Kerr Research Group

  

 

The Marine Natural Products Group at the University of Prince Edward Island is engaged in projects directed at the development of sustainable production methods of bioactive marine metabolites and discovering new bioactive bioproducts. The latter group includes metabolites with activities in assays of relevance to human and animal health, and with activity as antifouling agents.

 

 Contact us

 

  

 

Russell Kerr

 
 

Russell G. Kerr
 
Department of Chemistry, and Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island

 
 
Mailing address:
Russell Kerr
University of Prince Edward Island
Duffy Research Center (NRC-INH)
550 University Avenue
Charlottetown, PEI, C1A 4P3
Canada
 
Contacts:
Email: rkerr@upei.ca
Phone:  (902) 566-0565 
Fax: (902) 566-7445
Office: Duffy Research Center (NRC-INH) Rom 531

 
 
Biographical Information
 
B.Sc. University of Calgary 1982
Ph.D. University of Calgary 1987
Postdoctoral Fellow Stanford Univeristy (with C. Djerassi) 1987 - 1991
Academic Appointments:
1991-1996 Assistant Professor, Department of Chemistry, Florida Atlantic University.
1996-1998 Associate Professor, Department of Chemistry, Florida Atlantic University.
1998-2006 Professor, Department of Chemistry & Biochemistry, Florida Atlantic University.
1999-2006 Professor of Biomedical Sciences, Florida Atlantic University.
2000-2006 Director of Graduate Studies, Department of Chemistry & Biochemistry, Florida Atlantic University.

2003-2006 Director, Center of Excellence in Biomedical and Marine Biotechnology, Florida Atlantic University
2006- Professor & Canada Research Chair, Dept. of Chemistry, UPEI
2006- Professor, Department of Biomedical Sciences, Atlantic Veterinary College, UPEI
Awards:
2006 Canada Research Chair (Tier 1) in Marine Natural Products
2004 Researcher of the Year, Florida Atlantic University
2003 Admitted to “Who's Who in Sciences Higher Education (WWSHE)”
2000 President’s Research Development Award (FAU)
2000 Elected as “Young Observer” for the U.S. National Committee for the International Union of Pure and Applied Chemistry (IUPAC)
1999 Cancer Drug Discovery study section, American Cancer Society (1999-2003)
1998 Charles Schmidt College of Science Distinguished Teacher of the Year
1997 Elected to Sigma Xi
1997 Phi Kappa Phi faculty award (FAU)
1997 Excellence in Undergraduate Teaching Award, Florida Atlantic University
1996 Henry Dreyfus Teacher-Scholar Award
1996 Researcher of the Year Award (Assistant Prof. level), FAU
1995 Teaching Incentive Program Award, FAU
1992 American Society of Pharmacognosy Research Initiation Award
Scientific Affiliations:
Chemical Institute of Canada
American Chemical Society
American Association for the Advancement of Science
American Society of Pharmacognosy
American Association for Cancer Research
Editorial Boards:
Letters in Organic Chemistry
Marine Drugs
The Open Organic Chemistry Journal
Research Letters in Organic Chemistry
 

 

Current Projects

 

  The Marine Natural Products Group at the University of Prince Edward Island is engaged in projects directed at the development of sustainable production methods of bioactive marine metabolites and discovering new bioactive bioproducts. The latter group includes metabolites with activities in assays of relevance to human health and with activity as antifouling agents.
 
  Our discovery program encompasses both macroorganisms (e.g. sponges, tunicates, octocorals, algae) and microbes as sources of bioactive compounds. These organisms are collected from diverse marine habitats in the Caribbean and Atlantic Canada. The library of fractionated extracts generated from these collection programs is screened through a variety of bioassays many of which are collaborative projects with groups at UPEI, NRC-INH, McGill University as well as industrial partners.
  The anti-fouling program aims to identify marine natural products that inhibit the settlement of tunicate larvae and thus offer protection for the mussel and oyster industries. The production methods under development involve a search for bacterial sources of bioactive compounds isolated from marine invertebrates, and the cloning of biosynthetic genes. Students, research associates and post doctoral fellows are involved in many of the facets of marine natural products research including: synthesis, isolation & characterization, microbiology and molecular biology.

