Assistant Research ProfessorOffice: MonTEC, 1121 E Broadway, Suite 121
Ph.D., Biomedical Sciences - Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Collge of Medicine, Rochester, MN, 2011
B.S., Molecular Biology, B.S., Chemistry, University of Wyoming, Laramie, WY, 2002
Innate Immune modulation and Cancer Immunotherapy
Our lab is interested in investigating and developing novel innate immune modulating compounds for the treatment of various infectious diseases and other therapeutic targets. We have a particular interest and extensive history in the invesitgation and development of novel TLR4 and TLR7/8 agonists (and antagonists) for use as vaccine adjuvants and for non-specific immunity.
My primary focus currently is our work on the identification of novel C Type Lectin Receptor (CLR) agonists for use as adjuvants to induce antigen-specific Th17 immunity against bacterial and fungal pathogens including Mycobacterium tuberculosis (Mtb), Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Alpergillus fumigatus and others. This work includes collaborations with several other groups on campus to synthesize, Dr. Kendal Ryter, and formulate, Dr. David Burkhart, libraries of novel, synthetic trehalose-derivatives and analyze their immune-stimulating activity. This work includes in depth studies into the CLR Mincle and its role in shaping a downstream adaptive immune response induced by these structurally variant molecules.
In addition to my work with innate immune agonists as vaccine adjuvants, I am also interested in and pursuing the use of several of these novel molecules as adjuvants for cancer immunotherapy. This work will dissect the underlying mechanism of their action in these malignancies.
Field of Study
Molecular Pharmacology and Experimental Therapeutics
Smith AJ, Li Y, Bazin-Lee H, St-Jean JR, Larocque D, Baldridge J. Evaluation of novel synthetic TLR7/8 agonists as human vaccine adjuvants. Submitted to Vaccine, in Review (2016)
Secreto FJ, Li X, Bruinsma E, Perales-Clemente E, Hrstka SC, Smith AJ, Hawse G, Oommen S, Wigle D, Nelson TJ. An Effective, Cost Efficient Means of Assessing hiPSC Pluripotency: Quantifying the Cellular Response to DNA Damage. Submitted to Nature Communications. August 2015.
Smith AJ, Nelson N, Oommen S, Hartjes K, Folms C, Terzic A, Nelson TJ. Apoptotic Susceptibility to DNA Damage of Pluripotent Stem Cells Facilitates Pharmacologic Purging of Teratoma Risk. Stem Cells Transl Med. 2012 Oct;1(10):709-18. PMID: 23197662
Pang Y-P, Dai H, Smith AJ, Meng XW, Schneider PA, Kaufmann SH. Bak Conformational Changes Induced by Ligand Binding: Insight into BH3 Domain Binding and Bak Homo-Oligomerization. Scientific Reports. 2012; 2(257). PMID: 22355769
Dai H, Smith AJ, Meng XW, Schneider PA, Pang YP, Kaufmann SH. Transient binding of an activator BH3 domain to the Bak BH3-binding groove initiates Bak oligomerization. Journal of Cell Biology. 2011; 194:39-48. PMID: 21727192
Smith AJ, Dai H, Correia C, Takahashi R, Lee SH, Schmitz I, Kaufmann SH. Noxa/Bcl-2 interactions contribute to bortezomib resistance in human lymphoid cells. Journal of Biological Chemistry. 2011; 20:17682-92. PMID: 21454712
Motriuk-Smith D, Smith AJ, Hayashi CY, Lewis RV. Analysis of the conserved N-terminal domains in major ampullate spider silk proteins. Biomacromolecules. 2005; 6:3152-9. PMID: 16283740
• Immune assays and development: primary human immune cell culture (dendritic cells and T cells) and assay development, cell culture reporter systems (SEAP/luciferase), cytokine ELISA/Luminex, DC:T cell co-culture and CFSE dilution/MHC tetramer staining
• Molecular biology: transfection (lipid and electroporation)/viral transduction, cloning, site-directed mutagenesis, recombinant protein expression and purification, western, southern and northern blotting, immunoprecipitation, RNA/DNA extraction, qRT-PCR/PCR (single and array), sequencing, siRNA, SPR/Biacore, antibody production
• Cellular biology: extensive and varied mammalian cell culture experience, multi-color flow cytometry/FACS and intracellular staining, IHC/microscopy, stable cell line development, cytotoxicity and proliferation assays (Annexin-V staining, MTT, etc.)