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Dr. Frank Mari
Professor
PhD: University of Massachusetts at Amherst
BS: Universidad Simon Bolivar, Caracas, Venezuela

Contact information
Office: S&E 134
Phone: (561) 297-3315
Fax:      (561) 297-2759
Email:   mari@fau.edu
Webpage: Dr. Mari's lab

Research
  • Isolation and Characterization of Peptides and Proteins of Marine Origin
  • Structure and dynamics of peptides and proteins of marine origin using NMR methods
  • Computational methods for the analysis of structure-activity relationships of biomolecules

The current focus of our research program is to study the venom of cone snail species from the Atlantic ocean and the Eastern Pacific region. Cone snails are venomous predatory marine gastropods that use an elaborate biochemical strategy to compete for survival in the marine environment.

The venom of cone snails is a complex mixture of neuroactive peptides (Conopeptides) that elicit a wide range of neurophysiological responses. Several conopeptides show promising properties as neuropharmacological agents for the treatment of a wide array of conditions ranging from chronic pain to the treatment of epilepsy.

The venom of cone snails is species specific. There are more than 1000 cone snail species. Therefore, up to 100,000 biological active conopeptides may exist. Less than 200 conopeptides have fully characterized to date. Our lab is dedicated to collect Atlantic and Panamic cone snails species, separated and isolate the conopeptide components of their venom and to the molecular characterization of these conopeptides. For more details check our research group web site: USS CONOTOXIN.

Recent Publications and Presentations

Janelle Lauer-Fields, Mare Cudic, Shuo Wei, Frank Mari, Gregg B. Fields, and Keith Brew*. “ Engineered Sarafotoxins as Tissue Inhibitor of Metalloproteinases-like Matrix Metalloproteinase Inhibitors”, Journal of Biological Chemistry, 2007, 282(37), 26948-26955.

Mare Cudic, Frank Mari, and Gregg B. Fields*. “Synthesis and Solid-Phase Application of Suitably Protected g -Hydroxyvaline Building Blocks”. Journal of Organic Chemistry, 2007, 72(15), 5581-5586.

Carolina Möller and Frank Mari*. “A Vasopressin/Oxytocin Related Conopeptide with a Gla at Position 8” Biochemical Journal, 2007, 404, 413-419.

Carolina Möller, Sanaz Rahmankhah, Janelle Lauer-Fields, Jose Bubis, Gregg B. Fields, and Frank Mari*. “A Novel Conotoxin Framework with a Helix-Loop-Helix (Cs a/a ) Fold”. Biochemistry, 2005, 44, 15986-15996.

Katarzyna Pisarewicz, David Mora, Fred Pflueger, Gregg Fields and Frank Mari*. "Polypeptide Chains Containing D- g -Hydroxyvaline” J. Amer. Chem. Soc ., 2005, 127, 6207-6215.

Frank Mari* and Gregg B. Fields. “Conopeptides: Unique Pharmacological Agents that Challenge Current Peptide Methodologies”, Chimica Oggi, 2003, 21, 43-48.

Aldo Franco and Frank Mari*. " Three-Dimensional Structure of the a -Conotoxin EI Determined by 1H NMR Spectroscopy ", Lett. Peptide Sci., 1999, 6, 239-51.

Manuel Marquez, Frank Mari* and Carlos Gonzalez*. "Ab Initio Study of the Reaction Between a Series of Substituted Single Nitrenium Ion with Water", J. Phys. Chem. A, 1998, 103, 6191-6199.

Albeiro A. Restrepo-Cossio, Carlos A. Gonzalez and Frank Mari*. "Comparative Ab initio Treatment (Hartree-Fock, Density Function Theory, MP2 and Quadratic Configuration Interactions) of the Cycloaddition of Phosphorus Ylides with Formaldehyde in the Gas Phase", J. Phys. Chem. A, 1998, 102, 6993-7000.

Cliff Ross, Steve Hevener, Roger Clark, James X. Hartmann and Frank Mari*. "Isolation of Parvalbumin Isotypes by Preparative HPLC Techniques", Prep. Biochem. & Biotech., 1998, 28, 49-60.

