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4. CAVE VODOU IN HAITI: THE USE OF CAVES AS SACRED SPACE IN MODERN HAITIAN RITUAL

Author

Wilkinson, Patrick Richard

Subjects
Cultural anthropology, Archaeology, Caribbean studies, Cave, Haiti, Vodou
Abstract

Haitian Vodou is a syncretic religion that combines elements of West African beliefs and indigenous Taíno culture with a rigid framework of forced Catholicism. Western cultures have always been fascinated by, yet fearful of, Vodou and commonly depict it as devil-worship and witchcraft. It is in large part due to this pervasive view of Vodou in Haiti, as well as the challenging conditions that come with working in Haiti, that little academic interest has been paid to the nuances of the modern practice of Vodou, particularly the use of caves. In this dissertation, I incorporate ethnographic and archaeological methods to present the first comprehensive study of how modern Vodou practitioners across Haiti have incorporated caves into their syncretic ritual repertoire.Through interviews, observation, participation, and an assessment of the ephemeral material remains left behind by Vodou practitioners, I describe what forms and purposes these rituals take, determine which parts of caves are associated with different aspects of Vodou, and compare the demographics of cave practitioners to those of Vodou practitioners in general. I argue that while Vodou, as it is practiced in public and at home, follows the definitions of religion, the aspects of Vodou as it is practiced in caves are more in line with definitions of magic, and I propose three reasons for this. This research has two purposes. First, it is an ethno-archaeological study intended to fill in gaps in the academic body of work regarding Vodou in Haiti where cave usage has been ignored. As ethnography, it has the potential to inform not just academics, but a broader audience, and to correct misconceptions regarding Vodou in particular and Haiti in general. Second, this project may be of use to archaeologists, particularly those who work in caves or other ritual spaces, whose data may be influenced by the activities of past caretakers. Every cave that in this study had some form of active caretaker and the model of caretaker presented in this study may be of use in interpreting archaeological sites that share a similar economic and social structure to modern Haiti.

Published
2019

5. Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine

Author

Gigoux, Mathieu, primary, Holmström, Morten O., additional, Zappasodi, Roberta, additional, Park, Joseph J., additional, Pourpe, Stephane, additional, Bozkus, Cansu Cimen, additional, Mangarin, Levi M. B., additional, Redmond, David, additional, Verma, Svena, additional, Schad, Sara, additional, George, Mariam M., additional, Venkatesh, Divya, additional, Ghosh, Arnab, additional, Hoyos, David, additional, Molvi, Zaki, additional, Kamaz, Baransel, additional, Marneth, Anna E., additional, Duke, William, additional, Leventhal, Matthew J., additional, Jan, Max, additional, Ho, Vincent T., additional, Hobbs, Gabriela S., additional, Knudsen, Trine Alma, additional, Skov, Vibe, additional, Kjær, Lasse, additional, Larsen, Thomas Stauffer, additional, Hansen, Dennis Lund, additional, Lindsley, R. Coleman, additional, Hasselbalch, Hans, additional, Grauslund, Jacob H., additional, Lisle, Thomas L., additional, Met, Özcan, additional, Wilkinson, Patrick, additional, Greenbaum, Benjamin, additional, Sepulveda, Manuel A., additional, Chan, Timothy, additional, Rampal, Raajit, additional, Andersen, Mads H., additional, Abdel-Wahab, Omar, additional, Bhardwaj, Nina, additional, Wolchok, Jedd D., additional, Mullally, Ann, additional, and Merghoub, Taha, additional

Published
2022
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6. Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine

