Bio

Dr.Gabriel Oluga Aboge

Currently a lecturer at theDepartment of Public Health and Pharmacology of the University of Nairobi. He is involved in research and teaching of undergraduates and postgraduates in areas of general pharmacology and toxicology, molecular pharmacology and biochemical pharmacology. The primary research interests of Dr Aboge include application of molecular biotechnology strategies for drug discovery and development. Other areas of interest are basic research in molecular biology focusing on molecular diagnostics, basic molecular immunology and vaccine development.

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(Last updated: May 31, 2013)

Publications

2013

Shinuo Cao, Gabriel Oluga Aboge, MATMZYLLYYLYGKK.  2013.  Cloning, characterization and validation of inosine 5’-monophosphate dehydrogenase of Babesia gibsoni as molecular drug target. Parasitology International. 62(2013):87-94.dr._aboge_1.pdf
Masatani, T, Matsuo T, Tanaka T, Terkawi MA, Lee EG, Goo YK, Yamagishi J, Hayashi K, Kameyama K, Cao S, Nishikawa Y, Xuan X.  2013.  TgGRA23, a novel Toxoplasma gondii dense granule protein associated with the parasitophorous vacuole membrane and intravacuolar network. AbstractWebsite

Toxoplasma gondii is an intracellular protozoan parasite, which relies on a specialized compartment, the parasitophorous vacuole (PV), to survive within host cells. Dense granules within the parasite release a large variety of proteins to maintain the integrity of the vacuole structure. Here, we identified a novel dense granule protein in T. gondii, TgGRA23, which is a homolog of the Sarcocystis muris dense granule protein, SmDG32. Recombinant TgGRA23 (rTgGRA23) expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein was used to raise antisera in mice and rabbits. Immunoblotting showed that antisera from the immunized mice and rabbits reacted with parasite lysates to yield a 21-kDa native protein. In addition, immuno-electron microscopic examination showed that TgGRA23 resides in the dense granules, PV membrane and intravacuolar network of the parasite. To confirm the precise subcellular localization of TgGRA23 in T. gondii, an immunofluorescent antibody test was performed using dense granule markers. Notably, TgGRA23 co-localized with other dense granule proteins including TgGRA4 and TgGRA7, in the extracellular-stage parasites. Biochemical experiments indicated that TgGRA23 is insoluble and may form an electrostatic complex that is resistant to non-ionic detergents. Furthermore, specific antibodies to TgGRA23 were detected during the chronic stage of Toxoplasma infection in mice. Our results suggest that TgGRA23 is an as yet unknown member of the T. gondii dense granule proteins, and that it may be involved in remodeling or maintenance of the PV.

2012

Goo, Y-K, Aboge GO, Terkawi AM, Jia H, Yamagishi J, Sunaga F, Namikawa K, Cha S-Y, Jang H-K, Kim S, Nishikawa Y, Xuan X.  2012.  Four promising antigens, BgP32, BgP45, BgP47, and BgP50, for serodiagnosis of Babesia gibsoni infection were classified as B. gibsoni merozoite surface protein family. Abstract

We determined the molecular characteristics of four proteins, BgP32, BgP45, BgP47, and BgP50, of Babesia gibsoni. Localization by subcellular fractionations followed by Western blotting revealed that the corresponding native proteins belong to merozoite surface protein family of B. gibsoni (BgMSP). Moreover, antisera against either rBgP45 or rBgP47 cross-reacted with all the proteins of the BgMSP family on ELISA and IFAT analyses. Of the four candidate antigens, ELISA with rBgP45 yielded high sensitivity, and ELISA with rBgP32 resulted in high specificity and in concordance with IFAT results.
  2012.  Characterization of Babesia gibsoni pyruvate kinase as a novel drug target, 23rd March. Japanese Society for Parasitology . , Hyogo Medical School, Kobe, Japan
  2012.  Validating M17 leucineaminopeptidase of Babesia parasites as a molecular drug target, 16th sept. Japanese Society for Veterinary Sciences. , Iwate University, Morioka, Japan
  2012.  Study of 1-deoxy-D-xylulose 5 phosphate synthase and reductoisomerase enzymes of Babesia Parasites as molecular drug targets. Satellite Symposium for Japanese Society of Tropical Medicine. , Tokachi Plaza, Obihiro City, Japan