Pseudopterosins


The pseudopterosins are a family of diterpene glycosides isolated from the gorgonian Pseudopterogorgia elisabethae. To date, 26 derivatives have been identified (PsA – PsZ) and in most cases, pseudopterosins represent 2-5% of the crude extract. The pseudopterosins are anti-inflammatory and analgesic agents with potencies superior to that of existing drugs such as indomethacin in mouse ear models. They are not active against PLA2, cyclooxygenase and cytokine release or as regulators of adhesion molecules. Evidence suggests the pseudopterosins block eicosanoid release rather than biosynthesis in murine macrophages. Recent data from the Jacobs laboratory (UCSB) indicates that pseudopterosins inhibit inflammation by a novel mechanism suggesting that these metabolites represent a novel class of anti-inflammatory agent. Importantly, one of the pseudopterosins has a substantial commercial market as an additive in personal care products and a simple derivative of pseudopterosin A, methopterosin, has successfully completed a Phase II clinical trial as a topical anti-inflammatory agent.
 
We have a long-standing interest in the biosynthesis of these marine metabolites. We have elucidated the biosynthetic origin of pseudopterosins from geranylgeranyl diphosphate through a series of radiolabeling experiments as well as detailed NMR-directed investigations (Coleman and Kerr 2000, Kohl and Kerr 2003, Ferns and Kerr 2005a, Ferns and Kerr 2005b, Kerr et al. 2006). One of the key steps in the production of the pseudopterosins (and all terpenes) is the cyclization of the appropriate polyprenyl diphosphate. Knowledge of the structure of the cyclase product involved in pseudopterosin biosynthesis provided us with an assay to purify the enzyme responsible for this transformation. This enzyme (elisabethatriene synthase) has been purified to homogeneity (Kohl and Kerr 2004, Brueck and Kerr 2006). A biosynthetic question that is currently under investigation is whether pseudopterosins are produced by the invertebrate host or an associated microbe.

Eleutherobin

 

                                                          

Erythropodium caribaeorum 
Erythropodium caribaeorum (polyps open)
 
Eleutherobin is a diterpene glycoside that has been shown to be a potent cancer cell inhibitor with an IC50 similar to that of paclitaxel (Taxol®). Assays in the National Cancer Institute’s 60 cell line panel showed a 100-fold greater potency over the mean cytotoxicity towards breast, renal, ovarian and lung cancer cell lines. It has also been demonstrated that eleutherobin is active in paclitaxel-resistant cancer cell lines. Significantly, eleutherobin was found to stabilize microtubules by competing for the paclitaxel binding site. The initial discovery of eleutherobin was from an examination of the soft coral Eleutherobia sp. however, development of this drug was severely hampered as no further samples of the coral could be obtained. Eleutherobin and a series of related compounds were subsequently isolated from the Caribbean gorgonian coral Erythropodium caribaeorum.
The sarcodictyins are diterpenes that are closely related to eleutherobin and have been isolated from a number of corals including: Eleutherobia aurea from South Africa, Bellonella albiflora from Japan, Sarcodictyon roseum from the Mediterranean, as well as E. caribaeorum from the Caribbean. The sarcodictyins have been shown to exhibit significant cytotoxicity to various cancer cell lines yet not at the levels of eleutherobin.
A current project in our research group is focused on elucidating the biosynthetic origin of the eleutherobin family of diterpenes. Within our microbiology program, we are also using a variety of culture dependent and culture independent methods to assess the microbial diversity in Erythropodium caribaeorum.

Drug discovery

One major emphasis of our research group is a natural products drug discovery program based on both macroorganisms (invertebrates and algae) and microbes. Collections are from regions in the Caribbean and Atlantic Canada. We generally plan one or two 10 day trips to the Caribbean each year and also collect locally (PEI and surrounding areas) in shorter trips. Extracts are fractionated and screened through collaborations within UPEI, the NRC-Institute of Nutrisciences and Health, as well as other academic partners in Canada and the US.

 

 

 

 

Discovery of anti-fouling agents

 

 The Prince Edward Island mussel industry has become a significant economy since the mid 1980s. Currently the shellfish farmers are facing serious problems from invasive fouling species, especially tunicates that have been a major concern to the PEI farmers as well as farmers around the world. It is clear that once established, it is difficult to control or eradicate invasive tunicates, therefore, preventing tunicate larval settlement appears to be an attractive option. Our general aim is to identify marine natural products that are capable of inhibiting the settlement of tunicate larvae.