Albeiro A. Restrepo-Cossio, Herminsul Cano, Carlos A. Gonzalez and Frank Mari*. "Molecular Modeling of the Wittig Olefination Reaction: MNDO-PM3 and Ab Initio Treatment of the Wittig Reaction of Unstabilized, Semistabilized and Stabilized Ylides with Acetaldehyde", Heteroatom Chem., 1997, 8, 557-569.

Cliff I. Ross, Robert W. Tilghman, James X. Hartmann and Frank Mari*. "Distribution of Parvalbumin Isotypes in Adult Snook (Centropomus undecimalis) and Their Potential Applications as a Species-Specific Biomarker", J. Fish Biol., 1997, 51, 561-572.

John K. Young, Frank Mari, Minzhen Xu, Robert E. Humphreys, Nikki M. Clemente, Donald J. Nelson, Joseph J. Gambino and George E. Wright*. "Structural Studies by 1H of a Prototypic a -Helical Peptides (LYQELQKLTQTLK) and Homologs in Trifluoroethanol/water and on Sodium Dodecyl Sulfate Micelles", J. of Peptide Res., 50, 1997, 122-131.

Robert W. Tilghman, Cliff I. Ross, Frank Mari* and James X. Hartmann. "Parvalbumins as a Biomarker for Fish Species Identification: Applications to Snook (Centropomus undecimalis) Preservation", TRANSACTION/JOURNAL: OCEAN 96, 1996, 1, 1372-1375.

Alex A. Vinogradov, Frank Mari*, Robert E. Humphreys and George E. Wright. " 1H NMR Studies of Prototypical Helical Designer Peptides: a Comparative study of the Amide Chemical Shift Dependency on Temperature and Sequence", Int. J. Peptide Protein Res. 1996, 47,467-476.

Albeiro A. Restrepo, Frank Mari*, Carlos A. Gonzalez* and Manuel Marquez. "Optimizadores Moleculares", Quimica: Actualidad y Futuro, 1995, 2, 101-112.

Chuanyou Zhang, Xiaojun Xie, Frank Mari, Xiaoguang Wang and Donald J. Nelson*. "Interaction of Silver Hake Parvalbumin with Metal Ions and Model Membranes". J.Bioinorg. Chem., 1993, 52, 209-225.

William E. McEwen*, Frank Mari, Paul M. Lahti, Linda L. Baughman and William J. Ward. “Mechanisms of the Wittig Reaction", in "Phosphorus Chemistry", E. N. Walsh, E. J. Griffith, R. W. Parry and L. D. Quin (Eds.), ACS Symp. Ser. No. 486, Chapter 12, pg. 149-161, 1992.

Frank Mari , Paul M. Lahti and William E. McEwen*. “A Theoretical Study of the Wittig Olefination Reaction: MNDO-PM3 Treatment of the Wittig Half-Reaction of Unstabilized Ylides with Aldehydes", J. Amer. Chem. Soc., 114, 813-821 (1992).

Mal-Shick Kim-Shin, Frank Mari, Pramila A. Rao, Thomas R. Stengle, and Pavinee Chinachoti*. " 17O NMR Studies of Water Mobility During Bread Staling", J. Agric. Food Chem., 1991, 39, 1915-1920.

Pavinee Chinachoti*, Mal-Shick Kim-Shin, Frank Mari and Leah Lo. "Gelatinization of Wheat Starch in the Presence of Sucrose and NaCl: The Correlation Between Gelatinization Temperature and the Water Mobility as Determined by 17O NMR." Cereal Chem., 1991, 68, 245-248

Frank Mari , Paul M. Lahti and William E. McEwen*. "Molecular Modeling of the Wittig Olefination Reaction: Part 2: A Molecular Modeling Approach at the MNDO-PM3 Level", Heteroatom Chem., 1991, 2, 265-276.

Frank Mari , Paul M. Lahti and William E. McEwen*. "Molecular Modeling of Oxaphosphetane intermediates of Wittig Olefination Reactions", Heteroatom Chem., 1990, 1, 255-259.

