Nathan Ross, PhD
(Co-Mentor: Steve Canham, PhD)
Chemical Biology & Therapeutics
Cambridge, Massachusetts, United States
Our general research interest is in building chemical and genetic tools to enable a biological pathway-based approach to gain mechanistic understanding of disease. While genetics has provided us the parts list for biology, additional approaches are needed to understand how these parts work together in healthy or diseased states. Chemical genetics allows us to fill in some of these knowledge gaps and help identify novel entry points for therapeutic intervention.
A current area of research focus is in the development of chemical and genetic tools in order to elucidate biological pathways of lysosomal storage disorders. Lysosomal storage diseases are a group of ~50 inherited metabolic disorders that result in from defects in lysosomal function. Most disorders are the consequence of a deficiency of a single enzyme required for the catabolism of lipids, glycoproteins, or mucopolysaccharides. Although most of the responsible genes and proteins associated with the different lysosomal storage disorders are known, the link from gene to the observed associated clinical pharmacology is limited. Projects of current interest in our group span a range of pathways relating to lysosomal storage diseases.
Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A complex.
Carelli JD, Sethofer SG, Smith GA, Miller HR, Simard JL, Merrick WC, Jain RK, Ross NT, Taunton J.
Elife, 2015, 4, e10222.
Nannocystin A: an elongation factor 1 inhibitor from Myxobacteria with differential anti-cancer properties.
Krastel P, Roggo S, Schirle M, Ross N, Perruccio F, Aspesi P, Aust T, Buntin K, Estoppey D, Liechty B, Mapa F, Memmert K, Miller H, Pan X, Riedl R, Thibaut C, Thomas J, Wagner T, Weber E, Xie X, Schmitt EK, Hoepfner D.
Angew Chem Int. Ed. 2015, 54, 10149.
Englarin A agonizes the TRPC4/C5 cation channels to inhibit tumor cell line proliferation.
Carson C, Raman P, Tullai J, Xu L, Henault M, Thomas E, Yeola S, Lao J, McPate M, Verkuyl JM, Marsh G, Sarber J, Amaral A, Bailey S, Lubicka D, Pham H, Miranda N, Ding J, Tang HM, Ju H, Tranter P, Ji N, Krastel P, Jain RK, Schumacher AM, Loureiro JJ, George E, Berellini G, Ross NT, Bushell SM, Erdemli G, Solomon JM.
PLOS One 2015, 10, e0127498.
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