 

 

 

 

 

Microbial Diversity Studies

 

We have a variety of ongoing projects aimed at describing the microbial diversity in gorgonians and unusual marine sediments. Culture-dependent and culture-independent techniques are both being employed.

 

 

 

Field Work


2008 Expedition to the Bahamas

Our 2008 Collection Trip to the Bahamas

 

  

In August, we visited the Gerace Research Centre located on San Salvador in the Commonwealth of the Bahamas.  This was a highly successful trip with samples collected from a variety of habitats including reefs, caves and marine lakes.  Samples are now being processed for our drug discovery program and microbiological studies. 

 

 

 

 

 

  
 
An aereal view of the airport on San Salvador - one of our dive sites is directly off shore from the runway.   

 
The Gerace cafeteria. 
Our dive boat for the week.

 
Dovi, Veronica, Fabrice, Doug and Russ

 
 
Stacey collecting
 
Off on the search...

 
 
 
Stacey meets a very friendly grouper known by the locals as Sponge Bob!
A specimen of Pseudopterogorgia elisabethae in the ziploc bag ready for micro work back at the lab.
 
Collecting a gorgonian for microbiological work. 
 
Brad and Fabrice collecting Erythropodium.
Brad - off to the lab.
 
 
Veronica and Brad processing samples for microbiological work.

 
 Fabrice examining a gorgonian. 

 
   
   
   

 

2007 Expedition to the Florida Keys

The trip to Florida was largely directed at collections of invertebrates and algae for a drug discovery program. Rather than staying on a research vessel as we have done in the past, this trip involved small boats with hotel rooms sometimes being used as a lab! Collections were made off Boca Raton, Key Largo, Marathon Key and Summerland Key. At Summerland Key, we stayed at the Mote Tropical Research Lab which is an ideal location for such field work

 

 

 
 
 
 
 

2006 Expedition to the Bahamas

Our trip to the Bahamas in June of 2006 focused on several projects as is characteristic of these expeditions. Several gorgonians were collected for a project aimed at determining the bacterial diversity within these organisms using culture dependent and culture-independent methods. Some of these activities were linked with questions about the source of terpene biosynthesis in such corals.Collections of invertebrates, algae and sediment were made for our drug discovery program. Sites visited on the expedition included: Bimini, Russel Cay, Eleuthera (south end), Sweetings Cay, Cross Harbour and Peterson Cay.

Publications

Lory Z. Santiago-Vázquez, Thomas B. Brück, Wolfram M. Brück, Angela P. Duque-Alarcón, Peter J. McCarth2 and Russell G. Kerr. The diversity of the bacterial communities associated with the azooxanthellate hexacoral Cirrhipahtes lutkeni. Journal of the International Society for Microbial Ecology, in press.

Lory Z. Santiago-Vázquez, Nealie C. Newberger, and Russell G. Kerr. Cryopreservation of the dinoflagellate symbiont of the octocoral Pseudopterogorgia elisabethae. Marine Biology, in press.

Thomas Brueck, Wolfram Brueck, Lory Z. Santiago-Vázquez, Peter McCarthy and Russell G. Kerr. Diversity of the bacterial communities associated with the azooxanthellate deep water octocorals Leptogorgia minimata, Iciligorgia schrammi and Swiftia exertia. Marine Biotechnology, 9, (2007).

Xing Dai, Zhongliang Wan, Russell G. Kerr, and Huw M. L. Davies. Synthetic and isolation studies related to the marine natural products (+)-elisabethadione and (+)-elisabethamine. J. Org. Chem. 72, 1895-2000 (2007).

Lory Z. Santiago-Vázquez, Llanie K. Ranzer, and Russell G. Kerr. Comparison of two total RNA extraction protocols using the marine gorgonian coral Pseudopterogorgia elisabethae and its symbiont Symbiodinium sp. Electronic Journal of Biotechnology, 9(5), (2006).

M. Isabel Nieto, Noemi Gonzalez, Jamie Rodriguez, Russell G. Kerr and Carlos Jimenez. New cytotoxic cembranolides: isolation, biogenetic studies and synthesis of analogues. Tetrahedron 62, 11747-11754 (2006).

