个人简介

2014-present Huisking Foundation, Inc. Assistant Professor, University of Notre Dame 2009-2014 Walther Cancer Assistant Professor, University of Notre Dame 2005-2009 Postdoctoral Fellow, National Cancer Institute 2004-2005 Postdoctoral Research Associate, University of Illinois at Urbana-Champaign 2004 Ph.D. Chemistry, University of Illinois at Urbana-Champaign 1999 A.B. in Chemistry, Cornell University Award: 2014 NSF Early CAREER Award 2011 Young Investigator Award, Spectroscopy Society of Pittsburgh 2007 WCIR Brigid G. Leventhal Scholar In Cancer Research Award 2005-2009 Sallie Rosen Kaplan Postdoctoral Fellowship, National Cancer Institute

研究领域

Biochemistry

Cancer arises from insults to the genome. With genomic damage, the expression levels of genes are altered from their normal state. Changes in the genome, transcriptome and proteome have been found to be highly conserved among samples from adenomas to carcinomas to metastases. Because genetic changes are commonly repeated among cancer patients, a better understanding of which genes, transcripts, and proteins are affected could have broad health implications. Therefore, the best way to understand the molecular underpinnings of cancer is to dissect the deregulated pathways that are contributing to the cancer phenotype, identify the aberrantly expressed genes and their products, and decipher their effect on downstream targets. The Hummon Research Group develops high-throughput methods to evaluate the proteome in cancer cells. On-going projects include: • Interrogating the distribution of analytes in three-dimensional cell cultures using imaging mass spectrometry Three dimensional cell cultures are popular model systems in health-related biological research. They combine the flexibility of cell culture with structural information not possible with standard two-dimensional cultures. Our research group is developing mass spectrometric tools to enable the characterization of three-dimensional cell culture systems. We are the first research group to examine three dimensional cell culture systems via imaging mass spectrometry. We are developing approaches to manipulate 3D cultures and prepare them for imaging. We are working with colon adenocarcinoma cell lines, which form 3D structures called spheroids. In our mass spectrometric images, we detect changes in the spatial distribution of proteins throughout the spheroid structures. We are expanding our studies to genetically manipulated 3D cultures to explore molecular changes associated with the beginning of metastasis and the epithelial to mesenchymal transition. To examine the changes in protein expression and distribution that accompany this transition, we are growing cultures containing inducible shRNAs that silence a critical regulatory gene, E-Cadherin. We will map the alterations in protein expression that accompany silencing of E-Cadherin on the protein level. Finally, we are applying our approach to examine drug concentrations and penetration depth into 3D cultures. • Investigating the impact that individual and clusters of miRNAs have on the cancer proteome and transcriptome. We investigated the effect that the miR-143/145 cluster has on the transcriptome and proteome of colorectal cancer. Expression of the miR-143/-145 cluster is reduced in colon cancer. As the deregulation of the miR-143/145 cluster is implicated in tumorigenesis, we combined SILAC and microarray analyses to systematically interrogate the impact of miR-143/145 on the colon cancer proteome and transcriptome. Our results indicate that the summed effects of individually introduced microRNAs produce distinct molecular changes from the consequences of the assembled cluster. This finding has broad implications to additional clusters in a number of disease states and cellular processes. We conclude that there is a need to investigate both the individual and combined functional implications of a microRNA cluster. We are expanding our studies to the miR-23a~27a~24-2 cluster. • Examining changes to the phosphoproteome that accompany cancer progression. We are investigating alterations in the phosphoproteome that occur at two critical points in cancer progression. First, we are examining the changes in the phosphoproteome that occur with exposure to very low doses of ionizing radiation, which can lead to tumorigenesis. We are also comparing changes in the abundance of phosphoproteins in primary versus metastatic colon cancer cells. To conduct this research, we have developed a phosphoproteomic enrichment strategy that greatly advances the number of phosphoproteins identified in a complex biological sample. • Exploring changes to the proteome following RNA interference-based reduction of the expression of pivotal regulatory genes We are using loss-of-function analysis via RNA interference to investigate the role of specific genes in colorectal cancer. For example, we are examining the changes to the transcriptome and proteome following the reduction of the gene FLASH. Knockdown of FLASH has been shown to drastically reduce the viability of colon cancer cells. We have also investigated the distinct gene expression patterns on the right and left side of the colon and their relationship to relapse. In particular, expression of the genes CDX2 and NOX4 are strong predictors of survival. We are further exploring the functional role of NOX4 with in vitro loss-of-function studies. •Developing novel sample preparation strategies for proteomic analysis As a complement to our mechanistic studies, we are also developing proteomic sample preparation protocols. We have devised an improved method for phosphopeptide enrichment. We are also developing a novel method to selectively enrich and isolate peptides from archived tissue samples embedded in optimal cutting temperature (OCT) compound. Many primary biobanked tissue samples are embedded in OCT, a substance that interferes with mass spectrometric analysis. Successful analysis of these bio-banked tissue samples would be an important resource in understanding cancer.