W.E. McEwen*, J. H. Tien, L. M. Rembetsy, B. J. Kalbacher, J. Lubinkowski, F. Mari, S. DeVicenzo, R. M. Salgueiro, J. Hou and J. A. Alvarez. "Displacement and Electron- transfer Reactions of Substituted 2-Chloro-1,3 ,2-Benzodioxastiboles with Bases", Phosphorus and Sulfur, 1988, 36, 153-164.

BOOK CHAPTERS

Frank Mari*, Xiaojun Xie, Jeffrey H. Simpson and Donald J. Nelson*. "Multidimensional NMR Investigation of the Neurotoxic Peptide Mastoparan in the Absence and Presence of Calmodulin", in "Biological NMR Spectroscopy" Chapter 13, pp: 169-182, John L. Markley and Stanley J. Opella (Eds.), Oxford University Press, 1997.

David Mora, Fred C. Pflueger, Katarzyna Pisarewicz, Gregg B. Fields, and Frank Mari*. “A Novel Post-Translational Modification: A Conopeptide from Conus gladiator Provides the First Example of g -Hydroxyvaline (Hyv) within a Polypeptide Chain” in Peptide Revolution: Genomics, Proteomics & Therapeutics, pp. 95-97, M. Chorev and T. K. Sawyer (Eds.), American Peptide Society, San Diego, CA (2004).

Elena Matei, Fred Pflueger, Aldo Franco, Herminsul Cano, David Mora, and Frank Mari*. “Structural analysis of nanomolar quantities of marine neuropeptides using 2D-NMR methods”, in Peptide Revolution: Genomics, Proteomics & Therapeutics, pp. 418-419, M. Chorev and T. K. Sawyer (Eds.), American Peptide Society, San Diego, CA (2004).

Aldo Franco, Carolina Moller, Katarzyna Pisarewicz,David Mora, Gregg B. Fields, and Frank Mari*. “Hyperhydroxylation: A New Strategy for Neuronal Targeting by Venomous Marine Molluscs” in Progress in Molecular and Subcellular Biology. Subseries Marine Molecular Biotechnology: Molluscs” Chapter 4, pp: 83-103, G. Cimino and M. Gavagnin (Eds.), Springer-Verlag, Berlin Heidelbeerg, Germany (2006).

PATENT APPLICATIONS:

Frank Mari , “Potassium Channel-Blocking Framework 14 Conopeptides of Conus floridanus floridensis and C. villepinii and their Use in Treatment of Cancer and Pain”. PCT Int. Appl. (2006), 50pp. CODEN: PIXXD2 WO 2006135739 A2 20061221 CAN 146:56867 AN 2006:1337824 CAPLUS.

Frank Mari , “Conopeptides and Methods of Use”. U.S. Pat. Appl. Publ. (2006), 55 pp., Cont.-in-part of U.S. Ser. No. 794,640. CODEN: USXXCO US 2006019892 A1 20060126 CAN 144:156613 AN 2006:79349 CAPLUS.

Frank Mari and Gregg B. Fields, “Conus-Derived g -Hydroxyconophan Peptides, and Methods of Use for Modulation of Ion Levels in Cells”. U.S. Pat. Appl. Publ. (2004), 32 pp. CODEN: USXXCO US 2004176303 A1 20040909 CAN 141:254608 AN 2004:739953 CAPLUS.

COMPETITIVE GRANTS

Grants Awarded:

“Carboxylated Neuroprotective Agents from Cone Snails”, Florida Sea Grant, Amount: $225,000, Funded 8/2007. PI: Frank Mari, Co-PI: Jang Y. Wu, Senior Personnel: Gregg B. Fields.

“ Neuromodulatory Properties of the F14 and F17 Conotoxin Frameworks”, NIH, Amount: $200,000. Awarded 5/2007 (funding disallowed due to another R15 NIH grant award). PI: Frank Mari, Co-PI: Gregg B. Fields.

“Isolation of Novel Conopeptides from the Bahamian Cone Snails VI (The Abacos)”, Florida Institute of Oceanography. Amount: $35,000 (equivalent to 10 days of shiptime – R/V Suncoaster). Funded: 6/2007-5/2008. PI: Frank Mari, Co-PI: Anton Oelinik.