Nealie Newberger, Llanie Ranzer, Jennifer Boehnlein and Russell Kerr. Induction of terpene biosynthesis in the dinoflagellate symbionts of the Caribbean gorgonian corals of the genera Pseudopterogorgia and Eunicea. Phytochem. 67, 2133-2139 (2006).

Russell G. Kerr, Amber Kohl and Tyrone Ferns. Elucidation of the biosynthetic origin of the anti-inflammatory pseudopterosins. J. Ind. Microbiol. Biotechnol. 33, 532-538 (2006).

Thomas Brueck and Russell Kerr. Purification and kinetic properties of elisabethatriene synthase from the coral Pseudopterogorgia elisabethae. Comp. Biochem. and Physiol. Part B 143, 269-278 (2006).

Tyrone Ferns and Russell Kerr. Oxidations of erogorgiaene in pseudopterosin biosynthesis. Tetrahedron 61, 12358-12365 (2005).

Jennifer Boehnlein, Lory Santiago-Vazquez and Russell Kerr. Diterpene biosynthesis by the dionflagellate symbiont of the Caribbean gorgognian Pseudopterogorgia bipinnata. Mar. Ecol. Prog. Ser. 303:105-111 (2005).

Tyrone Ferns and Russell Kerr. Identification of amphilectosins as key intermediates in pseudopterosin biosynthesis. J. Org. Chem. 70, 6152-6157 (2005).

Russell G. Kerr, Jennifer Boehnlein, Nealie Newberger and Llanie Ranzer. Concentrations of anti-inflammatory compounds increased in culture studies of coral, microalgae. Global Aquaculture Advocate, 70, (2004).

Jamie Frenz, Amber Kohl and Russell Kerr Kerr; Marine Natural Products as Therapeutic Agents – Part 2. Expert Opinion on Therpeutic Patents; 14, pp 17-33 (2004).

Amber Kohl and Russell Kerr. Identification and characterization of the pseudopterosin diterpene cyclase, elisabethatriene synthase, from the marine gorgonian, Pseudopterogorgia elisabethae. Arch. Biochem. Biophys. 424, 97-104 (2004).

Maysoon B. Saleh and Russell G. Kerr. Oxidation of Tyrosine Diketopiperazine to DOPA Diketopiperazine with Tyrosine Hydroxylase. J. Nat. Prod. 67, 1390-1391 (2004).

Amber Kohl and Russell Kerr. Pseudopterosin biosynthesis: Aromatization of the diterpene cyclase product, elisabethatriene. Marine Drugs, 1, 54-65 (2003).

Laura Mydlarz, Robert Jacobs, Jennifer Boehnlein and Russell Kerr. Evidence that the origin of pseudopterosinn biosynthesis resides in the dinoflagellate symbiont of Pseudopterogorgia elisabethae. Chemistry and Biology, 10, 1051-1056 (2003).

Amber Kohl and Russell Kerr A postulated biosynthetic origin of pseudopterosins and a proposed chemoenzymatic production method. J. Indust. Microbiol. 30, 495-499 (2003).


Athar Ata, Russell Kerr, Claudia Moya and Robert Jacobs. Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae. Tetrahedron. 59, 11389 (2003).

J. Cho, J. Choi, I Kong, S. Park, R. Kerr and Y. Hong. A procedure for axenic isolation of the marine microalgae Isochrysis galbana from heavily contaminated mass cultures. J. Appl. Phycol. 14, 385-390 (2002).

Noemí González, Jaime Rodríguez, Russell G. Kerr and Carlos Jiménez. Cyclobutenbriarein A, the First Diterpene with a Tricyclo[8.4.0.03,6]tetradec-4-ene Ring System from the Gorgonian Briareum asbestinium. J. Org. Chem. 67, 5117-5123, (2002).

Renee S. Thornton and Russell G. Kerr. Induction of Pseudopterosin Biosynthesis in the Gorgonian Pseudopterogorgia elisabethae. J. Chem. Ecol. 28, 2083-2090 (2002).

Jinghai Wen and Russell Kerr. Purification and Characterization of the Fatty Acid Synthase from Bugula neritina. Comp. Biochem. and Physiol. Part B, 128, 445-450 (2001).

