Frederick S. Buckner

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University of Washington
School of Medicine
Medicine
Infectious Diseases
Associate ProfessorAppointed: 2005
Professional Headshot of Frederick S. Buckner

Mailing Address

University of Washington
Infectious Diseases
Box 357185
Seattle, Washington 98195-7185
United States

Contact Information

Phone: (206) 598-9148
Fax: (206) 598-8819
fbuckner@u.washington.edu

Qualifications

M.D., University of Washington, Infectious Diseases, 1988.

Expertise and Research Interests

My primary research interest is drug development for parasitic diseases. I focus on pathogenic protozoa, particularly trypanosomes and leishmania. These organisms cause Chagas disease (Trypanosoma cruzi), Afican sleeping sickness (Trypanosoma brucei), and leishmaniasis. I work to identify cellular processes that may serve as targets for antiparasitic drugs. Some examples of drug targets that I study are sterol biosynthesis, protein prenylation, and glycolysis. I use molecular and biochemical methodsto investigate these cellular processes. I have developed efficient screening methods to test candidate drugs against culture forms of these parasites.

Other Expertise

I am a board certified clinical specialist in Infectious Diseases.

Industrial Relevance

Drug development for parasitic diseases.

Keywords

COS Keywords:

Biochemistry, Biosynthesis, Drug Design, Infectious Diseases or Agents, Parasitology, Pathogenesis, Pharmacotherapy.

Additional Terms:

African Trypanosomiasis, Anti-parasitic Drugs, Chagas Disease, Drug Discovery, Glycolysis, Leishmania, Leishmaniasis, Parasitology, Protein Prenylation, Sterol Biosynthesis, Trypanosoma Brucei, Trypanosoma Cruzi.

Memberships

American Federation for Medical Research
American Society of Tropical Medicine and Hygiene
Infectious Diseases Society of America
Sigma Xi, The Scientific Research Society

Honors and Awards

2005, Member, Western Society for Clinical Investigation
2004, Philip and Helen Fialkow Scholar, School of Medicine, University of Washington
1994-1999, Physician Scientist Award, National Institutes of Health (NIH)
1991-1992, Chief Medical Resident, Minneapolis VA Medical Center, University of Minnesota
1988, Graduation with Honors, School of Medicine, University of Washington
1983, Magna cum laude, Princeton University, Princeton University
1983, Member, Sigma Xi

Funding Received

  • National Institutes of Health (NIH): Physician Scientist Award (K11), to .