“Neuropharmacology of Conophans and Hydroxyconophans”, NIH, Amount: $200,000. Funded 3/2007. PI: Frank Mari, Co-PI: Gregg B. Fields, Senior Personnel: Charles Luetje and Jang Y. Wu.

“Isolation of Novel Conopeptides from the Bahamian Cone Snails V (The Grand Bahama)”, Florida Institute of Oceanography. Amount: $35,000 (equivalent to 10 days of shiptime – R/V Suncoaster). Funded: 6/2005-5/2006. PI: Frank Mari, Co-PI: Anton Oelinik.

“Medicines from the Sea: Collection of Deep-water Marine Mollusks using Deep Submersible Vehicles”, Center of Excellence for Biomedical and Marine Biotechnology/State of Florida, Amount: $62,500, (equivalent to 5 dives on the Johnson Sea-Link – onboard of the R/V Seward Johnson). Funded 9/2005 (expedition date). PI: Frank Mari.

“Isolation of Novel Conopeptides from the Bahamian Cone Snails IV (Bimini and Cay Sal Bank”, Florida Institute of Oceanography. Amount: $15,400 (equivalent to 7 days of shiptime – R/V Bellows). Funded: 6/2004-5/2005. PI: Frank Mari, Co-PI: Anton Oelinik.

“Isolation, Characterization and Synthesis of Hydroxyconophans: a New Class of Neuropharmacological Agents from Marine Venomous Mollusks”, Division of Sponsored Research, FAU, Amount: $15,000. Funded 10/2003. PI: Frank Mari.

“Isolation, Characterization and Synthesis of Hydroxyconophans: a New Class of Neuropharmacological Agents from Cone Snails”, Florida Sea Grant, Amount: $225,000, Funded 8/2003. PI: Frank Mari. Co-PI: Gregg B. Fields.

“Medicines from the Sea: Collection of Deep-water Marine Mollusks using Deep Submersible Vehicles”, Center of Excellence for Biomedical and Marine Biotechnology/State of Florida, Amount: $25,000, (equivalent to 2 dives on the Johnson Sea-Link – onboard of the R/V Seward Johnson). Funded 5/2004 (expedition date). PI: Frank Mari.

“Medicines from the Sea: Novel Neuropharmacological Agents from Venomous Marine Mollusks”, Center of Excellence for Biomedical and Marine Biotechnology/State of Florida, Amount: $95,000, Funded 7/2003. PI: Frank Mari.

“State of Florida Center of Excellence in Biomedical and Marine Biotechnology”, Amount: $10,000,000, Funded 9/2003. Group Proposal: Principal Offeror: Larry Lemanski, Project Director: Russell Kerr, Co-PI: Frank Mari and others.

“Isolation of Novel Conopeptides from the Floridian Cone Snails of the Dry Tortugas”, Florida Institute of Oceanography. Amount: $15,400 (equivalent to 7 days of shiptime – R/V Bellows). Funded: 6/2003-5/2004. PI: Frank Mari, Co-PI: Anton Oelinik.

“Novel Pharmacological Agents from Conus regius”, NIH, Amount: $150,000, Funded 6/2003. PI: Frank Mari. Co-PI: Gregg B. Fields.

“Isolation of Novel Conopeptides from the Central Bahamian Cone Snails III”, Florida Institute of Oceanography. Amount: $21,000 (equivalent to 7 days of shiptime – R/V Suncoaster). Funded: 6/2002-5/2003. PI: Frank Mari, Co-PI: Anton Oelinik.

“Isolation and Characterization of Novel Pharmacological Agents from Atlantic and Panamic Cone Snails Species, Florida Sea Grant, Amount: $226,000, Funded 2/2001. PI: Frank Mari.

“Purchase of an NMR for Teaching Creative Problem Solving Skills in the Chemistry Laboratory Program at FAU ", NSF ( 0311369) , Amount: $253,333. Group Proposal. Funded 7/2003. PI: Salvatore Lepore, Co-PIs: Frank Mari and Craig Byrdwell.

“Isolation of Novel Conopeptides from the Central Bahamian Cone Snails II”, Florida Institute of Oceanography. Amount: $30,000 (equivalent to 10 days of shiptime – R/V Suncoaster). Funded: 6/2001-5/2002. PI: Frank Mari , Co-PI: Anton Oelinik.

