), 8148-8160. PMID: 30940727.

Jensen, I. J., Winborn, C. S., Fosdick, M. G., Shao, P., Tremblay, M. M., Shan, Q., Tripathy, S. K., Snyder, C. M., Xue, H. H., Griffith, T. S., Houtman, J. C. & Badovinac, V. P. (2018). Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections. PLoS pathogens, 14(10), e1007405. PMID: 30379932.

Zhang, L., Martini, G. D., Rube, H. T., Kribelbauer, J. F., Rastogi, C., FitzPatrick, V. D., Houtman, J. C., Bussemaker, H. J. & Pufall, M. A. (2018). SelexGLM differentiates androgen and glucocorticoid receptor DNA-binding preference over an extended binding site. Genome research, 28, 111-121. PMID: 29196557.

Zhang, M. S., Tran, P. M., Wolff, A. J., Tremblay, M. M., Fosdick, M. G. & Houtman, J. C. (2018). Glycerol Monolaurate (GML) induces filopodia formation by disrupting the association between LAT and SLP-76 microclusters. Science Signaling, 11, eaam9095. PMID: 29717064.

McLinden, J. H., Bhattarai, N., Stapleton, J. T., Chang, Q., Kaufman, T. M., Cassel, S. L., Sutterwala, F. S., Haim, H., Houtman, J. C. & Xiang, J. (2017). Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism. The Journal of infectious diseases, 216(9), 1164-1175. PMID: 28968905.

Bodle, C. R., Mackie, D. I., Hayes, M. P., Schamp, J. H., Miller, M. R., Henry, M. D., Doorn, J. A., Houtman JCD,, James, M. A. & Roman, D. L. (2017). Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines. Journal of natural products, 80(7), 1992-2000. PMID: 28621943.

Wallis, A. M., Wallace, E. C., Hostager, B. S., Yi, Z., Houtman JCD, & Bishop, G. A. (2017). TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22. Scientific reports, 7(1), 2081. PMID: 28522807.

Vacaflores, A., Freedman, S. N., Chapman, N. M. & Houtman, J. C. (2017). Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production. Mol Immunol, 81, 1-15. PMID: 27883938.

Zhang, M. S., Houtman, J. C. (2016). Human Serum Albumin (HSA) Suppresses the Effects of Glycerol Monolaurate (GML) on Human T Cell Activation and Function. PLoS One, 11(10), e165083. PMID: 27764189.

Hastie, J. L., Williams, K. B., Bohr, L. L., Houtman, J. C., Gakhar, L. & Ellermeier, C. D. (2016). The Anti-sigma Factor RsiV Is a Bacterial Receptor for Lysozyme: Co-crystal Structure Determination and Demonstration That Binding of Lysozyme to RsiV Is Required for sV Activation. PLoS Genet, 12(9), e1006287. PMID: 27602573.

Zhang, M. S., Sandouk, A. & Houtman, J. C. (2016). Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics. Sci Rep, 6, 30225. PMID: 27456316.

Houtman, C. J., Kitin, P., Houtman, J. C., Hammel, K. E. & Hunt, C. G. (2016). Acridine Orange Indicates Early Oxidation of Wood Cell Walls by Fungi. PLoS One, 11(7), e0159715. PMID: 27454126.

Vacaflores, A., Chapman, N. M., Harty, J. T., Richer, M. J. & Houtman, J. C. (2016). Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism. PLoS ONe, 11(6), e0157175. PMID: 27280403.

Boehm, E. M., Powers, K. T., Kondratick, C. M., Spies, M., Houtman, J. C. & Washington, M. T. (2016). The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase ? Mediates Its Interaction with the C-terminal Domain of Rev1. J Biol Chem, 291(16), 8735-44. PMID: 26903512.

Bilal, M. Y., Vacaflores, A. & Houtman, J. C. (2015). Optimization of methods for the genetic modification of human T cells. Immune Cell Biol, 93(10), 896-908. PMID: 26027856.