Publications

  • Yokoyama K, Gillespie JR, Van Voorhis WC, Buckner FS, Gelb MH (Jan 2008) Protein geranylgeranyltransferase-I of Trypanosoma cruzi., Molecular and biochemical parasitology, 157 (1), 32-43 Abstract
  • Van Voorhis WC, Rivas KL, Bendale P, Nallan L, Hornéy C, Barrett LK, Bauer KD, Smart BP, Ankala S, Hucke O, Verlinde CL, Chakrabarti D, Strickland C, Yokoyama K, Buckner FS, Hamilton AD, Williams DK, Lombardo LJ, Floyd D, Gelb MH (Oct 2007) Efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of Plasmodium falciparum protein farnesyltransferase., Antimicrobial agents and chemotherapy, 51 (10), 3659-71 Abstract
  • Bendale P, Olepu S, Suryadevara PK, Bulbule V, Rivas K, Nallan L, Smart B, Yokoyama K, Ankala S, Pendyala PR, Floyd D, Lombardo LJ, Williams DK, Buckner FS, Chakrabarti D, Verlinde CL, Van Voorhis WC, Gelb MH (Sep 2007) Second generation tetrahydroquinoline-based protein farnesyltransferase inhibitors as antimalarials., Journal of medicinal chemistry, 50 (19), 4585-605 Abstract
  • Gillespie JR, Yokoyama K, Lu K, Eastman RT, Bollinger JG, Van Voorhis WC, Gelb MH, Buckner FS (Jun 2007) C-terminal proteolysis of prenylated proteins in trypanosomatids and RNA interference of enzymes required for the post-translational processing pathway of farnesylated proteins., Molecular and biochemical parasitology, 153 (2), 115-24 Abstract
  • Arakaki T, Neely H, Boni E, Mueller N, Buckner FS, Van Voorhis WC, Lauricella A, DeTitta G, Luft J, Hol WG, Merritt EA (Mar 2007) The structure of Plasmodium vivax phosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix., Acta crystallographica. Section F, Structural biology and crystallization communications, 63 (Pt 3), 178-82 Abstract
  • Mudeppa DG, Pang CK, Tsuboi T, Endo Y, Buckner FS, Varani G, Rathod PK (Feb 2007) Cell-free production of functional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase., Molecular and biochemical parasitology, 151 (2), 216-9 Abstract
  • Buckner FS (2007) Sterol 14-demethylase inhibitors for Trypanosoma cruzi infections, Drug Targets in Kinetoplastid Parasites, Georgetown, TX, Landes Biosciences (bookchapter)
  • Bosch J, Robien MA, Mehlin C, Boni E, Riechers A, Buckner FS, Van Voorhis WC, Myler PJ, Worthey EA, DeTitta G, Luft JR, Lauricella A, Gulde S, Anderson LA, Kalyuzhniy O, Neely HM, Ross J, Earnest TN, Soltis M, Schoenfeld L, Zucker F, Merritt EA, Fan E, Verlinde CL, Hol WG (Oct 2006) Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase., Journal of medicinal chemistry, 49 (20), 5939-46 Abstract
  • Glenn MP, Chang SY, Hornéy C, Rivas K, Yokoyama K, Pusateri EE, Fletcher S, Cummings CG, Buckner FS, Pendyala PR, Chakrabarti D, Sebti SM, Gelb M, Van Voorhis WC, Hamilton AD (Sep 2006) Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites., Journal of medicinal chemistry, 49 (19), 5710-27 Abstract
  • Phan BA, Laflamme MA, Stempien-Otero A, Limaye AP, Buckner FS, Levy WC (Sep 2006) Confirmation of Chagas' cardiomyopathy following heart transplantation., Heart and vessels, 21 (5), 325-7 Abstract
  • Mehlin C, Boni E, Buckner FS, Engel L, Feist T, Gelb MH, Haji L, Kim D, Liu C, Mueller N, Myler PJ, Reddy JT, Sampson JN, Subramanian E, Van Voorhis WC, Worthey E, Zucker F, Hol WG (Aug 2006) Heterologous expression of proteins from Plasmodium falciparum: results from 1000 genes., Molecular and biochemical parasitology, 148 (2), 144-60 Abstract
  • Robien MA, Bosch J, Buckner FS, Van Voorhis WC, Worthey EA, Myler P, Mehlin C, Boni EE, Kalyuzhniy O, Anderson L, Lauricella A, Gulde S, Luft JR, DeTitta G, Caruthers JM, Hodgson KO, Soltis M, Zucker F, Verlinde CL, Merritt EA, Schoenfeld LW, Hol WG (Mar 2006) Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 A resolution reveals intriguing extra electron density in the active site., Proteins, 62 (3), 570-7 Abstract
