Oliver Pearce - Academia.edu (original) (raw)

Papers by Oliver Pearce

The various systems of public redress allow citizens to seek remedies for what they perceive to b... more The various systems of public redress allow citizens to seek remedies for what they perceive to be poor treatment, mistakes, faults or injustices in their dealings with departments or agencies. They are the arrangements for getting things put right, remedying grievances, securing a second view or appealing a disputed decision and, where compensation is appropriate, the means through which this can be sought.

Cancer research, Jan 16, 2015

The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experim... more The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here we show that IL-6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL-6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared to VEGF-stimulated vessels. The mechanism of IL-6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as Angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL-6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies there was an association between levels of IL-6mRNA, Jagged1 and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL-6 and for understanding abnormal angiogenesis in canc...

OncoImmunology, 2014

We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor pro... more We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor progression, dependent upon the dosage used. The narrow range over which this immune response curve (IRC) occurs is surprising. Here we discuss features of the IRC, the mechanisms identified so far, and the potential clinical implications.

The Journal of biological chemistry, Jan 6, 2015

As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expr... more As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac, was demonstrated. PolySia is known to modulate cell adhesion, migration and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor (BDNF) normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc caused resistance to Neu1 induced polySia turnover, and also inhibited the associated release of BDNF. These results indicate the importance of rapid turnover of the polySia g...

Proceedings of the National Academy of Sciences of the United States of America, Jan 24, 2015

Atlas of the oral and maxillofacial surgery clinics of North America, 2015

The effective and efficient management of a patient with a neck mass in a 1-stop clinic requires ... more The effective and efficient management of a patient with a neck mass in a 1-stop clinic requires a collaborative and harmonious partnership among surgeon, radiologist, and pathologist. In this article, theoretic and practical issues are addressed to optimize patient care when prescribing, planning, performing, and interpreting imaging for neck disease.

Oncoimmunology, 2014

We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor pro... more We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor progression, dependent upon the dosage used. The narrow range over which this immune response curve (IRC) occurs is surprising. Here we discuss features of the IRC, the mechanisms identified so far, and the potential clinical implications.

Proceedings of the National Academy of Sciences of the United States of America, Jan 30, 2014

Certain pathogenic bacteria are known to modulate the innate immune response by decorating themse... more Certain pathogenic bacteria are known to modulate the innate immune response by decorating themselves with sialic acids, which can engage the myelomonocytic lineage inhibitory receptor Siglec-9, thereby evading immunosurveillance. We hypothesized that the well-known up-regulation of sialoglycoconjugates by tumors might similarly modulate interactions with innate immune cells. Supporting this hypothesis, Siglec-9-expressing myelomonocytic cells found in human tumor samples were accompanied by a strong up-regulation of Siglec-9 ligands. Blockade of Siglec-9 enhanced neutrophil activity against tumor cells in vitro. To investigate the function of inhibitory myelomonocytic Siglecs in vivo we studied mouse Siglec-E, the murine functional equivalent of Siglec-9. Siglec-E-deficient mice showed increased in vivo killing of tumor cells, and this effect was reversed by transgenic Siglec-9 expression in myelomonocytic cells. Siglec-E-deficient mice also showed enhanced immunosurveillance of au...

Proceedings of the National Academy of Sciences, 2014

A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term co... more A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term consumption of "red meat" of mammalian origin. Although multiple theories have attempted to explain this human-specific association, none have been conclusively proven. We used an improved method to survey common foods for free and glycosidically bound forms of the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), showing that it is highly and selectively enriched in red meat. The bound form of Neu5Gc is bioavailable, undergoing metabolic incorporation into human tissues, despite being a foreign antigen. Interactions of this antigen with circulating anti-Neu5Gc antibodies could potentially incite inflammation. Indeed, when human-like Neu5Gc-deficient mice were fed bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Such mice are already prone to develop occasional tumors of the liver, an organ that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized against Neu5Gc and fed bioavailable Neu5Gc developed a much higher incidence of hepatocellular carcinomas, with evidence of Neu5Gc accumulation. Taken together, our data provide an unusual mechanistic explanation for the epidemiological association between red meat consumption and carcinoma risk. This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption.