Bartelt, R. R., Light, J., Vacaflores, A., Butcher, A., Pandian, M., Nash, P. & Houtman, J. C. (2015). Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands. Biochim Biophys Acta, 1853(10 Pt A), 2560-9. PMID: 26079855.

Cadra, S., Gucciardi, A., Valignat, M. P., Theodoly, O., Vacaflores, A., Houtman, J. C. & Lellouch, A. C. (2015). ROZA-XL, an improved FRET based biosensor with an increased dynamic range for visualizing zeta associated protein 70 kD (ZAP-70) tyrosine kinase activity in live T cells. Biochem Biophys Res Commun, 459(3), 405-10. PMID: 25735979.

Bilal, M. Y., Zhang, E. Y., Dinkel, B., Hardy, D., Yankee, T. M. & Houtman, J. C. (2015). GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells. Cell Signal, 27(4), 841-50. PMID: 25636200.

Bilal, M. Y., Houtman, J. C. (2015). GRB2 Nucleates T Cell Receptor-Mediated LAT Clusters That Control PLC-?1 Activation and Cytokine Production. Front Immunol, 6, 141. PMID: 25870599.

Chapman, N. M., Yoder, A. N., Barbón, K. M., Bilal, M. Y., Connolly, S. F. & Houtman, J. C. (2015). Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells. J Leukoc Biol, 97(2), 285-96. PMID: 25387834.

Tremblay, M. M., Houtman, J. C. (2015). TCR-mediated functions are enhanced in activated peripheral blood T cells isolated from leucocyte reduction systems. J Immunol Methods, 416, 137-45. PMID: 25462023.

Streeter, J., Schickling, B. M., Jiang, S., Stanic, B., Thiel, W. H., Gakhar, L., Houtman, J. C. & Miller, F. J. (2014). Phosphorylation of Nox1 regulates association with NoxA1 activation domain. Circ Res, 115(11), 911-8. PMID: 25228390.

Hastie, J. L., Williams, K. B., Sepúlveda, C., Houtman, J. C., Forest, K. T. & Ellermeier, C. D. (2014). Evidence of a bacterial receptor for lysozyme: binding of lysozyme to the anti-s factor RsiV controls activation of the ecf s factor sV. PLoS Genet, 10(10), e1004643. PMID: 25275625.

Chapman, N. M., Houtman, J. C. (2014). Functions of the FAK family kinases in T cells: beyond actin cytoskeletal rearrangement. Immunol Res, 59(1-3), 23-34. PMID: 24816556.

Cruz-Orcutt, N., Vacaflores, A., Connolly, S. F., Bunnell, S. C. & Houtman, J. C. (2014). Activated PLC-?1 is catalytically induced at LAT but activated PLC-?1 is localized at both LAT- and TCR-containing complexes. Cell Signal, 26(4), 797-805. PMID: 24412752.

Tremblay, M. M., Bilal, M. Y. & Houtman, J. C. (2014). Prior TLR5 induction in human T cells results in a transient potentiation of subsequent TCR-induced cytokine production. Mol Immunol, 57(2), 161-70. PMID: 24128895.

Chapman, N. M., Connolly, S. F., Reinl, E. L. & Houtman, J. C. (2013). Focal adhesion kinase negatively regulates lck function downstream of the T cell antigen receptor. J Immunol, 191(12), 6208-21. PMID: 24227778.

Willett, J. W., Tiwari, N., Müller, S., Hummels, K. R., Houtman, J. C., Fuentes, E. J. & Kirby, J. R. (2013). Specificity residues determine binding affinity for two-component signal transduction systems. MBio, 4(6), pii: e00420-13. PMID: 24194534.

Coussens, N. P., Hayashi, R., Brown, P. H., Balagopalan, L., Balbo, A., Akpan, I., Houtman, J. C., Barr, V. A., Schuck, P., Appella, E. & Samelson, L. E. (2013). Multipoint Binding of the SLP-76 SH2 Domain to ADAP Is Critical for Oligomerization of SLP-76 Signaling Complexes in Stimulated T Cells. Mol Cell Biol, 33(21), 4140-51. PMID: 23979596.