“Isolation of Novel Conopeptides from the Central Bahamian Cone Snails”, Florida Institute of Oceanography. Amount: $15,000 (equivalent to 6 days of shiptime – R/V Bellows). Funded: 6/2000-5/2001. PI: Frank Mari.

“Identification of Novel Conopeptides", Cognetix, Inc, Salt Lake City, UT, Amount: $50,000. Funded 1/2000. PI: Frank Mari.

“Isolation and Characterization of Neuropeptides From the Venom of Floridian Cone Snails (Conus sp.), Division of Sponsored Research, FAU, Amount: $4,650. PI: Frank Mari.

“Isolation of Novel Conopeptides from the Western Bahamian Cone Snails”, Florida Institute of Oceanography. Amount: $10,000 (equivalent to 4 days of shiptime – R/V Bellows). Funded: 6/1999-5/2000. PI: Frank Mari.

“Purchase of a 500MHz Nuclear Magnetic Resonance Spectrometer", Submitted to the Kresge Foundation, Science Initiative Program, Amount: $170,833 (approved towards the purchase of the spectrometer). An additional $170,883 was conditioned upon raising $670,000 in philanthropic gifts. Group proposal submitted by members of the Department of Chemistry and Biochemistry and the Dean's Office of the Charles E. Schmidt College of Science (Senior Scientific Personnel: Gregg B. Fields and Frank Mari, No PI and Co-PI's were specified). Funded 9/98.

"Incorporation of HPLC into a Comparative Methods Approach for Undergraduate Biochemical Laboratory Education", Camile and Henry Dreyfus Foundation, Amount: $26,552.00 (including 50% FAU matching). Group Proposal submitted by Deborah Louda (PI), Jerome Haky (Co-PI) and Frank Mari (Co-PI). Funded 3/98. End Date: 9/99.

"Production and Testing of Immunoassay Kits for the Identification of Billfish Species". National Marine Fisheries Services. PI: James X. Hartmann, Co-PI: Frank Mari. Amount: $19,530. Funded 5/97. End Date: 12/99

"Acquisition of a High-Performance Graphics Supercomputer for the College of Science, FAU", National Science Foundation, Group Proposal, PI: Robin Jordan. Amount: $249,099 (+$250,000 matching from FAU); total for the project $500,000. Funded 2/96. End Date: 1/99.

"Structural Studies of Designer Helical Peptides", National Science Foundation, PI: Frank Mari. Amount: $18,000. Funded 7/96. End Date: 12/98.

"Structural Studies of Designer Helical Peptides", Florida Atlantic University, Research Initiation Award Program, PI: Frank Mari. Amount: $4,900. Funded 1/96. End Date 2/97.

"Structural Studies of Calmodulin-Bound Neuropeptides", Division of Sponsor Research, Florida Atlantic University, Research Initiative Program,. PI: Frank Mari. Amount: $4,989.74. Funded 1/95. End Date: 2/96.

"Structure in Solution of Human Insulin-Like Growth Factor I", FAU Division of Sponsored Research, PI: Frank Mari. Amount: $1,000. Funded 1/94. End Date 1/95.

"Structure in Solution of Human Insulin-Like Growth Factor I when Bound to its Serum Binding Protein IGFBP-3", Diabetes-Endocrinology Research Center, UMMC, PI: Frank Mari. Amount: $20,000. Funded 5/92. End date: 7/93

MEETING SESSIONS CHAIRED

212th American Chemical Society National Meeting, August 1996, Orlando, Fl, Division of Organic Chemistry. Presided the session: NMR Techniques, Reactions and Reaction Mechanisms.

INVITED SEMINARS OR TALKS

Department of Chemistry, Florida International University, "Structural and Dynamical Studies of Peptides and Proteins", Fall 1994.

Department of Biological Sciences, Florida Atlantic University, "Applications of NMR Spectroscopy to Structural Biology", Spring 1994.

Department of Physics, Florida Atlantic University, "NMR Studies of Biomolecules'' Fall, 1995.

