Background and training

Jeannette hails from a small town in Connecticut, but by 18 had decided that the West Coast was more her style. As an undergraduate, she studied biology at Reed College in Portland, Oregon (yes, you can probably blame Reed for the wild hair colors and other personality quirks). Her undergraduate thesis was with Jay Mellies, where she studied virulence regulation in enteropathogenic E. coli – this sparked her long-standing interest in infectious disease. They say your first pathogen always keeps a special place in your heart…

After graduation, Jeannette worked for 2 years as a research technician with Dave Morgan at UCSF. While studying the enzymology of the yeast anaphase-promoting complex, she developed skills as a budding (wink) biochemist and structural biologist. These tools proved invaluable during her Ph.D. with Russell Vance at UC, Berkeley, where she combined her love of infectious disease and immunology with biochemistry. As a doctoral student, Jeannette investigated the mechanism of an innate immune defensive system – the NAIP/NLRC4 inflammasome – that senses and restricts cell-invasive bacterial pathogens. Her work revealed the specific inflammasome domains used to bind bacterial ligands, and how this binding activates inflammasome defense signaling. In the course of her studies, she uncovered a mechanism (multi-surface recognition of bacterial ligands) that limits the ability of pathogens to escape immune recognition. This sparked Jeannette’s interest in the tit-for-tat evolutionary arms races that play out between pathogens and their hosts.

Current research

Jeannette joined Harmit Malik’s lab in the fall of 2017 to study host-pathogen arms races in the context of mammalian innate immunity. Pathogens like bacteria and viruses would seem to have the upper hand in these arms races, as they replicate and evolve faster and with much larger population sizes than their hosts. Yet, mysteriously, the immune system largely succeeds in protecting the host! Jeannette is specifically interested in the strategies that allow hosts to “keep up” with pathogens in these arms races. Her work has focused on the antiviral protein TRIM5α, which restricts HIV and other retroviruses, though she maintains her interest in antibacterial immunity as well. Jeannette holds a Hanna Gray fellowship through HHMI, and she is committed to mentorship of future scientists, particularly those currently under-represented in biology.

Other interests

When not in the lab, you will most likely find Jeannette exploring the out-doors. She enjoys backpacking, back-country skiing, and kayaking, among other outdoor adventures. Two weeks a year you might also run into her in the deep Nevada desert, constructing and/or burning down transient art projects.

Publications

• Tenthorey, J.L., Young, C., Sodeinde, A., Emerman, M., and Malik, H.S. (2020). Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races. bioRxiv doi: 10.1101/2020.06.12.149088.
• Duxbury, Z., Wang, S., MacKenzie, C.I., Tenthorey, J.L., Zhang, X., Huh, S.U., Hu, L., Hill, L., Ngou, P.M., Ding, P., Chen, J., Ma, Y., Guoo, H., Castel, B., Moschou, P.N., Bernoux, M., Dodds, P.N., Vance, R.E., and Jones, J.D.G. (2020). Induced proximity of a TIR signaling domain on a plant-mammalian NLR chimera activates defense in plants. PNAS (accepted).
• Tenthorey, J.L., Chavez, R.A., Thompson, T.W., Deets, K.A., Vance, R.E., and Rauch, I.R. (2020). NLRC4 inflammasome activation is NLRP3- and phosphorylation-independent during infection and does not protect from melanoma. J. Exp. Med. 217. bioRxiv doi: 10.1101/765313
• Haloupek, N., Grob, P., Tenthorey, J.L., Vance, R.E., and Nogales, E. (2019). Cryo-EM studies of the NAIP-NLRC4 inflammasomes. Methods Enzymol. 625, 177-204.
• Tenthorey, J.L.*, Haloupek, N.*, Lopez-Blanco, J.R., Grob, P., Adamson, E., Hartenian, E., Lind, N., Bourgeois, N.M., Chacon, P., Nogales, E., and Vance, R.E. (2017). The structural basis of flagellin detection by NAIP5: a strategy to limit pathogen immune evasion. Science. 358, 883-93. (*These authors contributed equally.)
• Rauch, I., Deets, K.A., Ji, D.X., von Moltke, J., Tenthorey, J.L., Lee A.Y., Phillip, N.H., Ayres, J.S., Brodsky, I.E., Gronert, K., and Vance, R.E. (2017). NAIP-NLRC4 inflammasomes coordinate intestinal epithelial cell expulsion with eicosanoid and IL-18 release via activation of Caspase-1 and -8. Immunity. 46, 649-59.
• Rauch, I., Tenthorey, J.L., Nichols, R.D., Al Moussawi, K., Kang, J.J., Kang, C., Kazmierczak, B.I., and Vance, R.E. (2016). NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. J. Exp. Med. 213, 657-65.
• Girard, J.R., Tenthorey, J.L., and Morgan, D.O. (2015). An E2 accessory domain increases affinity for the anaphase-promoting complex and ensures E2 competition. J. Biol. Chem. 290, 24614-25.
• Tenthorey, J.L., Kofoed, E.M., Daugherty, M.D., Malik, H.S., and Vance, R.E. Molecular basis for specific recognition of bacterial ligands by NAIP/NLRC4 inflammasomes. (2014). Mol. Cell. 54, 17-29.
• Hewitt, S.L., Yin, B., Ji, Y., Chaumeil, J. Marszalek, K., Tenthorey, J., Salvagiotto, G., Steinel, N., Ramsey, L.B., Ghysdael, J., Farrar, M.A., Sleckman, B.P., Schatz, D.G., Busslinger, M., Bassing, C.H., and Skok, J.A. (2009). RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat. Immunol. 10, 655-64.
• Visintin, I., Feng, Z., Longton, G., Ward, D.C., Alvero, A.B., Lai, Y., Tenthorey, J., Leiser, A., Flores-Saiib, R., Yu, H., Azori, M., Rutherford, T., Schwartz, P.E., and Mor, G. (2008). Diagnostic markers for early detection of ovarian cancer. Clin Cancer Res. 14, 1065-72.