Russell Kerr, Amber C. Kohl, Jennifer M. Boehnlein, “Bioactive Compounds from Bryozoans” in “Marine Biotechnolgy” Volume 6, Elsevier, 2001.

Russell Kerr; Biosynthesis of Marine Natural Products, in “Studies in Natural Product Chemistry”, Elsevier Science Publishers, Amsterdam; Vol. 21 pp 293-328 (2000).

Amber Coleman and Russell Kerr. Radioactivity-guided Isolation and Characterization of the Bicyclic Pseudopterosin Diterpene Cyclase Product from Pseudopterogorgia elisabethae. Tetrahedron, 56, 9569-9574 (2000).

Shanti Jeedigunta, Joann Krenisky and Russell Kerr. Diketopiperazines as advanced intermediates in the biosynthesis of ecteinascidins. Tetrahe dron 56, 3303-3307 (2000).

Athar Ata and Russell Kerr. Elisabethamine: a new diterpene alkaloid from Pseudopterogorgia elisabethae. Tetrahedron Letters 41, 5821-5825 (2000).
Samina Naz, Russell Kerr and Ramaswamy Narayanan. New antiproliferative epoxysterols from Pseudopterogorgia americana. Tetrahedron Letters 41, 6035-6040 (2000).

Athar Ata and Russell Kerr. Athar Ata and Russell Kerr. 12-Acetoxypseudopterolide: A New Diterpene from Pseudopterogorgia elisabethae. Heterocycles, 53, 717 (2000).

Amber C. Coleman, Laura Mydlarz and Russell Kerr. In Vivo and In Vitro Investigations into the Biosynthetic Relatedness of the Pseudopterosins. Organic Letters, 1, 2173-2175 (1999).

Paul Andrade, Robin Willoughby, Shirley Pomponi and Russell Kerr. Biosynthetic Studies of the Alkaloid, Stevensine, in a Cell Culture of the Marine Sponge Teichaxinella morchella. Tetrahedron Letters, 40, 4775-4778 (1999).

R.G. Kerr and S.S. Kerr; Marine Natural Products as Therapeutic Agents. Expert Opinion on Therpeutic Patents; 9, 1207-1222 (1999).

Russell Kerr, Richard Vicchiarelli and Stacey Kerr. Identification and biosynthetic origins of sterols in the marine bryozoan Bugula neritina. J. Nat. Prod. 62, 468-470, (1999).

Russell Kerr and Kathleen Kelly. An enzyme-based formaldehyde assay and its utility in a sponge sterol biosynthetic pathway. J. Nat. Prod. 62, 201-202, (1999).

Jens Knauer, Russell G.Kerr, David Lindley and Paul C. Southgate. Sterol Metabolism of Pacific Oyster (Crassostrea gigas) Spat. Comp. Biochem. and Physiol.,119B, 81 - 84 (1998).

Russell Kerr, Cathy Foss, Shigeki Matsunaga and Nobohiro Fusetani. Isolation and structure elucidationof epipolasterol and 22,23 dihydroepipolasterol from the marine sponge Epipolasis sp. Comp. Biochem. and Physiol.,117B, 5651-563 (1997).

Russell Kerr and Lesbeth Rodriguez. A chemoenzymatic production of 9(11)-secosteroids using and enzyme preparation of the gorgonian Pseudopterogorgia americana. In Vitro Cellular and Developmental Biology 33, 20A (1997).

Russell Kerr, Lesbeth Rodriguez and Jaelle Kellman. A chemoenzymatic synthesis of 9(11)-secosteroids using an enzyme extract of the marine gorgonian Pseudopterogorgia americana., Tetrahedron Letters. 37, 8301 (1996).

Russell Kerr, Joseph Lawry and Kim Gush. In vitro biosynthetic studies of the bryostatins, anti-cancer agents from the marine bryozoan Bugula neritina., Tetrahedron Letters. 37, 8305 (1996).

Xueshu Zhang, Ruiwen Zhang, Hui Zhao, Hongying Cai, Kimberly Gush, Russell Kerr, George Pettit and Andrew Kraft. Preclinical Pharmacology of the Natural Product Anticancer Agent Bryostatin 1, an Activator of Protein Kinase C. Cancer Research 56, 802 (1996).

