2230 SELW, MC 111
Research in the Aldrich group investigates complex biological phenomena using novel small-molecule probes derived from diversity-oriented synthesis. Our research interests span three major areas of chemical biology:
- Development of methods to access synthetic “unnatural product” scaffolds that are reminiscent of biologically active natural products.
- High-Throughput and High-Content Screening to identify small molecules that modulate complex biological pathways.
- Exploration of cellular processes that are important in human health using newly discovered small-molecule probes, with the ultimate goal of discovering novel therapeutic strategies for treating diseases.
One particular pathway of interest to our lab is autophagy, an evolutionarily conserved catabolic process critical to cellular homeostasis and innate immunity in which cytosolic content is engulfed in autophagosomes and degraded in lysosomes. Chemical biology efforts in our lab investigate the role of the autophagy machinery and regulatory pathways in unconventional protein trafficking, the unfolded protein response, infection, and inflammation. Defects in autophagy have been implicated in a number of human diseases, including inflammatory diseases, infectious diseases, neurodegenerative diseases, and cancer. The small-molecule probes developed within our lab will facilitate our exploration of autophagy in the context of these highly diverse diseases.
Students and postdoctoral scholars in the Aldrich lab will investigate topics at the interface of synthetic chemistry and biology with a focus on human health and disease. The highly interdisciplinary projects in our group will enable trainees to develop expertise in synthetic organic chemistry, medicinal chemistry, biochemistry, molecular biology, microbiology, cell biology, and chemical biology.
- Aldrich L. N., Kuo S.-Y., Castoreno A. B., Goel G., Kuballa P., Rees M. G., Seashore-Ludlow B. A., Cheah J. H., Latorre I. J., Schreiber S. L, Shamji A. F., Xavier R. J. Discovery of a small-molecule probe for V-ATPase function. J. Am. Chem. Soc. 2015, 137, 5563–5568. DOI: 10.1021/jacs.5b02150
- Shaw S. Y., Tran K., Castoreno A. B., Peloquin J. M., Lassen K. G., Khor B., Aldrich L. N., Tan P. H., Graham D. B., Kuballa P., Goel G., Daly M. J., Shamji A. F., Schreiber S. L., Xavier R. J. Selective modulation of autophagy, and innate and adaptive immunity by small molecules. ACS Chem. Biol. 2013, 8, 2724.
- Aldrich L. N., Berry C. B., Bates B. S., Konkol L. C., So M. M., Lindsley C. W. Towards the total synthesis of marineosin A: Construction of the macrocyclic pyrrole and an advanced, functionalized spiroaminal model. Eur. J. Org. Chem. 2013, 20, 4215.
- Aldrich L. N., Stoops S. L., Crews B. C., Marnett L. J., Lindsley C. W. Total synthesis and biological evaluation of tambjamine K and a library of unnatural analogs. Bioorg. Med. Chem. Lett. 2010, 20, 5207.
- Aldrich L. N., Dawson E. S., Lindsley C. W. Evaluation of the biosynthetic proposal for the synthesis of marineosins A and B. Org. Lett. 2010, 12, 1048.
- Aldrich L. N., Lebois E. P., Lewis L. M., Nalywajko N. T., Niswender C. M., Weaver C.D., Conn P. J., Lindsley C. W. MAOS protocols for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines. Tetrahedron Lett. 2009, 50, 212.
- B.S. (Honors, summa cum laude) 2008, Mercer University (Advisor: Kevin Bucholtz)
- Ph.D. 2012, Vanderbilt University (Advisor: Craig Lindsley)
- Postdoctoral Fellow 2012-2015, Harvard University, The Broad Institute of MIT and Harvard (Advisor: Stuart Schreiber)