  • Holmes MA, Buckner FS, Van Voorhis WC, Mehlin C, Boni E, Earnest TN, DeTitta G, Luft J, Lauricella A, Anderson L, Kalyuzhniy O, Zucker F, Schoenfeld LW, Hol WG, Merritt EA (Mar 2006) Structure of the conserved hypothetical protein MAL13P1.257 from Plasmodium falciparum., Acta crystallographica. Section F, Structural biology and crystallization communications, 62 (Pt 3), 180-5 Abstract
  • Eastman RT, Buckner FS, Yokoyama K, Gelb MH, Van Voorhis WC (Feb 2006) Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation., Journal of lipid research, 47 (2), 233-40 Abstract
  • Hankins EG, Gillespie JR, Aikenhead K, Buckner FS (Nov 2005) Upregulation of sterol C14-demethylase expression in Trypanosoma cruzi treated with sterol biosynthesis inhibitors., Molecular and biochemical parasitology, 144 (1), 68-75 Abstract
  • Eastman RT, Barrett LK, Dupuis K, Buckner FS, Van Voorhis WC (Sep 2005) Leishmania inactivation in human pheresis platelets by a psoralen (amotosalen HCl) and long-wavelength ultraviolet irradiation., Transfusion, 45 (9), 1459-63 Abstract
  • Pang CK, De SK, White J, Buckner FS, Varani G, Rathod PK (Sep 2005) Differential drug binding by the highly conserved Plasmodium falciparum thymidylate synthase., Molecular and biochemical parasitology, 143 (1), 121-4 Abstract
  • Glenn MP, Chang SY, Hucke O, Verlinde CL, Rivas K, Hornéy C, Yokoyama K, Buckner FS, Pendyala PR, Chakrabarti D, Gelb M, Van Voorhis WC, Sebti SM, Hamilton AD (Aug 2005) Structurally simple farnesyltransferase inhibitors arrest the growth of malaria parasites., Angewandte Chemie (International ed. in English), 44 (31), 4903-6 Abstract
  • Hucke O, Gelb MH, Verlinde CL, Buckner FS (Aug 2005) The protein farnesyltransferase inhibitor Tipifarnib as a new lead for the development of drugs against Chagas disease., Journal of medicinal chemistry, 48 (17), 5415-8 Abstract
  • Buckner FS, Eastman RT, Yokoyama K, Gelb MH, Van Voorhis WC (Aug 2005) Protein farnesyl transferase inhibitors for the treatment of malaria and African trypanosomiasis., Current opinion in investigational drugs (London, England : 2000), 6 (8), 791-7 Abstract
  • Nallan L, Bauer KD, Bendale P, Rivas K, Yokoyama K, Hornéy CP, Pendyala PR, Floyd D, Lombardo LJ, Williams DK, Hamilton A, Sebti S, Windsor WT, Weber PC, Buckner FS, Chakrabarti D, Gelb MH, Van Voorhis WC (Jun 2005) Protein farnesyltransferase inhibitors exhibit potent antimalarial activity., Journal of medicinal chemistry, 48 (11), 3704-13 Abstract
  • Buckner FS, Wilson AJ (May 2005) Colorimetric assay for screening compounds against Leishmania amastigotes grown in macrophages., The American journal of tropical medicine and hygiene, 72 (5), 600-5 Abstract
  • Carrico D, Ohkanda J, Kendrick H, Yokoyama K, Blaskovich MA, Bucher CJ, Buckner FS, Van Voorhis WC, Chakrabarti D, Croft SL, Gelb MH, Sebti SM, Hamilton AD (Dec 2004) In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability., Bioorganic & medicinal chemistry, 12 (24), 6517-26 Abstract
  • Ohkanda J, Buckner FS, Lockman JW, Yokoyama K, Carrico D, Eastman R, de Luca-Fradley K, Davies W, Croft SL, Van Voorhis WC, Gelb MH, Sebti SM, Hamilton AD (Jan 2004) Design and synthesis of peptidomimetic protein farnesyltransferase inhibitors as anti-Trypanosoma brucei agents., Journal of medicinal chemistry, 47 (2), 432-45 Abstract
  • Buckner FS, Joubert BM, Boyle SM, Eastman RT, Verlinde CL, Matsuda SP (Dec 2003) Cloning and analysis of Trypanosoma cruzi lanosterol 14alpha-demethylase., Molecular and biochemical parasitology, 132 (2), 75-81 Abstract
  • Buckner F, Yokoyama K, Lockman J, Aikenhead K, Ohkanda J, Sadilek M, Sebti S, Van Voorhis W, Hamilton A, Gelb MH (Dec 2003) A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents., Proceedings of the National Academy of Sciences of the United States of America, 100 (25), 15149-53 Abstract