Department of Chemistry, University of Miami, "Structural Studies of Biomolecules Using Multidimensional and Multinuclear NMR Spectroscopy", Fall 1996.

Department of Chemistry, Florida Institute of Technology, "Structural and Dynamical Studies of Biomolecules Using NMR Spectroscopy", Fall 1996.

Department of Chemistry, University of South Florida, "Structural and Dynamical Studies of Peptides and Proteins Using NMR Spectroscopy", Spring 1998.

Cognetix Inc., Salt Lake City Utah, “Cone Snails of the Americas as a Novel Source of Conopeptides”, January 2000.

Center for Molecular Biology and Biotechnology, Florida Atlantic University, “Drugs from Marine Snails”, Spring 2000.

Center for Molecular Biology and Biotechnology, Florida Atlantic University, “NMR in the 21st Century: Structural analysis of nanomole quantities of conopeptides using 2D-NMR methods”, Spring 2002.

Xenome Ltd., Brisbane, Australia, “Conopeptides from the Americas”, Fall 2003.

Department of Pharmacology, University of Miami Medical School, "Drugs from the Sea: The New Wave in Marine Neuropharmacology ", Fall 2004.

Department of Chemistry and Biochemistry, Florida International University, "Drugs from the Sea: The New Wave in Marine Neuropharmacology ", Spring 2005.

The Broward County Shell Club, “Cone snails: A Rich Source of Drugs from the Sea”, Spring 2005.

Neuroscience Program, Florida Atlantic University, “Neuroactive Peptides from Marine Sources”, Spring 2007.

Past Grant Reviewing Activities

Proposal Review Board Memberships

National Science Foundation, Member of Review Panel for the Academic Research Infrastructure (ARI) Program, Division of Chemistry, March 1995, Washington DC.

Grants Proposals Refereed ad hoc

National Science Foundation , Chemical Instrumentation and Facilities Program, Reviews Grants Proposals for the Acquisition of NMR equipment.

National Science Foundation , Major Research Instrumentation (MRI) Program, Reviews Grants Proposals for the Acquisition of NMR equipment.

National Science Foundation , Faculty Early Career Development (CAREER) Program, Reviews Grants Proposals in Organic Dynamics and Synthesis and Materials Chemistry.

American Chemical Society , The Petroleum Research Fund (PRF Grants), Reviews Grants Proposals in Organic, Bio-organic, Materials and Computational Chemistry.

SERVICE AND COMMITTEES

Curriculum Committee. College of Science, Florida Atlantic University. Academic Year 1993-1994.

Curriculum Committee, Chair. Department of Chemistry, Florida Atlantic University. Academic Year 1993-1994.

High School Chemathon Committee. Department of Chemistry, Florida Atlantic University. Spring 1994.

Curriculum Committee. College of Science, Florida Atlantic University. Academic Year 1994-1995.

Curriculum Committee, Chair. Department of Chemistry, Florida Atlantic University. Academic Year 1994-1995.

Freshmen-Transfer Open House, Participant Faculty. College of Science, Florida Atlantic University. Spring 1995.

Career Day, College of Science Representative. Florida Atlantic University. Spring 1995.

Chair of the Undergraduate Committee and Undergraduate Advisor. Department of Chemistry, Florida Atlantic University. Academic Year 1995-1996.

Planning Committee. Department of Chemistry, Florida Atlantic University. Academic Year 1995-1996.

Biochemistry Degree Coordinator. Department of Chemistry, Florida Atlantic University. Academic Year 1995-Present.

Curriculum Committee. College of Science, Florida Atlantic University. Academic Year 1995-1996.

Chair of the Planning Committee. Department of Chemistry, Florida Atlantic University. Academic Year 1996-1997.

College Research Facilities Task Force. Charles E. Schmidt College of Science, Florida Atlantic University. Academic Year 1998-1999.

Web Site Coordinator. Department of Chemistry & Biochemistry. Academic Year 1999-Present.

Director of Operations of the NMR and Proteomics Laboratory. Academic Year 1990-Present.

Coordinator of the Seminar Program. Department of Chemistry & Biochemistry. Academic Year 2001-Present.

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