MICaB Graduate Program
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Tanya S. Freedman, Ph.D.
Tyrosine kinase signaling and macrophage regulation
Immune cells are tuned exquisitely to identify pathogens and avoid hypersensitivity. In macrophages the Src-family tyrosine kinases (LynA, LynB, Hck, and Fgr) regulate a size sensing mechanism based on their ability to nucleate ITAM receptor clusters. Bacteria and yeast cells are a few microns in diameter, and resulting micron-sized ITAM clusters trigger strong antimicrobial signaling. We are studying how regulation of the Src-family kinases, especially LynA, regulate the receptor-ligand size threshold that sometimes results in macrophage hypersensitivity to smaller stimuli. We are also interested in how LynA and other signaling proteins contribute to macrophage roles in autoinflammation, tumor growth, and antimicrobial responses.
Selected Recent Publications:
- Freedman TS*, Tan YX, Skrzypczynska KM, Manz BN, Sjaastad FV, Goodridge HS, Lowell CA, Weiss A*. (2015) "LynA regulates an inflammation-sensitive signaling checkpoint in macrophages" eLife 4:e09183 (*Corresponding)
- Tan YX, Manz BN, Freedman TS, Killeen N, Zhang C, Shokat K, Weiss A. (2014) "Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling" Nat Immunol 15(2):186-194.
- Limnander A, Depeille P, Freedman TS, Liou J, Leitges M, Kurosaki T, Roose JP, Weiss A. (2011) "STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development" Nat Immunol 12(5):425-33.
- Wang H, Kadlecek TA, Au-Yeung BB, Goodfellow HE, Hsu LY, Freedman TS, Weiss A.(2010) "ZAP-70: an essential kinase in T-cell signaling" Cold Spring Harb Perspect Biol. 2(5):a002279.
- Freedman TS, Sondermann H, Kuchment O, Friedland GD, Kortemme T, Kuriyan J. (2009) "Differences in flexibility underlie functional differences in the Ras activators son of sevenless and Ras guanine nucleotide releasing factor 1" Structure 17(1): 41-53.
- Freedman TS, Sondermann H, Friedland GD, Kortemme T, Bar-Sagi D, Marqusee S, Kuriyan J. (2006) "A Ras-induced conformational switch in the Ras activator Son of sevenless" Proc Natl Acad Sci USA 103(45): 16692-16697.