Dr. Brogden joined the College of Dentistry in 2004. He is director of the Iowa Institute for Oral Health Research and a professor in the Department of Periodontics.
|Jul 2017-present||Interim DEO, Department of Periodontics|
|Oct 2014-Jan 2015||Interim Associate Dean for Research|
|Nov 2012-present||Director, Iowa Institute for Oral Health Research|
|2004-present||Professor, Department of Periodontics|
|2003-2004||Research Program Representative, USDA, ARS, NADC, Ames, IA|
|1999-2004||Research Leader (Department Head), Respiratory Diseases, USDA, ARS, NADC, Ames, IA|
|1999-2004||Collaborating Professor, Cellular and Molecular Pathology specialty of Veterinary Pathology, Iowa State University, Ames, IA|
|2001-2001||National Program Leader for Animal Health, National Program Staff, USD, ARS, Beltsville, MD|
|1981-1999||Microbiologist, USDA, ARS, NADC, Ames, IA|
PREDICTIVE COMPUTATIONAL SIMULATION MODELS. Programmed Death-Ligand 1 (PD-L1) has emerged as a prominent biomarker in cancer pathogenesis and immunotherapy. It is a protein on the surface of many immune and non-immune cells and serves as an ‘immune checkpoint.’ PD-L1 binds to receptor Programmed Death-1 (PD-1) to regulate immune responses among antigen presenting cells and T-cells. Unfortunately, this exact mechanism is exploited by oral cancer cells where increased expression of PD-L1 regulates both tumor signaling and adaptive immunosuppression.
Dr. Brogden is working with Cellworks Group, Inc. to assess how patient oral cancer tumor cell genomics influences cell signaling with downstream effects on the expression of PD-L1, chemokines, and immunosuppressive biomarkers and how these profiles can be predicted and used to identify patients who would respond to PD-1 and PD-L1 immunotherapies. With Cellworks Group, Inc., he is using computational simulation models annotated with patient tumor deleterious gene mutational profiles to predict PD-L1 responses. This would facilitate selection of immunotherapies based on an individual’s patient genetic profiles. Key publications include:
- Harvey LE, Kohlgraf KG, Mehalick LA, Raina M, Recker EN, Radhakrishnan S, Prasad SA, Vidva R, Progulske-Fox A, Cavanaugh JE, Vali S, Brogden KA. Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus. Sci Rep. 2013;3:1232. PubMed PMID: 23390582; PubMed Central PMCID: PMC3565171.
- Borgwardt DS, Martin AD, Van Hemert JR, Yang J, Fischer CL, Recker EN, Nair PR, Vidva R, Chandrashekaraiah S, Progulske-Fox A, Drake D, Cavanaugh JE, Vali S, Zhang Y, Brogden KA. Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses. Sci Rep. 2014 Jan 29;4:3904. PubMed PMID: 24473528; PubMed Central PMCID: PMC3912440.
- Lanzel EA, Paula Gomez Hernandez M, Bates AM, Treinen CN, Starman EE, Fischer CL, Parashar D, Guthmiller JM, Johnson GK, Abbasi T, Vali S, Brogden KA. Predicting PD-L1 expression on human cancer cells using next-generation sequencing information in computational simulation models. Cancer Immunol Immunother. 2016 Dec;65(12):1511-1522. PubMed PMID: 27688163.
- Brogden KA., Vali S, Abbasi T. PD-L1 is a diverse molecule regulating both tumor-intrinsic signaling and adaptive immunosuppression. Translational Cancer Research 5(Suppl 7):S1396-S1399, 2016. PubMed PMID: 27688163
- Bates, A. M., Lanzel, E., Qian, F., Abbasi, T., Vali, S., and Brogden, K. A. Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC - a computational study. Oral Surg Oral Med Oral Pathol Oral Radiol (accepted for publication, May 9, 2017).
ANTIMICROBIAL PEPTIDES. Dr. Brogden helped to establish that small anionic and cationic peptides from animals and humans were antimicrobial against a variety of gram-positive bacteria, gram-negative bacteria, and fungi from animals and humans. He also helped establish that antimicrobial peptides important roles in innate immunity and serve to regulate cytokine signaling. Key publications include:
- Brogden, K. A., DeLucca II, A. J., Bland, J., and Elliott, S. Isolation of an ovine pulmonary surfactant-associated anionic peptide bactericidal for Pasteurella haemolytica. Proc Natl Acad Sci USA. 93:412-416, 1996.
- Brogden, K. A., Ackermann, M., McCray, P. B. and Tack, B. F. Antimicrobial peptides in animals and their role in host defences. Int J Antimicrob Agents 22:465-478, 2003.
- Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol. 2005 Mar;3(3):238-50. PubMed PMID: 15703760.
- This paper was identified as a Fast Breaking Paper by Essential Science IndicatorsSM as a highly cited paper. This paper was included in the joint Nature Biotechnology and Nature Reviews Drug Discovery FOCUS on antibacterials (http://www.nature.com/focus/antibacterials/library/index.html). Brogden was invited to provide comments (http://esi-topics.com/fbp/fbp-august2006.html).
- Brogden, N. K. and Brogden, K. A. Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals? Int J Antimicrob Agents. 38(3):217-25. 2011. PMID:21733662.
- Brogden, K. A., Johnson, G. K., Vincent, S. D., Abbasi, T., Vali, S. Oral inflammation, a role for antimicrobial peptide modulation of cytokine and chemokine responses. Expert Rev Anti Infect Ther. 11(10):1097-1113, 2013. PMID: 24124799.
