- Graduate Program Chair
- Research area(s): Microbiome and Cancer
Ph.D., Biochemistry, University of South Carolina, 2007
B.S., Chemistry, Wofford College, 2002
- August 2014 – present: Assistant Professor, Department of Biochemistry, Virginia Polytechnic
Institute and State University, Blacksburg VA
- July 2011- August 2014: Research Associate, Department of Chemistry, The Scripps Research
Institute, Jupiter FL
- July 2009 – July 2011: NIH Ruth L. Kirschstein Postdoctoral Fellow, Harvard Medical School and
Massachusetts General Hospital, Department of Microbiology and Molecular Genetics/Division of
Infectious Diseases, Boston MA
BCHM 2974: Independent Study
BCHM 5974: Independent Study
BCHM 4115: General Biochemistry
BCHM 4994: Undergraduate Research
More than 15% of carcinomas can be attributed to known infectious agents such as bacteria and viruses. Fusobacterium nucleatum is a gram‐negative bacterium that is significantly overrepresented in the colonic tissue of patients with colorectal cancer. We will be working at the interface of chemistry and biology to determine the role of the microbiome in cancer using: chemical biology, x‐ray crystallography, biochemistry, molecular genetics, enzymology, and cell biology.
1) Uncovering The Role of Autotransporters In Inflammation And Cancer
Autotransporters are type V secreted proteins that can be present on the surface of bacteria, or secreted after being cleaved from the outer membrane. They are the largest family of bacteria virulence factors, and most have been characterized as adhesins and proteases. Previous studies have shown these proteins to be responsible for invoking an inflammatory response during infection. We will investigate if autotransporter adhesins and proteases could be triggering this inflammation in cancer.
2) Developing Inhibitors And Chemical Probes That Target The Protease Family Of Autotransporters
Serine and cysteine protease autotransporters are key tools that gram‐negative bacteria use for survival and infection. We will take a chemical biology approach to develop inhibitors and probes to determine if inhibiting these proteins leads to altered epithelial invasion and if this in turn leads to a decreased prevalence of Fusobacterium being associated with the progression of colorectal cancer. Simple scaffolds will be used to develop diverse libraries that can be screened and fine-tuned for specific proteins within the family.
3) Uncovering F. nucleatum Proteins That Are Upregulated During Infection In Colorectal Cancer
Bacteria upregulate numerous genes during infection, and these gene patterns can be specified for the tissue that is infected. While it is known which human genes are upregulated during infection with Fusobacterium, which genes are upregulated in the bacterium have not been studied. We will use RNA‐SEQ technology to determine the gene expression patterns during infection of cultured human colonocytes, as well as mouse models of infection. This data will provide us with a list of genes that are crucial for bacterial invasion, which may lead us to discover specific pathways that produce proteins or metabolites that elicit an inflammatory response.
Slade DJ. New Roles for Fusobacterium nucleatum in Cancer: Target the Bacteria, Host, or Both? Trends Cancer. 2020 Dec 9:S2405-8033(20)30307-1.
Udayasuryan B, Nguyen TTD, Slade DJ, Verbridge SS. Harnessing Tissue Engineering Tools to Interrogate Host-Microbiota Crosstalk in Cancer. iScience. 2020 Nov 30;23(12):101878.
Casasanta MA, Yoo CC, Udayasuryan B, Sanders BE, Umaña A, Zhang Y, Peng H, Duncan AJ, Wang Y, Li L, Verbridge SS, Slade DJ. Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration. Sci Signal. 2020 Jul 21;13(641).
Xavier JB, Young VB, Skufca J, Ginty F, Testerman T, Pearson AT, Macklin P, Mitchell A, Shmulevich I, Xie L, Caporaso JG, Crandall KA, Simone NL, Godoy-Vitorino F, Griffin TJ, Whiteson KL, Gustafson HH, Slade DJ, Schmidt TM, Walther-Antonio MRS, Korem T, Webb-Robertson BM, Styczynski MP, Johnson WE, Jobin C, Ridlon JM, Koh AY, Yu M, Kelly L, Wargo JA. The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View. Trends Cancer. 2020 Mar;6(3):192-204.
Umaña A, Sanders BE, Yoo CC, Casasanta MA, Udayasuryan B, Verbridge SS, Slade DJ. Utilizing Whole Fusobacterium Genomes To Identify, Correct, and Characterize Potential Virulence Protein Families. J Bacteriol. 2019 Nov 5;201(23).
Trunk T, Casasanta MA, Yoo CC, Slade DJ, Leo JC. Comparison of type 5d autotransporter phospholipases demonstrates a correlation between high activity and intracellular pathogenic lifestyle. Biochem J. 2019 Sep 24;476(18):2657-2676.
Casasanta MA, Slade DJ. A Vector Suite for the Overexpression and Purification of Tagged Outer Membrane, Periplasmic, and Secreted Proteins in E. coli. Methods Mol Biol. 2019;1960:123-138.
Todd SM, Settlage RE, Lahmers KK, Slade DJ. Fusobacterium Genomics Using MinION and Illumina Sequencing Enables Genome Completion and Correction. mSphere. 2018 Jul 5;3(4).
Sanders BE, Umana A, Lemkul JA, Slade DJ. FusoPortal: an Interactive Repository of Hybrid MinION-Sequenced Fusobacterium Genomes Improves Gene Identification and Characterization. mSphere. 2018 Jul 5;3(4).
Casasanta MA, Yoo CC, Smith HB, Duncan AJ, Cochrane K, Varano AC, Allen-Vercoe E, Slade DJ. A chemical and biological toolbox for Type Vd secretion: Characterization of the phospholipase A1 autotransporter FplA from Fusobacterium nucleatum. J Biol Chem. 2017 Dec 8;292(49):20240-20254.
2009-2011 - NIH Ruth L. Kirschstein Postdoctoral Fellow: Harvard Medical School and Massachusetts General Hospital, Department of Microbiology and Molecular Genetics/Division of Infectious Diseases, Boston MA
2008-2009 - NIH T32 Postdoctoral Training Grant: Harvard Medical School, Department of Microbiology and Molecular Genetics, Boston MA