PATRICK JACK SPENCER
Resumo
Possui graduação em Ciências Biológicas pela Universidade Presbiteriana Mackenzie (1991), mestrado em Tecnologia Nuclear pela Universidade de São Paulo (1995) e doutorado em Tecnologia Nuclear pela Universidade de São Paulo (2000) tendo sido bolsista sandwich no US Army Medical Research Institute for Infeccious Diseases (98-99). É responsável pelo Biotério de criação e manutenção de animais de laboratório do IPEN. Tem experiência na área de Bioquímica, com ênfase em Proteínas, atuando principalmente nos seguintes temas: veneno, proteínas, bothrops, irradiação e miotoxina.(Texto extraído do Currículo Lattes em 22 dez. 2021)
Projetos de Pesquisa
Unidades Organizacionais
Cargo
38 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 38
Artigo IPEN-doc 29689 Anti-Metalloproteases2023 - GODOI, KEMILY S. de; GUIDOLIN, FELIPE R.; PORTARO, FERNANDA C.V.; SPENCER, PATRICK J.; SILVA, WILMAR D. daBitis arietans is a medically important snake found in Sub-Saharan Africa. The envenomation is characterized by local and systemic effects, and the lack of antivenoms aggravates the treatment. This study aimed to identify venom toxins and develop antitoxins. The F2 fraction obtained from Bitis arietans venom (BaV) demonstrated the presence of several proteins in its composition, including metalloproteases. Titration assays carried out together with the immunization of mice demonstrated the development of anti-F2 fraction antibodies by the animals. The determination of the affinity of antibodies against different Bitis venoms was evaluated, revealing that only BaV had peptides recognized by anti-F2 fraction antibodies. In vivo analyses demonstrated the hemorrhagic capacity of the venom and the effectiveness of the antibodies in inhibiting up to 80% of the hemorrhage and 0% of the lethality caused by BaV. Together, the data indicate: (1) the prevalence of proteins that influence hemostasis and envenomation; (2) the effectiveness of antibodies in inhibiting specific activities of BaV; and (3) isolation and characterization of toxins can become crucial steps in the development of new alternative treatments. Thus, the results obtained help in understandArtigo IPEN-doc 29112 Antibodies as snakebite antivenoms2022 - SILVA, WILMAR D. da; ANDRADE, SONIA A. de; MEGALE, ANGELA A.A.; SOUZA, DANIEL A. de; SANTANNA, OSVALDO A.; MAGNOLI, FABIO C.; GUIDOLIN, FELIPE R.; GODOI, KEMILY S.; SALADINI, LUCAS Y.; SPENCER, PATRICK J.; PORTARO, FERNANDA C.V.Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab’)2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.Capítulo IPEN-doc 28624 Bradykinin-potentiating and related peptides from reptile venoms2021 - PIMENTA, DANIEL C.; SPENCER, PATRICK J.Evolution has provided venomous snakes with a vast arsenal of molecules able to interfere in several physiological processes. The ultimate role of these toxins, which are proteins or peptides, is to subdue the prey, although digestive functions should also be considered. Among these toxins, some are vasoactive peptides, which induce a drastic drop in blood pressure. This effect is attributed mostly to bradykinin-potentiating peptides, although other venom peptides have been shown to interfere with blood pressure. Bradykinin-potentiating peptides are modular in nature, with highly conserved motifs, and present high proline content, a pyroglutamate at the N-terminal and an IPP motif at the C-terminal. These peptides are potent and highly selective inhibitors of angiotensin-converting enzyme, a crucial molecule for blood pressure regulation, and display K i s as low as 8 nM. Besides the enzyme inhibition, some of these peptides might cross the cell membrane, interfering in the production of