Barwacz, C. A., Brogden, K. A., Stanford, C. M., Dawson, D. V., Recker, E. N., and Blanchette, D. Comparison of pro-inflammatory cytokines and bone metabolism mediators around titanium and zirconia dental implant abutments following a minimum of 6 months of clinical function. Clin Oral Implants Res. 26(4):e35-41, 2015. PMID:24417614.
Recker, E. N., Avila-Ortiz, G., Fischer, C. L., Pagan-Rivera, K., Brogden, K. A., Dawson, D. V., and Elangovan, S. A Cross-sectional Assessment of Biomarker Levels around Implants Versus Natural Teeth in Periodontal Maintenance Patients. J Periodontol. 86(2):264-272, 2015. PMID:25269523.
Poulsen, C., Mehalick, L. A., Fischer, C. L., Lanzel, E. A., Bates, A. M., Walters, K. S., Cavanaugh, J. E., Guthmiller, J. M., Johnson, G. K., Wertz, P. W., and Brogden, K. A. Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. Toxicol Lett. 237(1):21-29, 2015. PMID:26005054.
Kinn, P. M., Holdren, G.O., Westermeyer, B. A., Abuissa, M., Fischer, C. L., Fairley, J. A., Brogden, K. A., and Brogden, N. K. Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin. Sci. Rep. 5;10472, 2015. PMID:26035055.
Recker, E. N., Brogden, K. A., Avila-Ortiz, G., Fischer, C. L., Pagan-Rivera, K., Dawson, D. V., Smith, K. M., Elangovan, S. Novel biomarkers of periodontitis and/or obesity in saliva-an exploratory analysis. Arch Oral Biol. 60(10):1503-1509. PMID:26263539.
Leelakanok, N., Fischer, C. L., Bates, A. M., Guthmiller, J. M., Johnson, G. K., Salem, A. K., Brogden, K. A., and Brogden, N. K. Cytotoxicity of HBD3 for dendritic cells, normal human epidermal keratinocytes, hTERT keratinocytes, and primary oral gingival epithelial keratinocytes in cell culture conditions. Toxicol Lett. 239(2):90-96, 2015. PMID:26367466.
Mehalick, L. A., Poulsen, C., Fischer, C. L., Lanzel, E. A., Bates, A. M., Walters, K. S., Cavanaugh, J. E., Guthmiller, J. M., Johnson, G. K., Wertz, P. W., and Brogden, K. A. Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. Data-In-Brief 5:285-291, 2015. PMID:26550599.
Fischer, C. L., Dawson, D. V., Blanchette, D. R., Drake, D. R., Wertz, P. W., and Brogden, K. A. Protein analysis of sapienic acid-treated Porphyromonas gingivalis suggests differential regulation of multiple metabolic pathways. J Bacteriol. 198:157-167, 2015. PMID:26483519.
Lanzel, E. A., Gomez Hernandez, M. P., Bates, A. M., Treinen, C. N., Starman, E. E., Fischer, C. L., Parasher, Guthmiller, J. M., Johnson, G. K., D., Abbasi, T., Vali, S., and Brogden, K. A. Predicting PD-L1 expression on cancer cells using next-generation sequencing (NGS) information in computational simulation models. Cancer Immunol Immunother 65(12):1511-1522, 2016. PMID:27688163.
Garaicoa Pazmino, J. L., Bates, A. M., Fischer, C. L., Guthmiller, J. M., Gustavo, A. O., Johnson, G. K., Stanford, C., and Brogden, K. A. Minimal inhibitory concentration of antimicrobial and antifungal agents in denture adhesive material against Candida albicans. J Prosthodontics. J Prosthodont. doi: 10.1111/jopr.12565. Epub ahead of print, 2016. PMID: 27870138.
Li, K., Wohlford-Lenane, C. L., Channappanavar, R., Park, J. E., Earnest, J. T., Bair, T. B., Bates, A. M., Brogden, K. A., Flaherty, H. A., Gallagher, T., Meyerholz, D. K., Perlman, S., McCray, P. B., Jr. Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice. Proc Natl Acad Sci U S A. 114(15):E3119-E3128, 2017.
Bates, A. M., Garaicoa, J. L., Fischer, C. L., and Brogden, K. A. Diminished Antimicrobial Peptide and Antifungal Antibiotic Activities against Candida albicans in Denture Adhesive. Antibiotics 10.3390/antibiotics6010006, 2017. PMID: 28178179
Bates, A. M., Lanzel, E., Qian, F., Abbasi, T., Vali, S., and Brogden, K. A. Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC - a computational study. Oral Surg Oral Med Oral Pathol Oral Radiol (TRIPLEO-D-17-00036R1, accepted for publication, May 9, 2017).
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Dr. Brogden is a member of the American Society for Microbiology, a Fellow in the American Academy of Microbiology, and a member of Phi Zeta and the American Association for the Advancement of Science. He is on the Board of Scientific Reviewers for the Annals of Agricultural and Environmental Medicine (1992-present) and was on the Board for Infection and Immunity (1998-2000). He has co-edited three books: Virulence Mechanisms of Bacterial Pathogens, second and third editions (ASM Press, Washington, D.C.,1995 and 2000) and Polymicrobial Diseases (ASM Press, Washington, D.C., 2002).