Author

Gigoux, Mathieu, Holmström, Morten O., Zappasodi, Roberta, Park, Joseph J., Pourpe, Stephane, Bozkus, Cansu Cimen, Mangarin, Levi M.B., Redmond, David, Verma, Svena, Schad, Sara, George, Mariam M., Venkatesh, Divya, Ghosh, Arnab, Hoyos, David, Molvi, Zaki, Kamaz, Baransel, Marneth, Anna E., Duke, William, Leventhal, Matthew J., Jan, Max, Ho, Vincent T., Hobbs, Gabriela S., Knudsen, Trine Alma, Skov, Vibe, Kjær, Lasse, Larsen, Thomas Stauffer, Hansen, Dennis Lund, Lindsley, R. Coleman, Hasselbalch, Hans, Grauslund, Jacob H., Lisle, Thomas L., Met, Özcan, Wilkinson, Patrick, Greenbaum, Benjamin, Sepulveda, Manuel A., Chan, Timothy, Rampal, Raajit, Andersen, Mads H., Abdel-Wahab, Omar, Bhardwaj, Nina, Wolchok, Jedd D., Mullally, Ann, Merghoub, Taha, Gigoux, Mathieu, Holmström, Morten O., Zappasodi, Roberta, Park, Joseph J., Pourpe, Stephane, Bozkus, Cansu Cimen, Mangarin, Levi M.B., Redmond, David, Verma, Svena, Schad, Sara, George, Mariam M., Venkatesh, Divya, Ghosh, Arnab, Hoyos, David, Molvi, Zaki, Kamaz, Baransel, Marneth, Anna E., Duke, William, Leventhal, Matthew J., Jan, Max, Ho, Vincent T., Hobbs, Gabriela S., Knudsen, Trine Alma, Skov, Vibe, Kjær, Lasse, Larsen, Thomas Stauffer, Hansen, Dennis Lund, Lindsley, R. Coleman, Hasselbalch, Hans, Grauslund, Jacob H., Lisle, Thomas L., Met, Özcan, Wilkinson, Patrick, Greenbaum, Benjamin, Sepulveda, Manuel A., Chan, Timothy, Rampal, Raajit, Andersen, Mads H., Abdel-Wahab, Omar, Bhardwaj, Nina, Wolchok, Jedd D., Mullally, Ann, and Merghoub, Taha

Abstract

The majority of JAK2V617F-negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin (CALR), resulting in a common carboxyl-terminal mutant fragment (CALRMUT), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALRMUT-specific T cells are rare in patients with CALRMUT MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALRMUT MPN from two independent cohorts. We observed that MHC-I alleles that present CALRMUT neoepitopes with high affinity are underrepresented in patients with CALRMUT MPN. We speculated that this was due to an increased chance of immune-mediated tumor rejection by individuals expressing one of these MHC-I alleles such that the disease never clinically manifested. As a consequence of this MHC-I allele restriction, we reasoned that patients with CALRMUT MPN would not efficiently respond to a CALRMUT fragment cancer vaccine but would when immunized with a modified CALRMUT heteroclitic peptide vaccine approach. We found that heteroclitic CALRMUT peptides specifically designed for the MHC-I alleles of patients with CALRMUT MPN efficiently elicited a CALRMUT cross-reactive CD8+ T cell response in human peripheral blood samples but not to the matched weakly immunogenic CALRMUT native peptides. We corroborated this effect in vivo in mice and observed that C57BL/6J mice can mount a CD8+ T cell response to the CALRMUT fragment upon immunization with a CALRMUT heteroclitic, but not native, peptide. Together, our data emphasize the therapeutic potential of heteroclitic peptide–based cancer vaccines in patients with CALRMUT MPN.

Published
2022

10. Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice

Author

Veglia, Filippo, primary, Hashimoto, Ayumi, additional, Dweep, Harsh, additional, Sanseviero, Emilio, additional, De Leo, Alessandra, additional, Tcyganov, Evgenii, additional, Kossenkov, Andrew, additional, Mulligan, Charles, additional, Nam, Brian, additional, Masters, Gregory, additional, Patel, Jaymala, additional, Bhargava, Vipul, additional, Wilkinson, Patrick, additional, Smirnov, Denis, additional, Sepulveda, Manuel A., additional, Singhal, Sunil, additional, Eruslanov, Evgeniy B., additional, Cristescu, Razvan, additional, Loboda, Andrey, additional, Nefedova, Yulia, additional, and Gabrilovich, Dmitry I., additional

