Ph.D., The Rockefeller University Ph.D. The Rockefeller University, Postdoc: The University of Utah, Paris Museum of Natural History, Max Delbruck Center 2005-2008

Chemical Biology and Physical and Organic Chemistry

Chemical and Biological Diversity: An evolutionary roadmap to discovery and characterization of bioactive peptides from marine organisms The peptidic toxins found in the venom of Toxoglossate (“poisoned-tongued”) marine snails (cone snails, terebrids, and turrids), have been identified as effective biochemical tools for studying the structure-activity relationships of ion channels in the nervous system. The first marine snail drug, ziconotide (Prialt), used to alleviate chronic pain in HIV and cancer patients, is a major breakthrough that caused a paradigm shift in analgesic drug development. The pharmacological and biological diversity of toxoglossate peptide toxins present a vibrant and largely unexplored repository for investigating ion channels and receptors. To date the majority of snail toxins characterized are from cone snails, conotoxins, however, more recent efforts have identified the peptide toxins of terebrids and turrids as equally viable for investigating the mechanics of the neuronal circuit. Dr Holford’s research applies inventive tools from chemistry and biology to: (1) identify disulfide rich peptide toxins from a venom source, (2) develop high-throughput methods for characterizing structure-function peptide interactions, and (3) produce novel peptide targets for therapeutic development.

Castelin, M, Puillandre, N, Kantor, Yu.I, Terryn, Y, Cruaud, C, Bouchet, P, Holford, M. Macroevolution of venom apparatus innovations in auger snails (Gastropoda; Conoidea; Terebridae), Molecular Phylogenetics and Evolution, 2012 Jul;64(1):21-44 DOI: http://dx.doi.org/10.1016/j.ympev.2012.03.001.

Puillandre, N. Modica, MV, Zhang, Y, Sirovich, L, Boisselier, M -C, Cruaud, C, Holford, M, Samadi, S. Large-scale species delimitation method for hyperdiverse groups, Molecular Ecology, 2012, Jun;21(11):2671-2691. doi: 10.1111/j.1365-294X.2012.05559.x

Puillandre, N, and Holford, M. The Terebridae and Teretoxins: Combining phylogeny and anatomy for the concerted discovery of bioactive compounds. Chemical Biology, 2010, 10:7.

Modica, MV, and Holford, M. The Neogastropoda: Evolutionary Innovations of Predatory Marine Snails with Remarkable Pharmacological Potential, in P. Pontarotti (ed.), Evolutionary Biology – Concepts, Molecular and Morphological Evolution, DOI 10.1007/978-3-642-12340-5_15, # Springer-Verlag Berlin Heidelberg 2010.

Holford, M., Puillandre, N, Modica, MV, Watkins, M, Collin, R, Bermingham, E, Olivera, BM. Correlating molecular phylogeny with venom apparatus occurrence in Panamic Auger Snails (Terebridae). PLoS One. 2009, 4(11): e7667.

Holford, M, Auer, S., Laqua, M., Ibañez-Tallon, I. Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators. Frontiers in Neuroscience. 2009 2:1-10. doi: 10.3389/neuro.02.021.2009

Holford, M, Puillandre, N, Terryn, Y, Cruaud, C, Olivera, BM, Bouchet, P. Evolution of the Toxoglossa Venom Apparatus as Inferred by Molecular Phylogeny of the Terebridae. Molecular Biology and Evolution, 2009 26(1):15-25. doi:10.1093/molbev/msn211

Holford, M, Zhang, M, Catlin, P, Azam, L, K. Hanumae, G., Green, BR, Watkins, M, Ownby, JP, Yoshikami, D, Bulaj, G, Olivera, BM. Pruning Nature: Biodiversity-Derived Discovery of Novel Sodium Channel-Blocking Conotoxin from Conus bullatus. Toxicon 2009 53: 90-98. http://dx.doi.org/10.1016/j.toxicon.2008.10.017

Khöler, F, Holford, M, Van Tuo, D, Thanh Hai, H. Exploring a largely unknown fauna: On the diversity of pachychilid freshwater gastropods in Vietnam (Caenogastropoda: Cerithioidea). Molluscan Research, 2009. 29(3): 121–146.

Terryn, Y, and Holford, M. The Terebridae of the Vanuatu Archipelago with a Revision of the Genus Granuliterebra Oyama 1961, the Description of a New Genus and a Three New Species. Visaya 2008 December Supplement 3. ISSN 1656-4.650. ISBN 978-3-929767-20-6

Development and Application of Expressed Protein Ligation (peer-reviewed):

Minakhin L, Camarero JA, Holford M, Parker C, Muir TW, Severinov K., Mapping the molecular interface between the sigma (70) subunit of E. coli RNA polymerase and T4 AsiA. J Mol Biol 2001 MAR 2;306(4):631-642.

Huse M, Holford MN, Kuriyan J, Muir TW, Semisynthesis of hyperphosphorylated type I TGF Beta receptor: Addressing the mechanism of kinase activation. J Am. Chem. Soc. 2000 AUG 30;122(34):8337-8338.

Ayers B, Blaschke UK, Camarero JA, Cotton GJ, Holford M, Muir TW. Introduction of unnatural amino acids into proteins using expressed protein ligation. Biopolymers 1999;51(5):343-354

Holford MN, Muir TW, Adding 'splice' to protein engineering. Structure 1998 AUG;6(8):951-956.