Slupe, A. M., Merrill, R. A., Flippo, K. H., Lobas, M. A., Houtman, J. C. & Strack, S. (2013). A calcineurin docking motif (LXVP) in dynamin-related protein 1 contributes to mitochondrial fragmentation and ischemic neuronal injury. J Biol Chem, 288(17), 12353-65. PMID: 23486469.

Chapman, N. M., Bilal, M. Y., Cruz-Orcutt, N., Knudson, C., Madinaveitia, S., Light, J. & Houtman, J. C. (2013). Distinct signaling pathways regulate TLR2 co-stimulatory function in human T cells. Cell Signal, 25(3), 639-50. PMID: 23219913.

Bartelt, R. R., Houtman, J. C. (2013). The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation. Wiley Interdiscip Rev Syst Biol Med, 5(1), 101-10. PMID: 23150273.

Dutta, S., Li, Y. L., Rock, W., Houtman, J. C., Kohen, A. & Cheatum, C. M. (2012). 3-picolyl azide adenine dinucleotide as a probe of femtosecond to picosecond enzyme dynamics. J Phys Chem B, 116(1), 542-8. PMID: 22126535.

Chapman, N. M., Yoder, A. N. & Houtman, J. C. (2012). Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells. PLoS One, 7(12), e53011. PMID: 23300847.

Dutta, S., Cook, R. J., Houtman, J. C., Kohen, A. & Cheatum, C. M. (2010). Characterization of azido-NAD+ to assess its potential as a two-dimensional infrared probe of enzyme dynamics. Anal Biochem, 407(2), 241-6. PMID: 20705046.

Guseva, N. V., Fullenkamp, C. A., Naumann, P. W., Shey, M. R., Ballas, Z. K., Houtman, J. C., Forbes, C. A., Scalzo, A. A. & Heusel, J. W. (2010). Glycosylation contributes to variability in expression of murine cytomegalovirus m157 and enhances stability of interaction with the NK-cell receptor Ly49H. Eur J Immunol, 40(9), 2618-31. PMID: 20662096.

Barda-Saad, M., Shirasu, N., Pauker, M. H., Hassan, N., Perl, O., Balbo, A., Yamaguchi, H., Houtman, J. C., Appella, E., Schuck, P. & Samelson, L. E. (2010). Cooperative interactions at the SLP-76 complex are critical for actin polymerization. EMBO J, 29(14), 2315-28. PMID: 20562827.

Collins, M., Bartelt, R. R. & Houtman, J. C. (2010). T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells. Mol Immunol, 47(9), 1665-74. PMID: 20381867.

Agassandian, M., Chen, B. B., Schuster, C. C., Houtman, J. C. & Mallampalli, R. K. (2010). 14-3-3zeta escorts CCTalpha for calcium-activated nuclear import in lung epithelia. FASEB J, 24(4), 1271-83. PMID: 20007511.

Collins, M., Tremblay, M., Chapman, N., Curtiss, M., Rothman, P. B. & Houtman, J. C. (2010). The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems. J Leukoc Biol, 87(4), 691-701. PMID: 20028775.

Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S., Lin, J. X., Houtman, J. C., Desiderio, S., Renauld, J. C., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. & Pandey, A. (2010). NetPath: a public resource of curated signal transduction pathways. Genome Biol, 11(1), R3. PMID: 20067622.

Picollo, A., Malvezzi, M., Houtman, J. C. & Accardi, A. (2009). Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters. Nat Struct Mol Biol, 16(12), 1294-301. PMID: 19898476.

Cruz-Orcutt, N., Houtman, J. C. (2009). PI3 kinase function is vital for the function but not formation of LAT-mediated signaling complexes. Mol Immunol, 46(11-12), 2274-83. PMID: 19427038.

Bartelt, R. R., Cruz-Orcutt, N., Collins, M. & Houtman, J. C. (2009). Comparison of T cell receptor-induced proximal signaling and downstream functions in immortalized and primary T cells. PLoS One, 4(5), e5430. PMID: 19412549.

Wen, K. K., McKane, M., Houtman, J. C. & Rubenstein, P. (2008). Control of the ability of profilin to bind and facilitate nucleotide exchange from G-actin. J Biol Chem, 283(14), 9444-53. PMID: 18223293.

