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Dr. Jakob von Moltke
Jakob von Moltke, Ph.D.
Assistant Professor, Department of Immunology
Dr. von Moltke graduated with a Bachelor’s degree in Genetics, Cell and Developmental Biology from Dartmouth College in New Hampshire. He went on to receive his Masters of Arts in Biotechnology in 2007 from Columbia University and his Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. He completed his postdoctoral training in the Locksley lab at the University of California, San Francisco, and joined the University of Washington Department of Immunology as an Assistant Professor in 2016.
Department of Immunology
The Moltke lab studies immune responses to parasitic worms (helminths) and allergens. These responses, collectively known as type 2 immunity, are triggered by an astonishing diversity of agonists, from macroscopic live worms to microscopic inert particles to soluble enzymes. How do these all look the same to the mammalian immune system? To answer this question, we focus on the initiation of type 2 immunity, when the immune system first encounters a disturbance and must decide how to respond. Using laboratory mice and the helminths Nippostrongylus brasiliensis and Heligmosomoides polygyrus as model organisms, our goal is to provide insights that will lead to improved treatment and prevention of asthma, allergy, and other type 2 inflammatory conditions.
Among the first cells activated during a type 2 response are the group 2 innate lymphoid cells (ILC2s). ILC2s serve as the predominant early source of the cytokines that together give rise to many of the hallmarks of type 2 immunity, such as eosinophilia, increased mucus production, hypercontractility of smooth muscle, and tissue remodeling. Importantly, ILC2s cannot directly sense the presence of type 2 agonists (worms, allergens, etc.) and are instead activated by signals from their surrounding tissue. The identity, source, and regulation of these ILC2-activating signals are the current focus of projects in the lab.
We are particularly interested in specialized epithelial cells called tuft cells. Although they were discovered more than 50 years ago, the function of tuft cells remained unclear. Recently, we and others demonstrated that tuft cells are the exclusive source of the ILC2-activating cytokine IL-25 in the intestine. During worm infection, a feed forward loop comprised of tuft cells, ILC2s, and the epithelial stem cell compartment leads to dramatic epithelial remodeling, and without tuft cell-derived IL-25, worm clearance is delayed. We are currently investigating how else tuft cells contribute to the type 2 immune response.
von Moltke J, Ji M, Liang H-E, Locksley RM (2016). Tuft cell-derived IL-25 regulates an intestinal ILC2 – epithelial response circuit. Nature 529:221-5
von Moltke J and Locksley RM (2014). I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis. Current Opinions in Immunology 31:58-65
Nussbaum JC, Van Dyken SJ, von Moltke J, Cheng LE, Mohapatra A, Molofsky AB, Thornton EE, Krummel MF, Chawla A, Liang H-E, Locksley RM (2013) Type II innate lymphoid cells control eosinophil homeostasis. Nature 502:245-248
von Moltke J, Ayres JS, Kofoed EM, Chavarría-Smith J, Vance RE (2012) Recognition of Bacteria by Inflammasomes. Annu Rev Immunol 31:73-106
von Moltke J, Moayeri M, Trinidad NJ, Kintzer AF, Wang SB, van Rooijen N, Krantz BA, Leppla SH, Gronert K, Vance RE. (2012) Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature 490: 107-11.
Sauer JD, Sotelo-Troha K, von Moltke J, Monroe KM, Rae CS, et al. (2011) The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential function of Sting in the in vivo interferon response to Listeria monocytogenes and cyclic dinucleotides. Infect Immun 79: 688-694.
Broz P*, von Moltke J*, Jones JW, Vance RE, Monack DM (2010) Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe 8: 471-483.
Lightfield KL, Persson J, Brubaker SW, Witte CE, von Moltke J, et al. (2008) Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nat Immunol 9: 1171-1178.
B.A., Biology, Dartmouth College
M.A., Biotechnology, Columbia University
Ph.D., Molecular & Cell Biology, UC Berkeley
James Jaffe, email@example.com