office: Hunter College Belfer Research Building (413 E. 69th Street) BRB 424 (tel 212-896-0449), email email@example.com
Ph.D.: The Rockefeller University, Postdoc: The University of Utah, Paris Museum of Natural History, Max Delbruck Center 2005-2008
Chemical and Biological Diversity: An evolutionary roadmap to discovery and characterization of bioactive peptides from marine organisms
Research projects in the Holford lab applies inventive tools from chemistry and biology to: (1) discover disulfide-rich peptides from a venom source, (2) develop high-throughput methods forcharacterizing structure-function peptide interactions, and (3) deliver novel peptide targets to their site of action for therapeutic application. We use a learn from nature strategy to discover novel peptides from venomous marine snails that could be used to manipulate cellular physiology pertaining to pain and cancer. Our research program is interdisciplinary and collaborative, focused on peptide biology and evolution, with impacts ranging from evolution and molecular systematics to nanotechnology, biomedicine and drug discovery. We have published several papers outlining our venomics peptide drug discovery strategy, which combines venomous snail evolution, phylogeny, and advanced omics technology (Genomics, transcriptomics and proteomics). The correlation between anatomical function and molecular character in venomous marine terebid snails was first identified by in the Holford group and has served as a roadmap for improving the time and cost required to screen new terebrid snail lineages. Recent publications demonstrate the application of nanocontainers for drug delivery and exploring chemical pigmentation in nature. Using viral capsids as nanocontainers, we are pursuing a peptide drug delivery method for delivering snail venom peptides to their molecular site of action. In using viral capsids, we leverage the natural abilities for the nanocontainers to self-assembly, and years of protein conjugation chemistry to modify the exterior and interior of the capsid to serve as a vessel for targeting snail venom peptides to their receptors.
Taxonomy, Phylogeny, and Biochemical Function of Venomous Marine Snails:
Verdes A, Anand P, Gorson J, Jannetti S, Kelly P, Leffler A, Simpson, D, Ramrattan G, Holford M. From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins. Toxins2016, 8, 117.
Moon J, Gorson J, Wright M, Yee L, Khawaja S, Shin Hye, Karma Y, Musunri R, Yun M, Holford M. Characterization and Recombinant Expression of Terebrid Venom Peptide from Terebra Guttata. Toxins , 2016 8.3:63
Fry B, Koludarov I, Jackson T, Holford M, Terrat Y, Casewell N, Unheim E, Vetter I, Ali Sm Low D, Sunagar K. Seeing the Woods for the Trees: Understanding Venom Evolution as a Guide for Biodiversity. Royal Society of Chemistry, 2015 1-36
Kelly P, Anand P, Uvaydov A, Chakravartula S, Sherpa C, Pires E, O'Neil A, Douglas T, Holford M. Developing a Dissociative Nanocontainer for Peptide Drug Delivery. International Journal of Environmental Research and Public Health, 2015 12:10
Anand P, O'Neil A, Lin E, Douglas T, Holford M. Tailored delivery of Analgesic Ziconotide Across a Blood Brain Model Using Nano Containers. Nature Scientific Reports, 2015 5:12497
Gorson J, Ramrattan G, Verdes A, Wright ME, Kantor Y, Srinivasan R, Musunuri R, Packer D, Albano G, Qiu WG, Holford M. Molecular Diversity and Gene Evolution of the Venom Arsenal of Terebridae Predatory Marine Snails. Gen. Biol. Evol, 2015 7(6):1761-1778. doi: 10.1093/gbe/evv10
Modica MV, Puillandre N, Castelin M, Zhang M, Holford M. A Good Compromose: Rapid and Robust Species Proxies for Inventorying Biodiversity Hotspots Using the Terebridae (Gastropoda: Conoidea), PLoS ONE, 2014 9(7): e102160. doi: 10.1371/journal.pone.0102160
Anand P, Grigoryan A, Bhuiyan MH, Ueberheide B, Russell V, Quinonez, J, Moy, P, Chait, B, Poget, S, Holford, M. Sample Limited Characterization of a Novel Disulfide-Rich Venom Peptide Toxin from Terebrid Marine Snail Terebra Variegata. PLoS ONE, 2014 9(4): e94122. doi: 10.1371/journal.pone.0094122
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
Pigmentation in Nature
Verdes A, Cho W, Hossain M, Brennan PLR, Hanley D, Grim T, Hauber ME, Holford M. Nature’s Palette: Characterization of Shared PIgments in Colorful Avian and Mollusk Shells. Plos ONE, 2015. 10:1371.
Lippens D, Branislav Igic, D’Alba L, Hanley D, Verdes I, Holford M, Waterhouse G, Grim T, Hauber M, Shawkey M. The Cuticle Modulates Ultraviolet Reflectance of Avian Eggshells. Biology Open 2015, bio. 012211
Igic B, Nunez V, Voss HU, Croston R, Aidala Z, Lopez AV, Van Tatenhove A, Holford M. Shawkey MD, Hauber ME. Using 3D Pirnted Eggs to Examine the Egg-rejection Behavior of Wild Birds. PeerJ, 2015 3:e965
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 M, 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 M, Muir TW. Adding 'splice' to protein engineering. Structure 1998 AUG;6(8):951-956.
Advancing International Scientific Collaboration:
Holford M & Nichols R, “A Tale of Two States,” Science 2015 349:6247
Holford M, “Made-to-measure postdocs,” Nature 2006; 443:1028
Holford M, “Taking Chemistry Global - International Opportunities for Chemists,”
ACS Graduate Education Newsletter, Fall 2005; 4(2):7.
Slimowitz J & Holford M, “International Activities and the US National Science Foundation”, Bridges, Vol 6. July 2005: http://www.ostina.org/html/bridges/article.htm?article=1251
Education and Outreach:
Holford M, “Informal Science Meets the Lab Bench,” JGH Progress Magazine, Vol 4 (1), Winter 2007: http://justgarciahill.org/jghdocs/webarticledtl.asp?AID=313
Holford M, “Mentors, Museums, and Venomous Snails,” JGH Progress Magazine, Vol 4 (1), Winter 2007: http://justgarciahill.org/jghdocs/websixsec.asp
Honors and Awards
2015 Alfred P. Sloan CUNY Junior Faculty Award
2014 National Academy of Sciences Arab-American Frontiers of Science, Engineering, and Medicine Fellow
2014 Elected New Champion Young Scientist at World Economic Forum Annual Meeting of New Champions
2013 Camille Dreyfus Teacher Scholar Award
2012 Felix Gross Endowment Award
2011 Selected as 21st Century Scientist for NBC-Learn, Chemistry Now series http://www.nbclearn.com/chemistry
2011-2016 NSF CAREER Award
2006-2008 NSF Postdoctoral Fellowship
2004-2005 AAAS Science and Technology Fellowship