Pigge, F. C., Dighe, M. K. & Houtman, J. C. (2008). Mono-, bis-, and tris(crown ether)s assembled around 1,3,5-triaroylbenzene scaffolds. J Org Chem, 73(7), 2760-7. PMID: 18331059.

Johnston, J. W., Coussens, N. P., Allen, S., Houtman, J. C., Turner, K. H., Zaleski, A., Ramaswamy, S., Gibson, B. W. & Apicella, M. A. (2008). Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019. J Biol Chem, 283(2), 855-65. PMID: 17947229.

Houtman, J. C., Brown, P. H., Bowden, B., Yamaguchi, H., Appella, E., Samelson, L. E. & Schuck, P. (2007). Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: application to adaptor protein complexes in cell signaling. Protein Sci, 16(1), 30-42. PMID: 17192587.

Houtman, J. C., Yamaguchi, H., Barda-Saad, M., Braiman, A., Bowden, B., Appella, E., Schuck, P. & Samelson, L. E. (2006). Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1. Nat Struct Mol Biol, 13(9), 798-805. PMID: 16906159.

Houtman, J. C., Barda-Saad, M. & Samelson, L. E. (2005). Examining multiprotein signaling complexes from all angles. FEBS J, 272(21), 5426-35. PMID: 16262684.

Houtman, J. C., Houghtling, R. A., Barda-Saad, M., Toda, Y. & Samelson, L. E. (2005). Early phosphorylation kinetics of proteins involved in proximal TCR-mediated signaling pathways. J Immunol, 175(4), 2449-58. PMID: 16081816.

Houtman, J. C., Higashimoto, Y., Dimasi, N., Cho, S., Yamaguchi, H., Bowden, B., Regan, C., Malchiodi, E. L., Mariuzza, R., Schuck, P., Appella, E. & Samelson, L. E. (2004). Binding specificity of multiprotein signaling complexes is determined by both cooperative interactions and affinity preferences. Biochemistry, 43(14), 4170-8. PMID: 15065860.

Cho, S., Velikovsky, C. A., Swaminathan, C. P., Houtman, J. C., Samelson, L. E. & Mariuzza, R. A. (2004). Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads. EMBO J, 23(7), 1441-51. PMID: 15029250.

Yamaguchi, H., Houtman, J. C., Samelson, L. E. & Appella, E. (2003). Synthesis and application of large phosphopeptides from the Linker for Activation of T cells (LAT) protein. Biopolymers, 71, P503.

Houtman, J. C., Wiepz, G. J. & Bertics, P. J. (2000). The coordinate regulation of preadipocyte growth and differentiation by EGF and growth hormone. In J. M. Ntambi (Eds.) Adipocyte biology and hormone signaling. Biomedical and Health Research, IOS Press, Amsterdam, Netherlands.

Kim, S. O., Houtman, J. C., Jiang, J., Ruppert, J. M., Bertics, P. J. & Frank, S. J. (1999). Growth hormone-induced alteration in ErbB-2 phosphorylation status in 3T3-F442A fibroblasts. J Biol Chem, 274(50), 36015-24. PMID: 10585492.

Zhang, Y., Li, D., Houtman, J. C., Witiak, D. T., Seltzer, J., Bertics, P. J. & Lauhon, C. T. (1999). Design, combinatorial chemical synthesis and in vitro characterization of novel urea based gelatinase inhibitors. Bioorg Med Chem Lett, 9(19), 2823-6. PMID: 10522699.

Wiepz, G. J., Houtman, J. C., Cha, D. & Bertics, P. J. (1997). Growth hormone attenuation of epidermal growth factor-induced mitogenesis. J Cell Physiol, 173(1), 44-53. PMID: 9326448.

Lee, D., Szumlanski, C., Houtman, J. C., Honchel, R., Rojas, K., Overhauser, J., Wieben, E. D. & Weinshilboum, R. M. (1995). Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1. Drug Metab Dispos, 23(3), 398-405. PMID: 7628307.