近期论文

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Weaver EM, Hummon AB, Keithley RB. "Chemometric Analysis of MALDI Mass Spectrometric Images of Three-Dimensional Cell Culture Systems". Analytical Methods. 2015. In Press. •Feist P, and Hummon AB "Proteomic Challenges: Sample Preparation Techniques for Microgram-Quantity Protein Analysis from Biological Samples". International Journal of Molecular Sciences. 2015. In Press. •Feist P, Sun L, Liu X, Dovichi NJ, Hummon AB. "Bottom-up proteomic analysis of single HCT 116 colon carcinoma multicellular spheroids". Rapid Communications in Mass Spectrometry. 2015. In Press. •Liu X, Hummon AB. "Quantitative Determination of Irinotecan and the Metabolite SN-38 by nLC-ESI-MS/MS in Different Regions of Multicellular Tumor Spheroids". Journal of The American Society for Spectrometry. In Press. •Bauer KM, Watts T, Buechler S, Hummon AB. "Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3". Journal of Proteome Research. 2014 Nov 7; 13 (11);4910-8. •Ahlf DR, Masyuko RN, Hummon AB, Bohn PW. "Correlated Mass Spectrometry Imaging and Confocal Raman Microscopy for Studies of Three-Dimensional Cell Culture Sections". Analyst. 2014 Sep 21;139 (18);4578-85. Wheatcraft Ahlf DR, Liu X, Hummon AB. "Sample Preparation Strategies for Mass Spectrometry Imaging of 3D Cell Culture Models". Journal of Visualized Experiments. 2014 Dec 5;(94). Weston LA, Bauer KM, Skube SB, Hummon AB. "Selective, bead-based global peptide capture using a bifunctional crosslinker". Anal Chem. 2013 Nov 19;85(22):10675-9. Weston LA, Hummon AB. "Comparative LC-MS/MS analysis of Optimal Cutting Temperature (OCT) compound removal for the study of mammalian proteomes". Analyst. 2013 Nov 7;138(21):6380-4. •Keithley RB, Weaver EM, Metzinger MP, Rosado AM, Hummon AB, Dovichi NJ. "Single Cell Metabolic Profiling of Tumor Mimics." Anal Chem. 2013 Oct 1;85(19);8910-8. Yue XS, Hummon AB. "Combination of Multi-Step IMAC Enrichment with High-pH Reverse Phase Separation for In-Depth Phosphoproteomic Profiling". Journal of Proteome Research. 2013 Sep 6;12(9):4176-86. Weston LA*, Bauer KM*, Hummon AB. "Comparison of bottom-up proteomic approaches for LC-MS analysis of complex proteomes". Analytical Methods, 2013, 5 (18), 4615 - 4621. Liu, X, Weaver EM, Hummon AB."Evaluation of Therapeutics in Three-Dimensional Cell Culture Systems by MALDI Imaging Mass Spectrometry". Analytical Chemistry, 2013 Jul 2;85(13):6295-302. Epub 2013 Jun 11. •Hummon, A.B.; Dovichi, N.J. "The Tools of Proteomics" The Analytical Scientist, 2013, 1, 413-420. •Dovichi NJ, Hummon AB. "The Tools Behind Genomics" The Analytical Scientist, 2013, 1, 24-31. Weaver EM, Hummon AB. "Imaging mass spectrometry: from tissue sections to cell cultures" Advanced Drug Discovery Reviews, 2013 Jul;65(8):1039-55. Yue XS, Hummon AB. "Mass spectrometry-based phosphoproteomics in cancer research." Front. Biol. 2012, 7(6): 566–586. •Bauer KM, Hummon AB. "Effects of the miR-143/-145 MicroRNA Cluster on the Colon Cancer Proteome and Transcriptome." J Proteome Res. 2012 Sep 7;11(9):4744-54. •Bauer KM, Lambert PA, and Hummon AB. "Comparative label-free LC-MS/MS analysis of colorectal adenocarcinoma and metastatic cells treated with 5-fluorouracil" Proteomics 2012 Jun;12(12):1928-37. •Hummon AB, Pitt JJ, Camps J, Emons G, Skube SB, Huppi K, Jones TL, Beissbarth T, Kramer F, Grade M, Difilippantonio MJ, Ried T and Caplen NJ. "Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells" Molecular Cancer 2012 Jan 4;11:1.