Abram J. (Bram) Axelrod
Ph.D., 2012, University of Texas at Austin
M.A., 2005, State University of New York at Buffalo
B.A., 2003, Brandeis University
Our research is focused on the synthesis of complex glycoproteins, natural products, and oligosaccharides of importance in immuno-oncology and infectious diseases. The projects we investigate are chosen based on the complexity and broader applicability of the chemistry involved, its ability to interrogate a significant biological problem, and the greater implications for translational research. This begins with the development of novel synthetic methods or tactics making difficult chemistry accessible, accelerating biological investigation and discovery, especially in the context of material unreachable through isolation or expression-based methods, Ideally, in direct collaboration with biologists and clinicians, this will lead to the identification of lead structures as pharmacological tools and potential therapeutics.
Glycoproteins, often referred to as 'biologics', are now an established class of therapeutic macromolecules in medicine. Our laboratory is actively involved in developing new amide bond-forming reactions applied to the synthesis of single isoform glycoproteins. Representative projects include the design of ovarian cancer-related epitopes utilized in 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.
With regard to natural products, their structural complexity can limit timely pharmacological investigation and therapeutic development, as synthesis or derivatization becomes a bottleneck for investigation. We are pursuing the synthesis of small molecules with novel mechanisms of action against pancreatic and lung cancers. By developing concise platforms to structurally-complex molecules we can enable rapid investigation and potential development as chemotherapeutics. Importantly, these approaches will be able to produce edited structures for identifying structure-activity relationships and will incorporate radiolabeled probes for imaging purposes.
Oligosaccharides mediate complex signaling events in the body, and demonstrate manifold biological activities. We are investigating the synthesis of unusual glycans to stimulate the immune system against invading pathogens and to invigorate stalled immune responses in the context of oncology. Specifically, we will apply these carbohydrate molecules toward activating natural killer (NK) cells and T cells. These projects reside on the interface of organic chemistry and chemical biology and are opportunities for organic chemistry to drive innovation in medicine and immunology.
Honors and Credentials
- Memorial Sloan Kettering Teaching Fellow, 2013
- Hamilton-Schoch Fellow, 2007 - 2008