Proceedings of the National Academy of Sciences, 2014

Compelling evidence for naturally occurring immunosurveillance against malignancies informs and j... more Compelling evidence for naturally occurring immunosurveillance against malignancies informs and justifies some current approaches toward cancer immunotherapy. However, some types of immune reactions have also been shown to facilitate tumor progression. For example, our previous studies showed that although experimental tumor growth is enhanced by low levels of circulating antibodies directed against the nonhuman sialic acid N-glycolyl-neuraminic acid (Neu5Gc), which accumulates in human tumors, growth could be inhibited by anti-Neu5Gc antibodies from a different source, in a different model. However, it remains generally unclear whether the immune responses that mediate cancer immunosurveillance vs. those responsible for inflammatory facilitation are qualitatively and/or quantitatively distinct. Here, we address this question using multiple murine tumor growth models in which polyclonal antibodies against tumor antigens, such as Neu5Gc, can alter tumor progression. We found that although growth was stimulated at low antibody doses, it was inhibited by high doses, over a linear and remarkably narrow range, defining an immune response curve (IRC; i.e., inverse hormesis). Moreover, modulation of immune responses against the tumor by altering antibody avidity or by enhancing innate immunity shifted the IRC in the appropriate direction. Thus, the dualistic role of immunosurveillance vs. inflammation in modulating tumor progression can be quantitatively distinguished in multiple model systems, and can occur over a remarkably narrow range. Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer.

The Journal of Immunology, 2013

Clinical evidence for a more active immune response in humans compared with our closest hominid r... more Clinical evidence for a more active immune response in humans compared with our closest hominid relative, the chimpanzee, includes the progression of HIV infection to AIDS, hepatitis B- and C-related inflammation, autoimmunity, and unwanted harmful immune responses to viral gene transfer vectors. Humans have a unique mutation of the enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH), causing loss of expression of the sialic acid Neu5Gc. This mutation, occurring 2 million years ago, likely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind sialic acids. Previous work showed that human T cells proliferate faster than chimpanzee T cells upon equivalent stimulation. In this article, we report that Cmah(-/-) mouse T cells proliferate faster and have greater expression of activation markers than wild-type mouse T cells. Metabolically reintroducing Neu5Gc diminishes the proliferation and activation of both human and murine Cmah(-/-) T cells. Importantly, Cmah(-/-) mice mount greater T cell responses to an adenovirus encoding an adeno-associated virus capsid transgene. Upon lymphocytic choriomeningitis virus infection, Cmah(-/-) mice make more lymphocytic choriomeningitis virus-specific T cells than WT mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases.

Journal of Biological Chemistry, 2012

Background: The active site of O-GlcNAcase (OGA) is larger than needed to process O-GlcNAc from p... more Background: The active site of O-GlcNAcase (OGA) is larger than needed to process O-GlcNAc from proteins. Results: GlcNGc is assimilated to form UDP-GlcNGc and to generate O-GlcNGc, which can be removed by OGA. Conclusion: OGA has a conserved active site that enables processing of O-GlcNGc. Significance: Substrate tolerance of OGA occurs to process metabolic variants of O-GlcNAc. The O-GlcNAc modification involves the attachment of single ␤-O-linked N-acetylglucosamine residues to serine and threonine residues of nucleocytoplasmic proteins. Interestingly, previous biochemical and structural studies have shown that O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from proteins, has an active site pocket that tolerates various N-acyl groups in addition to the N-acetyl group of GlcNAc. The remarkable sequence and structural conservation of residues comprising this pocket suggest functional importance. We hypothesized this pocket enables processing of metabolic variants of O-GlcNAc that could be formed due to inaccuracy within the metabolic machinery of the hexosamine biosynthetic pathway. In the accompanying paper (Bergfeld, A. K., Pearce, O. M., Diaz, S. L., Pham, T., and Varki, A. (2012) J. Biol. Chem. 287,

