Helena Safavi-Hemami

Assistant Professor of BiochemistrySafavi

M.Sc. University of Cologne

Ph.D. University of Melbourne

Research

References

helena.safavi@utah.edu

Helena Safavi-Hemami's Lab Page

Helena Safavi-Hemami's PubMed Literature Search

Molecular Biology Program

Biological Chemistry Program

Animal venoms, drug discovery, natural products, venom evolution, therapeutics, diabetes, pain

Research

Venomous animals have evolved large libraries of bioactive compounds that are all targeted at disrupting the physiology and/or behavior of other organisms. The venoms of marine cone snails have been particularly useful because of the high diversity and specificity of peptides that potently target receptors, ion channels and transporters in prey. These molecular targets play critical roles in health and disease rendering cone snail venoms ideal sources for the discovery of pharmacological tools and therapeutics for a wide range of conditions including pain, epilepsy, stroke and autoimmune disease.

Our research centers on applying novel computational and experimental tools for the discovery of toxins with therapeutic potential. We are particularly interested in small peptide toxins that mimic endogenous receptor ligands in prey, including venom peptides involved in glucose homeostasis (e.g., venom insulins) and pain (e.g., neurotensin-like peptides).

Figure 1

Figure 1: Diversity of predatory marine gastropods sequenced for drug discovery

 Figure 2

Figure 2: Cone snails prey on fish, other snails and worms (artwork by Bob Lang)

 Figure 3

Figure 3: Journal cover showing how the geography cone (Conus geographus) captures its fish prey

References

  1. Safavi-Hemami, H.; Brogan, S. E.; Olivera, B. M., Pain therapeutics from cone snail venoms: From Ziconotide to novel non-opioid pathways. J Proteomics2018.10.1016/j.jprot.2018.05.009
  2. Robinson, S. D.; Safavi-Hemami, H., Venom peptides as pharmacological tools and therapeutics for diabetes. Neuropharmacology2017, 127, 79-86.10.1016/j.neuropharm.2017.07.001
  3. Robinson, S. D.; Li, Q.; Lu, A.; Bandyopadhyay, P. K.; Yandell, M.; Olivera, B. M.; Safavi-Hemami, H., The Venom Repertoire of Conus gloriamaris (Chemnitz, 1777), the Glory of the Sea. Mar Drugs2017, 15, (5).10.3390/md15050145
  4. Olivera, B. M.; Raghuraman, S.; Schmidt, E. W.; Safavi-Hemami, H., Linking neuroethology to the chemical biology of natural products: interactions between cone snails and their fish prey, a case study. J Comp Physiol A Neuroethol Sens Neural Behav Physiol2017, 203, (9), 717-735.10.1007/s00359-017-1183-7
  5. Li, Q.; Barghi, N.; Lu, A.; Fedosov, A. E.; Bandyopadhyay, P. K.; Lluisma, A. O.; Concepcion, G. P.; Yandell, M.; Olivera, B. M.; Safavi-Hemami, H., Divergence of the Venom Exogene Repertoire in Two Sister Species of Turriconus. Genome Biol Evol 2017, 9, (9), 2211-2225.10.1093/gbe/evx157
  6. Safavi-Hemami, H.; Lu, A.; Li, Q.; Fedosov, A. E.; Biggs, J.; Showers Corneli, P.; Seger, J.; Yandell, M.; Olivera, B. M., Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa. Mol Biol Evol 2016, 33, (11), 2924-2934.10.1093/molbev/msw174
  7. Safavi-Hemami, H.; Li, Q.; Jackson, R. L.; Song, A. S.; Boomsma, W.; Bandyopadhyay, P. K.; Gruber, C. W.; Purcell, A. W.; Yandell, M.; Olivera, B. M.; Ellgaard, L., Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides. Proc Natl Acad Sci U S A2016, 113, (12), 3227-32.10.1073/pnas.1525790113
  8. Robinson, S. D.; Safavi-Hemami, H., Insulin as a weapon. Toxicon2016, 123, 56-61.10.1016/j.toxicon.2016.10.010
  9. Menting, J. G.; Gajewiak, J.; MacRaild, C. A.; Chou, D. H.; Disotuar, M. M.; Smith, N. A.; Miller, C.; Erchegyi, J.; Rivier, J. E.; Olivera, B. M.; Forbes, B. E.; Smith, B. J.; Norton, R. S.; Safavi-Hemami, H#.; Lawrence, M. C#., A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin. Nat Struct Mol Biol 2016, 23, (10), 916-920.10.1038/nsmb.3292 # equal contribution
  10. Safavi-Hemami, H.; Gajewiak, J.; Karanth, S.; Robinson, S. D.; Ueberheide, B.; Douglass, A. D.; Schlegel, A.; Imperial, J. S.; Watkins, M.; Bandyopadhyay, P. K.; Yandell, M.; Li, Q.; Purcell, A. W.; Norton, R. S.; Ellgaard, L.; Olivera, B. M., Specialized insulin is used for chemical warfare by fish-hunting cone snails. Proc Natl Acad Sci U S A2015, 112, (6), 1743-8.10.1073/pnas.1423857112
  11. Aman, J. W.; Imperial, J. S.; Ueberheide, B.; Zhang, M. M.; Aguilar, M.; Taylor, D.; Watkins, M.; Yoshikami, D.; Showers-Corneli, P.; Safavi-Hemami, H.; Biggs, J.; Teichert, R. W.; Olivera, B. M., Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus. Proc Natl Acad Sci U S A2015, 112, (16), 5087-92.10.1073/pnas.1424435112
  12. Young, N. D.; Nagarajan, N.; Lin, S. J.; Korhonen, P. K.; Jex, A. R.; Hall, R. S.; Safavi-Hemami, H.; Kaewkong, W.; Bertrand, D.; Gao, S.; Seet, Q.; Wongkham, S.; Teh, B. T.; Wongkham, C.; Intapan, P. M.; Maleewong, W.; Yang, X.; Hu, M.; Wang, Z.; Hofmann, A.; Sternberg, P. W.; Tan, P.; Wang, J.; Gasser, R. B., The Opisthorchis viverrini genome provides insights into life in the bile duct. Nat Commun2014, 5, 4378.10.1038/ncomms5378

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Last Updated: 8/6/18