Jess Leber
Research Summary / Selected Publications
The Leber Lab studies host-pathogen interactions. There is surprisingly little known about the mechanisms used by the mammalian innate immune system to sense intracellular infection by bacteria. Once they get inside our cells, intracellular bacterial pathogens are shielded from most host detection and many of our defenses, including antibodies and Complement. Instead, we detect these bacteria with germ line-encoded host receptors that provide constant surveillance for conserved microbial ligands. There are many different varieties of intracellular pathogens -- how do we sense them all, using a limited number of receptors? What microbial molecules do they sense? What are our defenses against these bacteria? These are some of the questions we study.
We’re also extremely interested in the bacterial counter-measures. Intracellular pathogens have co-evolved with our defenses for millennia, and to survive they have had to become experts in mammalian cell biology, biochemistry, and immunology. By Darwinian necessity, the host molecules they target must be critical, conserved, and non-redundant. What do the bacteria have to teach us? How do they try to avoid detection, and manipulate or subvert our defenses?
Therefore, to better understand innate immunity, we study the intracellular bacterial pathogen Listeria monocytogenes. Utilizing genomic and biochemical approaches, combined with manipulation of both host and bacterial genetics, my laboratory is interested in providing a precise molecular description of these host-pathogen interactions. Current goals include understanding how macrophages sense Listeria monocytogenes, and identification and characterization of every Listeria monocytogenes factor necessary for survival and proliferation in the face of mammalian innate immunity. We anticipate that this work will reveal fundamental principles of innate immunity, including the recognition and defense against all intracellular bacterial pathogens.
The Leber Lab studies host-pathogen interactions. There is surprisingly little known about the mechanisms used by the mammalian innate immune system to sense intracellular infection by bacteria. Once they get inside our cells, intracellular bacterial pathogens are shielded from most host detection and many of our defenses, including antibodies and Complement. Instead, we detect these bacteria with germ line-encoded host receptors that provide constant surveillance for conserved microbial ligands. There are many different varieties of intracellular pathogens -- how do we sense them all, using a limited number of receptors? What microbial molecules do they sense? What are our defenses against these bacteria? These are some of the questions we study.
We’re also extremely interested in the bacterial counter-measures. Intracellular pathogens have co-evolved with our defenses for millennia, and to survive they have had to become experts in mammalian cell biology, biochemistry, and immunology. By Darwinian necessity, the host molecules they target must be critical, conserved, and non-redundant. What do the bacteria have to teach us? How do they try to avoid detection, and manipulate or subvert our defenses?
Therefore, to better understand innate immunity, we study the intracellular bacterial pathogen Listeria monocytogenes. Utilizing...
Zemansky, J., Kline, B., Woodward, J.J., Leber, J.H., Marquis, H., and Portnoy, D.A. (2009) Development of a mariner based transposon and identification of Listeria monocytogenes determinants, including the peptidyl-prolyl isomerase PrsA2, that contribute to its hemolytic phenotype. Journal of Bacteriology, 191 (12): 3950-64..
Leber, J.H., Crimmins, G.T., Raghavan, S., Meyer-Morse, N.P., Cox, J.S., and Portnoy, D.A. (2007) Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular Pathogen. PLoS Pathogens Jan;4(1):e6.
Scheu, S., Stetson, D.B., Reinhardt, R.L., Leber, J.H., Mohrs, M., and Locklsey, R.M. (2006) Activation of the integrated stress response during T helper cell differentiation. Nature Immunology 7 (6): 644-51.
Leber, J.H., Bernales, S., and Walter, P. (2004) IRE1-independent Gain Control of the Unfolded Protein Response. PLoS Biology Aug; 2(8):E235.
Leber, J.H.*, Rüegsegger, U.*, and Walter, P. (2001) Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell 107, 103-114. * co-first authors
Bell, SP, Mitchell, J., Leber, J., Kobayashi, R., and Stillman, B. (1995). The multi-domain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell 83, 563-568.
Zemansky, J., Kline, B., Woodward, J.J., Leber, J.H., Marquis, H., and Portnoy, D.A. (2009) Development of a mariner based transposon and identification of Listeria monocytogenes determinants, including the peptidyl-prolyl isomerase PrsA2, that contribute to its hemolytic phenotype. Journal of Bacteriology, 191 (12): 3950-64..
Leber, J.H., Crimmins, G.T., Raghavan, S., Meyer-Morse, N.P., Cox, J.S., and Portnoy, D.A. (2007) Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular Pathogen. PLoS Pathogens Jan;4(1):e6.
Scheu, S., Stetson, D.B., Reinhardt, R.L., Leber, J.H., Mohrs, M., and Locklsey, R.M. (2006) Activation of the integrated stress response during T helper cell differentiation. Nature Immunology 7 (6): 644-51.
Leber, J.H., Bernales, S., and Walter, P. (2004) IRE1-independent Gain Control of the Unfolded Protein Response. PLoS Biology Aug; 2(8):E235.
Leber, J.H.*, Rüegsegger, U.*, and Walter, P. (2001) Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell 107, 103-114. * co-first authors