International Journal of Surgery, 2013

Clinical Orthopaedics and Related Research®, 2010

THA in young patients is challenging regarding restoration and survival because patients are youn... more THA in young patients is challenging regarding restoration and survival because patients are young, active, and tend to have disturbed anatomy. We asked whether a three-dimensional custom cementless stem could restore hip function, decrease osteolysis and wear, and enhance stem survival in young patients. We retrospectively reviewed 212 patients (233 hips) younger than 50 years (mean, 40 years) at a followup of 5 to 16 years (mean, 10 years). The Merle D'Aubigné-Postel and Harris hip scores improved at last followup. No thigh pain was recorded for any of the patients; 187 of the 212 patients (88%) had full activity recovery, 206 had full range of motion, and 151 had a score greater than 80 points for all five categories of the Hip disability and Osteoarthritis Outcome score. Five patients had femoral osteolysis not associated with pain. With revision for any reason as an end point, the survivorship was 87% (range, 77%-97%) at 15 years, and considering stem revision only, the survivorship was 93% (confidence interval, 90%-97%) at 15 years. Our data compare favorably with those from series using standard cementless stems at the same followup with a high percentage of patients achieving functional restoration and a low rate of complications.

Carbohydrate Research, 2010

a b s t r a c t N-Glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid, which may play a s... more a b s t r a c t N-Glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid, which may play a significant role in human pathologies, such as cancer and vascular disease. Further studies into the role of Neu5Gc in human disease are hindered by limited sources of this carbohydrate. Using a chemo-enzymatic approach, Neu5Gc was accessed in six steps from glucose. The synthesis allows access to gram-scale quantities quickly and economically and produces Neu5Gc in superior quality to commercial sources. Finally, we demonstrate that the synthesized Neu5Gc can be incorporated into the cell glycocalyx of human cells, which do not naturally synthesize this sugar. The synthesis produces Neu5Gc suitable for in vitro or in vivo use.

The various systems of public redress allow citizens to seek remedies for what they perceive to b... more The various systems of public redress allow citizens to seek remedies for what they perceive to be poor treatment, mistakes, faults or injustices in their dealings with departments or agencies. They are the arrangements for getting things put right, remedying grievances, securing a second view or appealing a disputed decision and, where compensation is appropriate, the means through which this can be sought.

Cancer research, Jan 16, 2015

The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experim... more The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here we show that IL-6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL-6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared to VEGF-stimulated vessels. The mechanism of IL-6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as Angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL-6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies there was an association between levels of IL-6mRNA, Jagged1 and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL-6 and for understanding abnormal angiogenesis in canc...

OncoImmunology, 2014

We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor pro... more We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor progression, dependent upon the dosage used. The narrow range over which this immune response curve (IRC) occurs is surprising. Here we discuss features of the IRC, the mechanisms identified so far, and the potential clinical implications.

The Journal of biological chemistry, Jan 6, 2015

As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expr... more As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac, was demonstrated. PolySia is known to modulate cell adhesion, migration and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor (BDNF) normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc caused resistance to Neu1 induced polySia turnover, and also inhibited the associated release of BDNF. These results indicate the importance of rapid turnover of the polySia g...

Proceedings of the National Academy of Sciences of the United States of America, Jan 24, 2015

Atlas of the oral and maxillofacial surgery clinics of North America, 2015

The effective and efficient management of a patient with a neck mass in a 1-stop clinic requires ... more The effective and efficient management of a patient with a neck mass in a 1-stop clinic requires a collaborative and harmonious partnership among surgeon, radiologist, and pathologist. In this article, theoretic and practical issues are addressed to optimize patient care when prescribing, planning, performing, and interpreting imaging for neck disease.

Oncoimmunology, 2014

We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor pro... more We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor progression, dependent upon the dosage used. The narrow range over which this immune response curve (IRC) occurs is surprising. Here we discuss features of the IRC, the mechanisms identified so far, and the potential clinical implications.