  • Hinshaw JC, Suh DY, Garnier P, Buckner FS, Eastman RT, Matsuda SP, Joubert BM, Coppens I, Joiner KA, Merali S, Nash TE, Prestwich GD (Sep 2003) Oxidosqualene cyclase inhibitors as antimicrobial agents., Journal of medicinal chemistry, 46 (20), 4240-3 Abstract
  • Gelb MH, Van Voorhis WC, Buckner FS, Yokoyama K, Eastman R, Carpenter EP, Panethymitaki C, Brown KA, Smith DF (Feb 2003) Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics., Molecular and biochemical parasitology, 126 (2), 155-63 Abstract
  • Buckner FS, Kateete DP, Lubega GW, Van Voorhis WC, Yokoyama K (Nov 2002) Trypanosoma brucei prenylated-protein carboxyl methyltransferase prefers farnesylated substrates., The Biochemical journal, 367 (Pt 3), 809-16 Abstract
  • Clerici F, Gelmi ML, Yokoyama K, Pocar D, Van Voorhis WC, Buckner FS, Gelb MH (Aug 2002) Isothiazole dioxides: synthesis and inhibition of Trypanosoma brucei protein farnesyltransferase., Bioorganic & medicinal chemistry letters, 12 (16), 2217-20 Abstract
  • Buckner FS, Eastman RT, Nepomuceno-Silva JL, Speelmon EC, Myler PJ, Van Voorhis WC, Yokoyama K, Cloning, heterologous expression, and substrate specificities of protein farnesyltransferases from Trypanosoma cruzi and Leishmania major, Molecular and Biochemical Parasitology, 122(2), 181-8, July 2002 Abstract
  • Hawn TR, Ozinsky A, Underhill DM, Buckner FS, Akira S, Aderem A (Jul 2002) Leishmania major activates IL-1 alpha expression in macrophages through a MyD88-dependent pathway., Microbes and infection / Institut Pasteur, 4 (8), 763-71 Abstract
  • Joubert BM, Nguyen LN, Matsuda SP, Buckner FS, Cloning and functional characterization of a Trypanosoma brucei lanosterol 14alpha-demethylase gene, Molecular and Biochemical Parasitology, 117(1), 115-7, September 2001 Abstract
  • Nepomuceno-Silva JL, Yokoyama K, de Mello LD, Mendonca SM, Paixao JC, Baron R, Faye JC, Buckner FS, Van Voorhis WC, Gelb MH, Lopes UG, TcRho1, a farnesylated Rho family homologue from Trypanosoma cruzi: cloning, trans-splicing, and prenylation studies, Journal of Biological Chemistry, 276(32), 29711-8, August 2001 Abstract
  • Bressi JC, Verlinde CL, Aronov AM, Shaw ML, Shin SS, Nguyen LN, Suresh S, Buckner FS, Van Voorhis WC, Kuntz ID, Hol WG, Gelb MH, Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design, Journal of Medicinal Chemistry, 44(13), 2080-93, June 2001 Abstract
  • Joubert BM, Buckner FS, Matsuda SP, Trypanosome and animal lanosterol synthases use different catalytic motifs, Organic Letters, 3(12), 1957-60, June 2001 Abstract
  • Buckner FS, Griffin JH, Wilson AJ, Van Voorhis WC, Potent anti-Trypanosoma cruzi activities of oxidosqualene cyclase inhibitors, Antimicrobial Agents and Chemotherapy, 45(4), 1210-5, April 2001 Abstract
  • Gelb MH, Buckner FS, Yokoyama K, Ohkanda J, Hamilton AD, Hguyen L, Rossi-Bergmann B, Sebti SM, Van Voorhis WC (2001) Protein prenylation in Trypanosomatids: a new piggy-back medicinal chemistry target for the development of agents against tropical diseases, Farnesyltransferase and Geranylgeranyltransferase-I: Targets for Cancer and Cardiovascular Therapy, Humana Press (bookchapter)
  • Bressi JC, Choe J, Hough MT, Buckner FS, Van Voorhis WC, Verlinde CL, Hol WG, Gelb MH, Adenosine analogues as inhibitors of Trypanosoma brucei phosphoglycerate kinase: elucidation of a novel binding mode for a 2-amino-N(6)-substituted adenosine, Journal of Medicinal Chemistry, 43(22), 4135-50, November 2000 Abstract
  • Buckner FS, Nguyen LN, Joubert BM, Matsuda SP, Cloning and heterologous expression of the Trypanosoma brucei lanosterol synthase gene, Molecular and Biochemical Parasitology, 110(2), 399-403, October 2000 Abstract
  • Buckner FS, Yokoyama K, Nguyen L, Grewal A, Erdjument-Bromage H, Tempst P, Strickland CL, Xiao L, Van Voorhis WC, Gelb MH, Cloning, heterologous expression, and distinct substrate specificity of protein farnesyltransferase from Trypanosoma brucei, Journal of Biological Chemistry, 275(29), 21870-6, 2000 Abstract
