Positions

Overview

  • Introduction:

    I received a BS in Chemistry from the University of Virginia in 1977 and a PhD from Duke University in 1985. While a student at Duke University under Dr. Barbara Shaw in Chemistry and Dr. David Sedwick in the Department of Medicine, I obtained a diverse education in experimental design and basic research covering topics from cell culture, protein isolation and gel electrophoresis to organic synthesis and drug design. After a brief postdoctoral fellowship at NIEHS in the Research Triangle Park with Dr. Robert London in the area of deuterated probe development for in vivo NMR metabolism, I began a 25-year career in drug design and synthesis at Southern Research Institute in Birmingham, Alabama, advancing to the position of Director of Drug Discovery Technology. Although involved in numerous diverse programs from chemical education and outreach, optimization of Bath and Body Works bubble baths, chemical and biological diversity acquisition, and high throughput drug discovery technology, my major areas of emphasis were medicninal chemistry and new target and drug discovery against cancer and infectious diseases, particularly tuberculosis.

    Research:

    In 2012, I joined the University of Alabama at Birmingham to pursue a long time dream of supporting advanced education while also focusing on independent research in drug design against cancer and infectious diseases.

    • Research Overview

  • I have broad research interests from pure organic synthesis and the generation of novel, biologically relevant chemical diversity to medicinal chemistry and drug design targeting cancer and underserved diseases such as tuberculosis.

    Currently, my programs primarily involve drug design against single and essential targets in Mycobacterium tuberculosis including the asparyl-t-RNA synthetase (AspS), filamenting temperature sensitive protein Z (FtsZ), D-alanyl-D-alanine ligase (Ddl) and the highly related cell wall ligases MurC-F (crucial enzymes in cell wall biosynthesis), and shikimate kinase (MtSK).

    Many of these proteins are ATP dependent, highlighting my recent focus on analyzing and understanding the complete mycobacterial ATP binding proteome (ATPome) as an ideal and essential set of proteins for new drug development against tuberculosis. These proteins are essential for a variety of crucial cellular processes from environmental sensing and metabolic adaptation (the Pkn serine-threonine protein kinases) to energetic and catalytic pathways (topoisomerases, gyrases and cell wall attendant ligases such as Ddl and MurC-F). Furthermore, this area is timely with the rich datasets and protein structures available relating to the human kinome, allowing comparative inhibitor and crystal structure analyses in order to develop selective agents that target the bacterial proteins only.

    Finally, and relating to my early interests and roots in anticancer drug discovery, I have begun a collaboration with Dr. Zaneta Nikolovska-Coleska, the University of Michigan, investigating the epigenetic target Disruptor-of-Telomeric-Silencing-1-Like (DOT1L) protein. This early stage program has identified novel drug–like non-nucleosides that may represent significant potential for development of new drugs targeting this crucial histone methyltransferase in mixed lineage leukemias (MLL). Optimized small molecules may have advantages over the current, first-in-class clinical agent Pinometostat that demonstrates typical issues of nucleoside-based drugs (poor bioavailability and significant hepatic metabolism and clearance).

    Keywords - Organic and Medicinal Chemistry, Rational Drug Design, Infectious Diseases and Cancer

    • Principal Investigator On

    Education And Training

  • Doctor of Philosophy in Organic Chemistry, Duke University 1985
  • Bachelor of Science or Mathematics in Chemistry, University of Virginia 1978

    • Full Name

  • Robert Reynolds