2011

  2011.  The demands of the developing world: Better animal health for food security in sub-Saharan Africa, 15th feb. Feeding the world . , London, United Kingdom
  2011.  Antifolates and their precursor molecules target dihydrofolatereductase-thymidylate synthase of Babesia gibsoni and inhibit parasite proliferation, 19th July. Society for Parasitology Conference. , Tokyo, Japan

2010

Aboge, GO, Terkawi M, Goo Y-K, Batbaatar V, Nishikawa Y, Sunaga F, Namikawa K, I I, Fujisaki K, Suzuki H, Xuan X.  2010.  Precursors of methotrexate target dihydrofolate reductase-thymidylate synthase of Babesia gibsoni. Abstract

It is not known whether precursors of methotrexate, such as 2, 4-diamino-6-hydroxymethyl-pteridine (DAP) and 2, 4-diamino-N10-methyl-pteroic acid (DAMPA), could target the dihydrofolate reductase-thymidylate synthase (DHFR-TS) enzyme of Babesia and inhibit the parasite growth. Therefore, we have determined whether DAP and DAMPA as well as other chemically related compounds like pteroic acid (PA) and N10Triflouropteroic acid (N10TFPA) could target the DHFR-TS enzyme of B. gibsoni and inhibit its growth. DAMPA was a more-potent inhibitor of the B. gibsoni growth in vitro (50% inhibition concentration [IC50] = 2.4 ± 0.20 μM) [mean ± standard error of the mean] than DAP (IC50 = 78 ± 15 μM). Moreover, DAMPA potently inhibited enzymatic activity of recombinant DHFR-TS of B. gibsoni (IC50 = 2.6 ± 0.15 μM) than DAP (IC50 > 100 μM). In contrast, PA and N10-TFPA did not inhibit the activity of the recombinant enzyme and growth of B. gibsoni. The inhibition of the recombinant enzyme activity by DAMPA mirrored with inhibition of the parasite growth indicating that the purified recombinant enzyme could be used for preliminary screening of some antifolate precursors. Therefore, both DAP and DAMPA inhibit growth of B. gibsoni by targeting the DHFR-TS enzyme of the parasite.
Goo, Y-K;, erkawi A;M, ia H;, Aboge O;G, Ooka H, Nelson B;, Kim S;, Sunaga F, Namikawa K;, Igarashi I.  2010.  Artesunate, a potential drug for treatment of Babesia infection. Abstract

The effects of artesunate, a water-soluble artemisinin derivative, against Babesia species, including Babesia bovis, Babesia gibsoni and Babesia microti were studied. Cultures of B. bovis and B. gibsoni were treated with 0.26, 2.6, 26 and 260 μM artesunate, showing inhibition of parasite growth at concentrations equal to and greater than 2.6 μM artesunate by days 3 post-treatment for B. gibsoni and B. bovis in a dose-dependent manner. Consistent with in vitro experiments, artesunate was effective in the treatment of mice infected with B. microti at doses equal to and greater than 10 mg/kg of body weight on days 8–10 post-infection. Taken together, these results suggest that artesunate could be a potential drug against Babesia infection.
  2010.  Biotechnology and Animal Health, 8-10th sept. 7th Biennial Scientific Conference & Exhibition. , University Of Nairobi, Kenya

2009

Terkawi, AM, Aboge G, Jia H, Goo Y-K, Ooka H, Yamagishi J, Nishikawa Y, Yokoyama N, Igarashi I, Kawazu S-I, Fujisaki K, Xuan X.  2009.  Molecular and immunological characterization of Babesia gibsoni. Abstract