Published
2021
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12. SLC25A34 regulates bioenergetic metabolism in the murine liver

Author

Roy, Nairita, primary, May, Meredith, additional, Delgado, Evan Ryan, additional, Alencastro, Frances, additional, Wilkinson, Patrick David, additional, Smyers, Mei, additional, Reynolds, Michael John, additional, Shiva, Sruti, additional, and Duncan, Andrew Wayne, additional

Published
2020
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15. Polyploidy in Liver Regeneration and Adaptation to Chronic Injury

Author

Wilkinson, Patrick D., primary, Delgado, Evan R., additional, Alencastro, Frances, additional, Leek, Madeleine P., additional, Roy, Nairita, additional, Weirich, Matthew P., additional, Stahl, Elizabeth C., additional, Otero, P. Anthony, additional, Chen, Maelee I., additional, Brown, Whitney K., additional, Oertel, Michael, additional, and Duncan, Andrew W., additional

Published
2019
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16. Polyploidy in Liver Regeneration and Adaptation to Chronic Liver Injury

Author

Wilkinson, Patrick and Wilkinson, Patrick

Abstract

The liver contains diploid and polyploid hepatocytes (tetraploid, octaploid, etc.), with polyploids comprising ≥90% of the hepatocyte population in adult mice. Moreover, polyploid hepatocytes form multipolar spindles in mitosis, leading to individual chromosome gains and/or losses and random aneuploidy. The molecular mechanisms that regulate polyploidization have been well-characterized; however, it is unclear if diploid and polyploid hepatocytes function similarly in multiple contexts. The effect of aneuploidy on liver function is also unknown and the degree of liver aneuploidy is debated, with reports showing aneuploidy affects 5-60% of hepatocytes. We used mice lacking E2f7 and E2f8 in the liver (LKO), which have a polyploidization defect. We found diploid hepatocytes were enriched 20-fold in LKO livers and nearly all LKO hepatocytes were euploid compared to control hepatocytes, which were mostly aneuploid, suggesting polyploids are required for production of aneuploid progeny. Livers from LKO mice maintained normal function but became highly tumorigenic when challenged with tumor-promoting stimuli, suggesting that tumors in LKO mice were driven, at least in part, by diploid hepatocytes capable of rapid proliferation. Indeed, LKO hepatocytes were more proliferative and out-competed control hepatocytes in competitive repopulation studies. To eliminate potentially confounding effects associated with E2f7/E2f8 deficiency, diploid and polyploid hepatocytes from wild-type mice were examined. The wild-type diploid cells also showed a proliferative advantage, entering and progressing through the cell cycle faster than polyploid cells, both in vitro and during liver regeneration. Finally, to investigate the role of diploids and polyploids in chronic injury we bred LKO mice onto a tyrosinemia background, a disease model where the liver can develop disease-resistant, regenerative nodules. Survival was significantly reduced in tyrosinemic LKO mice, compared to controls, but

Published
2019

18. Differential Roles for Diploid and Polyploid Hepatocytes in Acute and Chronic Liver Injury.

Author

Wilkinson, Patrick D. and Duncan, Andrew W.

Subjects
*LIVER cells, *LIVER injuries, *LIVER regeneration, *SOMATIC cells, *POLYPLOIDY
Abstract

Hepatocytes are the primary functional cells of the liver that perform essential roles in homeostasis, regeneration, and injury. Most mammalian somatic cells are diploid and contain pairs of each chromosome, but there are also polyploid cells containing additional sets of chromosomes. Hepatocytes are among the best described polyploid cells, with polyploids comprising more than 25 and 90% of the hepatocyte population in humans and mice, respectively. Cellular and molecular mechanisms that regulate hepatic polyploidy have been uncovered, and in recent years, diploid and polyploid hepatocytes have been shown to perform specialized functions. Diploid hepatocytes accelerate liver regeneration induced by resection and may accelerate compensatory regeneration after acute injury. Polyploid hepatocytes protect the liver from tumor initiation in hepatocellular carcinoma and promote adaptation to tyrosinemia-induced chronic injury. This review describes how ploidy variations influence cellular activity and presents a model for context-specific functions for diploid and polyploid hepatocytes. [ABSTRACT FROM AUTHOR]