Proceedings of the National Academy of Sciences of the United States of America, Jan 30, 2014

Certain pathogenic bacteria are known to modulate the innate immune response by decorating themse... more Certain pathogenic bacteria are known to modulate the innate immune response by decorating themselves with sialic acids, which can engage the myelomonocytic lineage inhibitory receptor Siglec-9, thereby evading immunosurveillance. We hypothesized that the well-known up-regulation of sialoglycoconjugates by tumors might similarly modulate interactions with innate immune cells. Supporting this hypothesis, Siglec-9-expressing myelomonocytic cells found in human tumor samples were accompanied by a strong up-regulation of Siglec-9 ligands. Blockade of Siglec-9 enhanced neutrophil activity against tumor cells in vitro. To investigate the function of inhibitory myelomonocytic Siglecs in vivo we studied mouse Siglec-E, the murine functional equivalent of Siglec-9. Siglec-E-deficient mice showed increased in vivo killing of tumor cells, and this effect was reversed by transgenic Siglec-9 expression in myelomonocytic cells. Siglec-E-deficient mice also showed enhanced immunosurveillance of au...

Proceedings of the National Academy of Sciences, 2014

A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term co... more A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term consumption of "red meat" of mammalian origin. Although multiple theories have attempted to explain this human-specific association, none have been conclusively proven. We used an improved method to survey common foods for free and glycosidically bound forms of the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), showing that it is highly and selectively enriched in red meat. The bound form of Neu5Gc is bioavailable, undergoing metabolic incorporation into human tissues, despite being a foreign antigen. Interactions of this antigen with circulating anti-Neu5Gc antibodies could potentially incite inflammation. Indeed, when human-like Neu5Gc-deficient mice were fed bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Such mice are already prone to develop occasional tumors of the liver, an organ that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized against Neu5Gc and fed bioavailable Neu5Gc developed a much higher incidence of hepatocellular carcinomas, with evidence of Neu5Gc accumulation. Taken together, our data provide an unusual mechanistic explanation for the epidemiological association between red meat consumption and carcinoma risk. This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption.

Proceedings of the National Academy of Sciences, 2014

Compelling evidence for naturally occurring immunosurveillance against malignancies informs and j... more Compelling evidence for naturally occurring immunosurveillance against malignancies informs and justifies some current approaches toward cancer immunotherapy. However, some types of immune reactions have also been shown to facilitate tumor progression. For example, our previous studies showed that although experimental tumor growth is enhanced by low levels of circulating antibodies directed against the nonhuman sialic acid N-glycolyl-neuraminic acid (Neu5Gc), which accumulates in human tumors, growth could be inhibited by anti-Neu5Gc antibodies from a different source, in a different model. However, it remains generally unclear whether the immune responses that mediate cancer immunosurveillance vs. those responsible for inflammatory facilitation are qualitatively and/or quantitatively distinct. Here, we address this question using multiple murine tumor growth models in which polyclonal antibodies against tumor antigens, such as Neu5Gc, can alter tumor progression. We found that although growth was stimulated at low antibody doses, it was inhibited by high doses, over a linear and remarkably narrow range, defining an immune response curve (IRC; i.e., inverse hormesis). Moreover, modulation of immune responses against the tumor by altering antibody avidity or by enhancing innate immunity shifted the IRC in the appropriate direction. Thus, the dualistic role of immunosurveillance vs. inflammation in modulating tumor progression can be quantitatively distinguished in multiple model systems, and can occur over a remarkably narrow range. Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer.

