About Us

Janet McCombs, Ph.D.

Ph.D. – University of Colorado-Boulder, Biochemistry, 2010

B.S. – University of Wisconsin-Madison, Biochemistry, 2003

Research

My work involves Streptococcus pneumoniae (pneumococcus), a highly infectious pathogen that is increasingly resistant to antibiotics. Recent studies have revealed pneumococcal-encoded neuraminidases, which cleave terminal sialic acids from glycoconjugates, are important virulence factors for infection, facilitating host cell adherence, blood-brain barrier crossing, and biofilm formation. However, the precise mechanisms linking neuraminidase activity to infection remain largely unknown. My goal is to identify specific host and bacterial virulence factors utilized by pneumococcal neuraminidases to enable efficient biofilm formation and infection of the host. To do this, I am determining substrate specificity for each neuraminidase and utilizing our photocrosslinking methods to detect specific substrates of pneumococci in host cells. Identification of virulence factors is essential to discovering much-needed therapeutic targets and could provide unique insights into mammalian protein or lipid functionalities required for bacterial recognition, binding, uptake, or transcytosis.

Publications

Geng, X, Huang, C, Qin, Y, McCombs, JE, Yuan, Q, Harry, BL, Palmer, AE, Xia, N-S, and Xue, D. (2012) Hepatitis B virus X protein targets Bcl-2 proteins to increase cytosolic Ca2+, required for virus replication and cell death induction.PNAS. In press.

Parker, RB, McCombs, JE, and Kohler, JJ. (2012) Sialidase specificity determined by chemoselective modification of complex sialylated glycans. ACS Chem Biol. 7: 1509-1514

Palmer, AE, Qin, Y, Park, JG, and McCombs, JE. (2010) Design and application of genetically encoded biosensors. Trends Biotechnol 29: 144-52. Review.

Perocci, F, Gohil, VM, Girgis, HS, Bao, XR, McCombs, JE, Palmer, AE, and Mootha, VK. (2010) MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake. Nature 467:291-296.

McCombs, JE, Gibson, EA, and Palmer, AE. (2010) Using a genetically targeted sensor to investigate the role of presenilin-1 in ER Ca2+ levels and dynamics. Mol BioSys 6: 1640-1649.

McCombs, JE and Palmer, AE. (2008) Measuring calcium dynamics in living cells with genetically encodable calcium indicators, Methods, 46: 152-59. Review.

Palmer, AE, Dittmer, P, McCombs, JE. (2008) Genetically encoded sensors for calcium and zinc, in Small Animal Whole-Body Optical Imaging Based on Genetically Engineered Probes. Edited by AP Savitsky, RE Campbell, RM Hoffman. Proc. SPIE, 6868: 686807.

Jeon, WB, Aceti, DJ, Bingman, CA, Vojtik, FC, Olson, AC, Ellefson, JM, McCombs, JE, Sreenath, HK, Blommel, PG, Seder, KD, Burns, BT, Geetha, HV, Harms, AC, Sabat, G, Sussman, MR, Fox, BG, Phillips, GN, Jr. (2005) High-throughput purification and quality assurance of Arabidopsis thaliana proteins for eukaryotic structural genomics. J Struct Funct Genomics, 6:143-47.