Kim A. Brogden

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:

1. 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.
2. 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.
3. 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.
4. 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
5. 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:

1. 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.
2. 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.
3. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol. 2005 Mar;3(3):238-50. PubMed PMID: 15703760.
4. 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).
4. 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.
5. 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.