Serological immune screening was used to identify a gene encoding heat shock protein-70 from Babesia gibsoni (BgHSP-70) that showed high homology with HSP-70s from other apicomplexan parasites. This gene corresponded to a full-length cDNA containing an open reading frame of 1968 bp predicted to result in a 70-kDa mature protein consisting of 656 amino acids. Analysis of the expression levels of BgHSP-70 indicated elevated transcription from cultured parasites incubated at 40C for 1 h, but not at 30C. Interestingly, antiserum raised against recombinant BgHSP-70 protein reacted specifically not only with a 70-kDa protein of B. gibsoni but also with a corresponding native protein of B. microti (BmHSP-70), indicating the high degree of conservation of this protein. The BmHSP-70 gene was then isolated and characterized and the immunoprotective properties of recombinant BgHSP-70 (rBgHSP-70) and rBmHSP-70 were compared in vitro and in vivo. Both proteins had potent mitogenic effects on murine and canine mononuclear cells as evidenced by high proliferative responses and IFN-c production after stimulation. Immunization regimes in BALB⁄c and C57BL⁄6 mice using rBgHSP-70 and rBmHSP-70 elicited high antibody levels, with concurrent significant reductions in peripheral parasitaemias. Taken together, these results emphasize the potential of HSP-70s as a molecular adjuvant vaccine
Zhang, H, Thekisoe OMM, Kyan H, Yamagishi J, Inoue N, Nishikawa Y, Zakimi S.  2009.  Toxoplasma gondii: Sensitive and rapid detection of infection by loop-mediated isothermal amplification (LAMP) method. Abstract

Loop-mediated isothermal amplification (LAMP) method amplifies DNA with high specificity, sensitivity and rapidity. In this study, we used a conserved sequence in the 200- to 300-fold repetitive 529 bp gene of Toxoplasma gondii to design primers for LAMP test. Detection limit of T. gondii LAMP assay with the primers is 1 pg/μL of T. gondii DNA, which was evaluated using 10-fold serially diluted DNA of cultured parasites. Furthermore, LAMP and conventional PCR methods were applied for amplification of the T. gondii DNA extracted from the lymph nodes taken from pigs which were suspected to be Toxoplasma infection. As a result, 76.9% (70/91) and 85.7% (78/91) of the samples were positive on PCR and LAMP analyzes, respectively. Therefore, the LAMP has a potential to be applied as an alternative molecular diagnostic tool for detection of T. gondii infection from veterinary samples. This is the first study, which applies the LAMP method to diagnose Toxoplasma from veterinary samples.
  2009.  Characterization of a leucine aminopeptidase of Babesia gibsoni.

2008

  2008.  loning, Expression, and Characterization of Babesia gibsoni Dihydrofolate Reductase-Thymidylate Synthase: Inhibitory Effect of Antifolates on Its Catalytic Activity and Parasite Proliferation. Department of Public Health Pharmacology and Toxicology.
  2008.  C3 contributes to the cross-protective immunity induced by Babesia gibsoni phosphoribo protein P0 against a lethal B. rodhaini infection.
  2008.  Babesia gibsoni: Serodiagnosis of infection in dogs by an enzyme-linked immunosorbent assay with recombinant BgTRAP. Experimental Parasitology 1. 118(2008):555-560.
  2008.  Babesia gibsoni: Identification of an immunodominant, interspersed repeat antigen.
  2008.  Antifolate drugs target dihydrofolatereductase-thymidylate synthase of Babesia gibsoni, 2008. The 146th Japanese Society of Veterinary Science (JSVS) Symposium. , Japan

2007

Aboge, GO, Jia H, Kuriki H, Zhou J, Nishikawa Y, Igarashi I, Fujisaki K, Suzuki H, Xuan X.  2007.  Molecular characterization of a novel 32-kDa merozoite antigen of Babesia gibsoni with a better diagnostic performance by enzyme-linked immunosorbent assay. Abstract

We cloned and expressed 3 novel gene encoding a 32-kDa merozoite protein of Babesia gibsoni (BgP32). The length of nucleotide sequence of the cD;\' A \\'3. 1-1-6-1 bp with an open reading frame of 969 bp. The truncated recombinant BgP32 (rBgP32) without a signal peptide and Cvterrninal hydrophobic sequence was expressed in Escherichia coli as a oluble glutathione- -rran ferase (GST) fusion protein. We stern blotting demonstrated that the native protein was 32-kDa, consistent with molecular weight of thc predicted mature polypeptide. Enzyme-linked irnmunosorbent assay (ELISA) using rBgP32 detected specific antibodi s from 8 days to 541 days post-infection in the sequential sera from a dog experimentally infected wirh B. gibsoni. Moreover. the antigen did not cross-react with B. canis subspecies and closely related protozoan parasites, indicating that rBgP32 is a specific diagnostic antigen. Analysis of 47 era taken from dogs with anaemic signs re ealed that rBgP32 detected a higher proportion of B. gibson! seroposirive sample' (77%) than its previou Iy identified rBgPSO (68%) homologue. These results indicate that the BgP32 is a novel immunodominant antigen of B. gibsoni, and rBgP32 might be useful for diagno is of B. gibsoni infection
Aboge, GO, Jia H, Goo Y, Kuriki K, Nishikawa Y, Igarashi I, Suzuki H, Xuan X.  2007.  A novel 57-kDa merozoite protein of Babesia gibsoni is a prospective antigen for diagnosis and serosurvey of canine babesiosis by enzyme-linked immunosorbent assay. Abstract