Published
2021
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19. Abstract 3813: Development of JNJ-64164711, a low fucose anti-GITR antibody for enhanced depletion of tumor regulatory T cells (Tregs)

Author

Holland, Cam V., primary, Kehoe, John, additional, Hailey, Judith, additional, Nanjunda, Rupesh, additional, Lacy, Eilyn, additional, Ernst, Robin, additional, Zhang, Di, additional, Wu, Sam, additional, Teplyakov, Alexey, additional, Li, Weimin, additional, Kinder, Michelle, additional, Thompson, Edward W., additional, Wilkinson, Patrick, additional, Wong, Jackson, additional, Chu, Gerald, additional, Okonkwo, Linda, additional, Alvarez, John D., additional, Nguyen, Anhco, additional, Grewal, Iqbal S., additional, Chatterjee-Kishore, Moitreyee, additional, Salvati, Mark, additional, and Gottardis, Marco, additional

Published
2018
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21. RORγt and RORα signature genes in human Th17 cells

Author

Castro, Glenda, primary, Liu, Xuejun, additional, Ngo, Karen, additional, De Leon-Tabaldo, Aimee, additional, Zhao, Shanrong, additional, Luna-Roman, Rosa, additional, Yu, Jingxue, additional, Cao, Tinghua, additional, Kuhn, Robert, additional, Wilkinson, Patrick, additional, Herman, Krystal, additional, Nelen, Marina I., additional, Blevitt, Jonathan, additional, Xue, Xiaohua, additional, Fourie, Anne, additional, and Fung-Leung, Wai-Ping, additional

Published
2017
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22. Polyploid Hepatocytes Facilitate Adaptation and Regeneration to Chronic Liver Injury

Author

Wilkinson, Patrick D., Alencastro, Frances, Delgado, Evan R., Leek, Madeleine P., Weirich, Matthew P., Otero, P. Anthony, Roy, Nairita, Brown, Whitney K., Oertel, Michael, and Duncan, Andrew W.

Abstract

The liver contains diploid and polyploid hepatocytes (tetraploid, octaploid, etc.), with polyploids comprising ≥90% of the hepatocyte population in adult mice. Polyploid hepatocytes form multipolar spindles in mitosis, which lead to chromosome gains/losses and random aneuploidy. The effect of aneuploidy on liver function is unclear, and the degree of liver aneuploidy is debated, with reports showing aneuploidy affects 5% to 60% of hepatocytes. To study relationships among liver polyploidy, aneuploidy, and adaptation, mice lacking E2f7and E2f8in the liver (LKO), which have a polyploidization defect, were used. Polyploids were reduced fourfold in LKO livers, and LKO hepatocytes remained predominantly diploid after extensive proliferation. Moreover, nearly all LKO hepatocytes were euploid compared with control hepatocytes, suggesting polyploid hepatocytes are required for production of aneuploid progeny. To determine whether reduced polyploidy impairs adaptation, LKO mice were bred onto a tyrosinemia background, a disease model whereby the liver can develop disease-resistant, regenerative nodules. Although tyrosinemic LKO mice were more susceptible to morbidities and death associated with tyrosinemia-induced liver failure, they developed regenerating nodules similar to control mice. Analyses revealed that nodules in the tyrosinemic livers were generated by aneuploidy and inactivating mutations. In summary, we identified new roles for polyploid hepatocytes and demonstrated that they are required for the formation of aneuploid progeny and can facilitate adaptation to chronic liver disease.

Published
2024
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