nitric oxide, another modulator of blood vessel tonus. Evolution frequently results in physiological redundancies. Such a fact is reflected by the occurrence of another class of blood pressure–modulating toxins. C-type natriuretic peptides can be considered as such. Apparently, these toxins increase guanylate cyclase levels, inducing vasorelaxation. These peptides are being considered as drug leads for congestive heart failure. While C-type natriuretic peptides are still under investigation as potential drugs, bradykinin-potentiating peptide–derived drugs are the boldest example of the use of a deleterious “toxin” as a building block for a cheap drug that benefits a huge number of human beings.Artigo IPEN-doc 27113 Molecular model of cytotoxin-1 from Naja mossambica mossambica venom in complex with chymotrypsin2015 - MUNAWAR, AISHA; AKREM, AHMED; HUSSAIN, ASHIQ; SPENCER, PATRICK; BETZEL, CHRISTIANSnake venom is a myriad of biologically active proteins and peptides. Three finger toxins are highly conserved in their molecular structure, but interestingly possess diverse biological functions. During the course of evolution the introduction of subtle mutations in loop regions and slight variations in the three dimensional structure, has resulted in their functional versatility. Cytotoxin-1 (UniProt ID: P01467), isolated from Naja mossambica mossambica, showed the potential to inhibit chymotrypsin and the chymotryptic activity of the 20S proteasome. In the present work we describe a molecular model of cytotoxin- 1 in complex with chymotrypsin, prepared by the online server ClusPro. Analysis of the molecular model shows that Cytotoxin-1 (P01467) binds to chymotrypsin through its loop I located near the N-terminus. The concave side of loop I of the toxin fits well in the substrate binding pocket of the protease. We propose Phe10 as the dedicated P1 site of the ligand. Being a potent inhibitor of the 20S proteasome, cytotoxin-1 (P01467) can serve as a potential antitumor agent. Already snake venom cytotoxins have been investigated for their ability as an anticancer agent. The molecular model of cytotoxin-1 in complex with chymotrypsin provides important information towards understanding the complex formation.Resumo IPEN-doc 22122 Estudo dos efeitos da radiação gama de sup(Co na bothropstoxina 1 do veneno de Bothrops jararacussu2007 - SILVA, DIEGO de A.; SILVA, MURILO C. da; SPENCER, PATRICK J.Resumo IPEN-doc 21477 Isolamento das toxinas do veneno de Crotalus durissus terrificus2015 - FERNANDES, MARINA G.; SPENCER, PATRICK J.Artigo IPEN-doc 21327 Venomics of the Australian eastern brown snake (Pseudonaja textilis): Detection of new venom proteins and splicing variants2015 - VIALA, VINCENT L.; HILDEBRAND, DIANA; TRUSCH, MARIA; FUCASE, TAMARA M.; SCIANI, JULIANA M.; PIMENTA, DANIEL C.; ARNI, RAGHUVIR K.; SCHLUTER, HARTMUT; BETZEL, CHRISTIAN; MIRTSCHIM, PETER; DUNSTAN, NATHAN; SPENCER, PATRICK J.Artigo IPEN-doc 21288 Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins2015 - VIALA, VINCENT L.; HILDEBRAND, DIANA; FUCASE, TAMARA M.; SCIANI, JULIANA M.; PREZOTTO NETO, JOSE P.; RIEDNER, MARIA; SANCHES, LEONARDO; NISHIMURA, PAULA J.; OGUIURA, NANCY; PIMENTA, DANIEL C.; SCHLUTER, HARTMUT; BETZEL, CHRISTIAN; ARNI, RAGHUVIR K.; SPENCER, PATRICK J.Artigo IPEN-doc 20886 New insights into the structural characteristics of irradiated crotamine2015 - OLIVEIRA, KARINA C.; SPENCER, PATRICK J.; FERREIRA JUNIOR, RUI S.; NASCIMENTO, NANCIArtigo IPEN-doc 20303 Pseudechis guttatus venom proteome: Insights into evolution and toxin clustering2014 - VIALA, VINCENT L.; HILDEBRAND, DIANA; TRUSCH, MARIA; ARNI, RAGHUVIR K.; PIMENTA, DANIEL C.; SCHLUTER, HARTMUT; BETZEL, CHRISTIAN; SPENCER, PATRICK J.