The Journal of Immunology, 2013

Clinical evidence for a more active immune response in humans compared with our closest hominid r... more Clinical evidence for a more active immune response in humans compared with our closest hominid relative, the chimpanzee, includes the progression of HIV infection to AIDS, hepatitis B- and C-related inflammation, autoimmunity, and unwanted harmful immune responses to viral gene transfer vectors. Humans have a unique mutation of the enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH), causing loss of expression of the sialic acid Neu5Gc. This mutation, occurring 2 million years ago, likely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind sialic acids. Previous work showed that human T cells proliferate faster than chimpanzee T cells upon equivalent stimulation. In this article, we report that Cmah(-/-) mouse T cells proliferate faster and have greater expression of activation markers than wild-type mouse T cells. Metabolically reintroducing Neu5Gc diminishes the proliferation and activation of both human and murine Cmah(-/-) T cells. Importantly, Cmah(-/-) mice mount greater T cell responses to an adenovirus encoding an adeno-associated virus capsid transgene. Upon lymphocytic choriomeningitis virus infection, Cmah(-/-) mice make more lymphocytic choriomeningitis virus-specific T cells than WT mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases.

Journal of Biological Chemistry, 2012

Background: The active site of O-GlcNAcase (OGA) is larger than needed to process O-GlcNAc from p... more Background: The active site of O-GlcNAcase (OGA) is larger than needed to process O-GlcNAc from proteins. Results: GlcNGc is assimilated to form UDP-GlcNGc and to generate O-GlcNGc, which can be removed by OGA. Conclusion: OGA has a conserved active site that enables processing of O-GlcNGc. Significance: Substrate tolerance of OGA occurs to process metabolic variants of O-GlcNAc. The O-GlcNAc modification involves the attachment of single ␤-O-linked N-acetylglucosamine residues to serine and threonine residues of nucleocytoplasmic proteins. Interestingly, previous biochemical and structural studies have shown that O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from proteins, has an active site pocket that tolerates various N-acyl groups in addition to the N-acetyl group of GlcNAc. The remarkable sequence and structural conservation of residues comprising this pocket suggest functional importance. We hypothesized this pocket enables processing of metabolic variants of O-GlcNAc that could be formed due to inaccuracy within the metabolic machinery of the hexosamine biosynthetic pathway. In the accompanying paper (Bergfeld, A. K., Pearce, O. M., Diaz, S. L., Pham, T., and Varki, A. (2012) J. Biol. Chem. 287,

International Journal of Surgery, 2013

Clinical Orthopaedics and Related Research®, 2010

THA in young patients is challenging regarding restoration and survival because patients are youn... more THA in young patients is challenging regarding restoration and survival because patients are young, active, and tend to have disturbed anatomy. We asked whether a three-dimensional custom cementless stem could restore hip function, decrease osteolysis and wear, and enhance stem survival in young patients. We retrospectively reviewed 212 patients (233 hips) younger than 50 years (mean, 40 years) at a followup of 5 to 16 years (mean, 10 years). The Merle D'Aubigné-Postel and Harris hip scores improved at last followup. No thigh pain was recorded for any of the patients; 187 of the 212 patients (88%) had full activity recovery, 206 had full range of motion, and 151 had a score greater than 80 points for all five categories of the Hip disability and Osteoarthritis Outcome score. Five patients had femoral osteolysis not associated with pain. With revision for any reason as an end point, the survivorship was 87% (range, 77%-97%) at 15 years, and considering stem revision only, the survivorship was 93% (confidence interval, 90%-97%) at 15 years. Our data compare favorably with those from series using standard cementless stems at the same followup with a high percentage of patients achieving functional restoration and a low rate of complications.

Carbohydrate Research, 2010

a b s t r a c t N-Glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid, which may play a s... more a b s t r a c t N-Glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid, which may play a significant role in human pathologies, such as cancer and vascular disease. Further studies into the role of Neu5Gc in human disease are hindered by limited sources of this carbohydrate. Using a chemo-enzymatic approach, Neu5Gc was accessed in six steps from glucose. The synthesis allows access to gram-scale quantities quickly and economically and produces Neu5Gc in superior quality to commercial sources. Finally, we demonstrate that the synthesized Neu5Gc can be incorporated into the cell glycocalyx of human cells, which do not naturally synthesize this sugar. The synthesis produces Neu5Gc suitable for in vitro or in vivo use.