  • Buckner FS, Van Voorhis WC (2000) The immune response to Trypanosoma cruzi: control of infection and pathogenesis of Chagas' disease, Effects of Microbes in the Immune System, Philadelphia, Lippincott-Raven (bookchapter)
  • Aronov AM, Suresh S, Buckner FS, Van Voorhis WC, Verlinde CL, Opperdoes FR, Hol WG, Gelb MH, Structure-based design of submicromolar, biologically active inhibitors of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase, Proceedings of the National Academy of Sciences (USA), 96(8), 4273-8, April 1999 Abstract
  • Buckner FS, Wilson AJ, Van Voorhis WC, Detection of live Trypanosoma cruzi in tissues of infected mice by using histochemical stain for beta-galactosidase, Infection and Immunity, 67(1), 403-9, Jan 1999 Abstract
  • Buckner FS, Wilson AJ, White TC, Van Voorhis WC, Induction of resistance to azole drugs in Trypanosoma cruzi, Antimicrobial Agents and Chemotherapy, 42(12), 3245-50, December 1998 Abstract
  • Buckner FS, Wilson AJ, White TC, Van Voorhis WC, Induction of resistance to azole drugs in Trypanosoma cruzi., Antimicrobial Agents and Chemotherapy, 42(12), 3245-50, December 1998 Abstract
  • Yokoyama K, Trobridge P, Buckner FS, Van Voorhis WC, Stuart KD, Gelb MH, Protein farnesyltransferase from Trypanosoma brucei. A heterodimer of 61- and 65-kda subunits as a new target for antiparasite therapeutics, Journal of Biological Chemistry, 273(41), 26497-505, October 1998 Abstract
  • Yokoyama K, Trobridge P, Buckner FS, Scholten J, Stuart KD, Van Voorhis WC, Gelb MH, The effects of protein farnesyltransferase inhibitors on trypanosomatids: inhibition of protein farnesylation and cell growth, Molecular and Biochemical Parasitology, 94(1), 87-97, July 1998 Abstract
  • Buckner FS, Wipke BT, Van Voorhis WC, Trypanosoma cruzi infection does not impair major histocompatibility complex class I presentation of antigen to cytotoxic T lymphocytes, European Journal of Immunology, 27(10), 2541-8, October 1997 Abstract
  • Buckner FS, Wipke BT, Van Voorhis WC, Trypanosoma cruzi infection does not impair major histocompatibility complex class I presentation of antigen to cytotoxic T lymphocytes., European Journal of Immunology, 27(10), 2541-8, October 1997 Abstract
  • Buckner FS, Wilson AJ, Van Voorhis WC, Trypanosoma cruzi: use of herpes simplex virus-thymidine kinase as a negative selectable marker, Experimental Parasitology, 86(3), 171-80, July 1997 Abstract
  • Buckner FS, Verlinde CL, La Flamme AC, Van Voorhis WC, Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase, Antimicrobial Agents and Chemotherapy, 40(11), 2592-7, November 1996 Abstract
  • La Flamme AC, Buckner FS, Swindle J, Ajioka J, Van Voorhis WC, Trypanosoma cruzi: expression of interleukin-2 utilizing both supercoiled plasmids and linear DNAs, Experimental Parasitology, 83(1), 159-63, June 1996 Abstract
  • La Flamme AC, Buckner FS, Swindle J, Ajioka J, Van Voorhis WC, Expression of mammalian cytokines by Trypanosoma cruzi indicates unique signal sequence requirements and processing, Molecular and Biochemical Parasitology, 75(1), 25-31, December 1995 Abstract
  • Buckner FS, Pomeroy C, Cytomegalovirus disease of the gastrointestinal tract in patients without AIDS, Clinical Infectious Diseases, 17(4), 644-56, October 1993 Abstract
  • Buckner FS, Eschbach JW, Haley NR, Davidson RC, Adamson JW, Hypertension following erythropoietin therapy in anemic hemodialysis patients, American Journal of Hypertension, 3(12 Pt 1), 947-55, December 1990 Abstract
  • Buckner FS, Chen FN, Wade CE, Ganong WF, Centrally administered inhibitors of the generation and action of angiotensin II do not attenuate the increase in ACTH secretion produced by ether stress in rats, Neuroendocrinology, 42(2), 97-101, 1986 Abstract

Profile Details

Last Updated: 1/26/2008

COS Expertise ID #806101
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