Russell Kerr and Neil Miranda. Biosynthetic studies of ecteinascidins in the marine tunicate Ecteinascidia turbinata. J. Nat. Prod. 58, 1618 (1995).

Russell Kerr, Kathleen Kelly and Aaron Schulman. A novel biosynthetic route to pregnanes in the marine sponge Amphimedon compressa. J. Nat. Prod. 58, 1077 (1995).

Russell Kerr and Zhengjian Chen. In vivo and in vitro biosynthesis of saponins in Sea Cucumbers (Holothuroidea). J. Nat. Prod. 58, 172 (1995).

Russell Kerr and Michelle Kelly-Borges. Biochemical and morphological heterogeneity in the Caribbean sponge Xestospongia muta. Sponges in Time and Space, Proc. Int. Porifera Congress, 4th 65-73 (1994).

Russell Kerr, S.L. Kerr, Jane Formont, Martin Riddle and Peter Murphy. Chemotaxonomic relationships within, and comparisons between, the orders Haplosclerida and Petrosida (Porifera: Demospongiae) using sterol complements. Biochem. Syst. Ecol. 22, 735 - 52 (1994).

R.G. Kerr and P. Southgate; Isolation of gorgosterol from symbiont-free giant clam eggs and larvae. Comp. Biochem. and Physiol 104B, 707 (1993).

B.J. Baker and R.G. Kerr; Biosynthesis of Marine Sterols. in "Topics in Current Chemistry" 167, 1-31 (1993).

R.G. Kerr and B.J. Baker; Marine Sterols - A Review. Nat. Prod. Rep. 8, 465 (1992).

R.G. Kerr, S.L. Kerr, S. Malik and C. Djerassi; Biosynthetic Studies of Marine Lipids 38. Mechanism and Scope of Sterol Side Chain Dealkylation in Sponges; Evidence for Concurrent Alkylation and Dealkylation. J. Am. Chem. Soc. 114, 299 (1992).

R.G. Kerr, S.L. Kerr and C. Djerassi; Biosynthetic Studies of Marine Lipids 26. Elucidation of the Biosynthesis of Mutasterol, a Sponge Sterol with a Quaternary Carbon in its Side Chain. J. Org. Chem. 56, 63 (1991).

R.G. Kerr, S.L. Kerr, G.R. Pettit, D.L. Herald, T.L. Groy and C. Djerassi; Sterols of Marine Invertebrates 63. Isolation and Structure Elucidation of Sutinasterol, the Major Sterol of the Marine Sponge Xestospongia sp. J. Org. Chem. 56, 58 (1991).

R.G. Kerr, B.J. Baker, S.L. Kerr and C. Djerassi; Biosynthetic Studies of Marine Lipids 29. Demonstration of Sterol Side Chain Dealkylation Using Cell-Free Extracts of Marine Sponges. Tetrahedron Lett. 31, 5425 (1990).

R.G. Kerr, I.L. Stoilov, J.E. Thompson and C. Djerassi; Biosynthetic Studies of Marine Lipids 16. De Novo Sterol Biosynthesis in Sponges. Incorporation and Transformation of Cycloartenol and Lanosterol into Unconventional Sterols of Marine and Freshwater Sponges. Tetrahedron 45, 1893 (1989).

S. Malik, R.G. Kerr and C. Djerassi; Biosynthetic Studies of Marine Lipids 19. Dealkylation of the Sterol Side Chain in Sponges. J. Am. Chem. Soc. 110, 6895 (1988).

M.L. Cordeiro, R.G. Kerr and C. Djerassi; Biosynthetic Studies of Marine Lipids 15. Conversion of Parkeol (Lanost-9(11),24-dien-3b-ol) to 14a-methylcholest-9(11)-en-3b-ol in the Sea Cucumber Holothuria arenicola. Tetrahedron Lett. 2159 (1988).

Sponsorship

Research is currently sponsored by the following agencies.

 

 

 

Canada Foundation for Innovation

 

 

Canada Research Chairs

 

 

 

The Jeanne and J.-Louis Lévesque Foundation

 

 

University of Prince Edward Island

 

 

Tech PEI


 

The Atlantic Innovation Fund




 

 

 

 

 

NSERC