Abram Axelrod

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Our current research interests are concerned with the preparation of molecules relevant to immunology and oncology, and using them as tools in medicinal chemistry and pharmacology. Often referred to as 'biologics’, glycoproteins are now an established class of therapeutic macromolecules utilized in medicine. Our laboratory is actively involved in the synthesis of single isoform, glycosylated peptides. Representative projects include the design of ovarian cancer-related epitopes utilized for antibody generation against aggressive tumors, the synthesis of hybrid diabodies capable of macrophage reprogramming in both cancer and autoimmune diseases, and preparing disease-specific targeted FOXO transcription factors as new types of therapeutics. As an extension of our interest in the synthesis and chemical biology of glycoproteins, we are focusing on developing new catalytic amide bond-forming reactions as part of this program. Oligosaccharides mediate complex signaling events in the body, and demonstrate manifold biological activities. We are investigating the synthesis of unusual carbohydrate constructs with potential to invigorate stalled immune responses in individuals with chronic infections and cancer. We are specifically focusing on the activation of dendritic cells, natural killer (NK) cells, and T cells though auxiliary stimulation mechanisms, independent of major receptor-induced activation. By developing concise platforms to biologically active, structurally-complex natural products, we can enable more rapid investigation into their pharmacology and potential therapeutic development. Our laboratory is pursuing the synthesis of both immunomodulatory and anti-cancer molecules possessing novel mechanisms of action, with an emphasis on pancreatic and lung cancers. Importantly, our approaches to these natural products will be able to produce edited analogues for identifying structure-activity relationships and be capable of incorporating radiolabeled probes for imaging and diagnostic purposes.

Selected Publications:

Brailsford, J.A.*; Stockdill, J.L.*; Axelrod, A.J.*#; Peterson, M.T.; Vadola, P.A.; Johnston, E.V.; Danishefsky, S.J. Total Chemical Synthesis of the b-Subunit of Thyroid Stimulating Hormone Enabled by Arginine Tagged Acetamidomethyl Solubilizing Groups. Tetrahedron, 2018, 74, 1951-1956.

Eliasen, A.M.; Chin, M.R.; Axelrod, A.J.; Abagyan, R.; Siegel, D. Cascade Reactions Leading to the Mechanism of Action of Vinaxanthone and Xanthofulvin, Natural Products that Drive Nerve Repair. Tetrahedron, 2018, 74, 3238-3245.

Rao, T.D.*; Fernandez-Tejada, A.* Axelrod, A.*; Rosales, N.; Yan, X.; Thapi, S.; Wang, A.; Park, K.J.; Nemieboka, B.; Xiang, J.; Lewis, J.S.; Overa, N.; Levine, D.A.; Dnaishefsky, S.J.; Spriggs, D. Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth ACS Chemical Biology, 2017, 12, 2085-2096.

Axelrod, A.; Eliasen, A.M.; Chin, M.R.; Zlotkowski, K.; Siegel, D. Syntheses of Xanthofulvin and Vinaxanthone, Natural Products Enabling Spinal Cord Regeneration. Angew. Chem. Int. Ed. Int. Eng., 2013, 52, 3421-3424

* denotes co-first author. # = corresponding author.