We isolated a novel single copy gene encoding a 57-kDa merozoite protein of Babesia gibsoni (BgP57). The nucleotide sequence of the cDNA was 2387 bp with an open reading frame (ORP) of 1644 bp encoding a 57-kDa predicted polypeptide having 547 amino acid residues. The recombinant BgP57 (rBgP57) without a predicted signal peptide was expressed in Escherichia coli as a soluble glutathione S-transferase (GST) fusion protein. Western blotting showed that the corresponding native protein was 57-kDa, consistent with molecular weight of predicted mature polypeptide. An indirect enzyme-linked immunosorbent assay (ELISA) using the rBgP57 detected specific antibodies in the sequential sera from a dog experimentally infected with B. gibsoni. Moreover, the antigen did not cross-react with antibodies to B. canis sub-species and closely related apicomplexan parasites indicating that the rBgP57 was a specific antigen for B. gibsoni antibodies. The diagnostic performance of ELISA based on rBgP57 using 107 sera from B. gibsoni-naturally infected dogs was the same as the previously identified rBgP32 but performed better than the previously studied rBgP50. Although, seminested peR detected higher proportions (82%) of positive samples than the ELISAs, the Mcnemar's chi-square test showed that there was no significant difference in relative effectiveness of rBgP57-ELISA and seminested peR (x2 = 2.70; P = 0.1003) in identifying positive samples. The rBgP57-ELISA when used in combination with rBgP32-ELISA and rBgP50-ELISA appeared to improve sensitivity of the rBgP57-ELISA for detection of B. gibsoni antibodies. Overall, the rBgP57-ELISA and seminested peR when used in combination, could improve epidemiological surveys and clinical diagnosis of B. gibsoni infection.

2002

Koech, R, Koroti E, Aboge G, Mwangi A, Odhiambo J;, Ouma E;, Staal S;, McDermott J;, Kangethe E;, Arimi S;, Omore A.  2002.  Assessing and managing milk-borne health risks for the benefit of consumers in Kenya.

2000

Aboge, GO;, Kang’ethe EK;, Arimi SM;, Omore AO;, McDermott JJ;, Kanja LW;, Macharia JK;, Nduhiu JG;, Githua A.  2000.  Antimicrobial Agents Detected In Marketed Milk In Kenya. Abstract

Drug residues in foods are a major public health concern in many countries, especially where most food sales bypass official quality assurance channels. In common with many tropical countries, sales of unpasteurized milk in Kenya account for over 85% of marketed milk. This milk is either sold directly from producers to consumers or via various cadres of informal market agents. Besides residues that may arise from lack of adherence to withdrawal times following cow therapy, there have been concerns that some antimicrobial agents may be added to informally marketed milk to extend its shelf life. As part of a large study to assess public health hazards associated with marketed milk, samples were collected seasonally between January 1999 and January 2000 from raw (unpasteurized) milk consuming households and informal market agents of various cadres. Pasteurised milk samples were also collected from retail points and tested for comparison. All samples were screened for antimicrobial residues using charm AIM-96 and Charm-ROSA (Charm Sciences Inc, USA) tests. The former detects a wide range of anti-microbials, and the latter detects β-lactams and tetracyclines specifically, at levels above maximum residue limits (MRLS) recommended by the European Union (EU). The Charm-AIM screening test showed that 9.4% and 5.7% of samples from consumer households and market agents had antimicrobial residues above EU MRLS, respectively. It was concluded that antimicrobial residues were more likely to have originated at farm-level than because of poor market handling practices.

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