Leslie Aldrich
Associate Professor
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2230 SELW, MC 111
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About
Research in the Aldrich lab investigates complex biological phenomena using novel small-molecule probes to identify new therapeutic strategies for unmet medical needs. Our research interests span three major areas of chemical biology:
(1) Development of methods to access natural product-like scaffolds for the determination of chemical features that predict biological performance diversity.
(2) High-Throughput and High-Content Screening to identify small molecules that modulate biological pathways implicated in disease states.
(3) Exploration of cellular processes that are important in human health using newly discovered small-molecule probes, with the ultimate goal of discovering new treatments for 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. 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.
Selected Publications
Salkovski M.,* Pavlinov I.,* Gao Q., Aldrich L. N. Development of a High-Throughput, Compound-Multiplexed Fluorescence Polarization Assay to Identify ATG5-ATG16L1 Protein-Protein Interaction Inhibitors. SLAS Discov. 2021, 26, 933. DOI: 10.1177/24725552211000679
Hippman R. S., Pavlinov I., Gao Q., Mavlyanova M. K., Gerlach E. M., Aldrich L. N. Multiple Chemical Features Impact Biological Activity Diversity of a Highly Active Natural Product-Inspired Library. ChemBioChem. 2020, 21, 3137. DOI: 10.1002/cbic.202000356.
Pavlinov I., Salkovski M., Aldrich L. N. Beclin 1-ATG14L Protein-Protein Interaction Inhibitor Selectively Inhibits Autophagy through Disruption of VPS34 Complex I. J. Am. Chem. Soc. 2020, 142, 8174. DOI: 10.1021/jacs.9b12705
Gerlach E. M.,* Korkmaz M. A.,* Pavlinov I., Gao Q., Aldrich L. N. Systematic diversity-oriented synthesis of reduced flavones from γ-pyrones to probe biological performance diversity. ACS Chem. Biol. 2019, 14, 1536. DOI: 10.1021/acschembio.9b00294
Pavlinov I., Gerlach E. M., Aldrich L. N. Next generation diversity-oriented synthesis: a paradigm shift from chemical diversity to biological diversity. Org. Biomol. Chem. 2019, 17, 1608. DOI: 10.1039/c8ob02327a
Education
- 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)