Fai Poon - Academia.edu (original) (raw)

Papers by Fai Poon

Biomedical and Pharmacology Journal, Jun 30, 2023

This chapter discusses the molecular basis of learning and memory, specifically the Hebbian theor... more This chapter discusses the molecular basis of learning and memory, specifically the Hebbian theory, which suggests that coincident activation of pre- and postsynaptic neurons leads to modifications in synaptic efficacy, creating associative links between the neurons. Memories are stored as alterations of these synaptic changes. The chapter will also discuss three basic assumptions regarding the neurochemical basis of learning and memory, including the requirement for protein synthesis for long-term memory formation, and the storage of memory in synaptic connections. The passage also discusses long-term potentiation (LTP) as the most frequently studied cellular basis of learning and memory in vertebrates, including its properties such as state-dependence, input specificity, and associativity. LTP is considered an analog of memory since it is a long-lasting alteration in neuronal function that results from a brief period of stimulus.

Biomedical and Pharmacology Journal, Jun 15, 2019

Biomedical and Pharmacology Journal, Jun 13, 2018

Their ease of growth and transfection makes HEK293 cells a common cell culture in academic resear... more Their ease of growth and transfection makes HEK293 cells a common cell culture in academic research. In addition, high transfection efficiency of HEK293 cells enable production of exogenous proteins or viruses for pharmaceutical and biomedical research purposes. Recently, HEK293 cells has gained attention due to it is versatility for transfection experiments, particularly the propagation of adenoviral-based and retroviral-based vectors during CART-T bioprocess. Since traceability is critical to pharmaceutical manufacturing process, we provide a mini review to clarify the historical development and intent use of different variants of HEK293 cells. This review should provide a key reference for the HEK293 variants' historical and developmental background.

SunText review of biotechnology, 2020

Biomedical and Pharmacology Journal, Dec 25, 2017

Successful therapeutic commercialization requires the demonstration of efficacy and safety of a d... more Successful therapeutic commercialization requires the demonstration of efficacy and safety of a drug during clinical trials, as well as the commercial feasibility of drug production with consistent quality. Mitigating risk in these three areas is the key strategy for pharmaceutical development success. One of the most effective ways of risk mitigation during therapeutic development is to perform drugability assessments of the molecule. Drugability assessment studies facilitate our understanding of biotherapeutics, predict clinical outcomes, and provide rationales for molecular optimization. Better understanding of biotherapeutic drugability ensures the manufacturability, safety, and efficacy in clinical development. Therefore, drugability assessment is the key for successful biotherapeutic commercialization. Here, we reviewed current literature, and summarized the major durability studies of biotherapeutics.

Lambert Academic Publishing eBooks, 2009

Bioequivalence & bioavailability international journal, 2018

The commercial success and expiring patents of biological therapeutics has made biosimilars becom... more The commercial success and expiring patents of biological therapeutics has made biosimilars become attractive to pharmaceutical companies. However, the cost of manufacturing biosimilars has remained a challenge for many companies. Therefore, the ability to mimic the biologically active molecule at the lowest possible cost via cell culture has become the key of successful biosimilar development. Hence, we review current cell culture technologies that are relevant to biosimilar development. The cell line, culture media and bioprocess technology platforms discussed in current review lays a good scientific foundation for the technological competitiveness of biosimilar companies.

who provides helpful guidance and encouragement during his doctoral research from its beginnings ... more who provides helpful guidance and encouragement during his doctoral research from its beginnings to its completion. The author is also deeply indebted his dissertation committee members for their supports. The author would also like to express his appreciation to his collaborators and members of Professor Butterfield's research group for creating the intellectual community that makes scholarly work a pleasurable and enlivening the social life during his doctoral research. The author is thankful for the endless support and encouragements of the author's parents and his sister, and he will never forgive himself for not being able to taking care of his family. The author would also like to thank three people especially. His grandmother, her suffer of dementia have initiated the author's interest in age-related dementia. His grandfather, his death during author's doctoral study helped him to understand life is more than science. His wife, her endless love, support and patience make him a better person.

Chinese Journal of Chemical Engineering, May 1, 2019

identification of canonical metabolites linking critical process parameters to monoclonal antibod... more identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development. Cjche (2018),

Tissue & Cell, Jun 1, 2019

The increasingly competitive biopharmaceutical industry requires companies to focus on rapid and ... more The increasingly competitive biopharmaceutical industry requires companies to focus on rapid and low-cost cell line development. Single-cell cloning (SCC) is a critical and high-value process for cell line development, and typically problematic because single cell proliferates slowly when cultivated at low cell densities. Conditioned media (CM) provide autocrine growth factors to facilitate single cell proliferation, thus improve SCC efficiency. However, conditioned media (CM) are not a feasible solution for industrial cell line development due to variation and cross-contamination concerns. Here, we have found an improvement in the SCC efficiency similar to CM when soy hydrolysate was supplemented in SCC media. Therefore, we concluded that hydrolysate can mimic the autocrine growth factor(s) effect to improve cloning efficiency observed in CM.

Springer eBooks, Dec 25, 2007

World Journal of Microbiology & Biotechnology, May 1, 2015

Sialic acid levels of therapeutic glycoprotein play an important role in plasma half-life. An und... more Sialic acid levels of therapeutic glycoprotein play an important role in plasma half-life. An undesirable decrease of sialic acid content was observed when we increased Fc-fusion protein productivity fourfold in a GS-CHO cell line by bioprocess optimization. We investigated the potential mechanism for the sialic acid content reduction. We found that limited nucleotide sugar precursor and the extracellular sialidase were not responsible for the reduction of the sialic acid content after titer improvement. Oligosaccharide analysis revealed that the lack of protein galactosylation was the potential cause for the reduction of sialic acid content. Thus we validated this notion by evaluated galactose supplementation in 2 L bioreactors. Cell culture performance was not impacted by addition of up to 40 mM galactose except for the glucose consumption rate. Addition of 20 mM galactose to the bioreactor resulted in the increase of 44 % for total sialic acid content and 20.3 % for sialylated glycans. These data were further validated when the process was run on 200 L scaled bioreactor. These data together show that the galactosylation plays an apparent role in sialylation in our current system.

Clinics in Geriatric Medicine, May 1, 2004

Aging, defined as the gradual alteration in structure and function that occurs over time, eventua... more Aging, defined as the gradual alteration in structure and function that occurs over time, eventually leads to increased probability of nondisease-or nontrauma-related death [1]. Aging is associated with the impairment of physiological systems such as the central nervous system (CNS), homeostatic system, immune system, and others. Functional impairments of the CNS is associated with increased susceptibility to develop many neurodegenerative diseases such as Alzheimer's diseases (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Several theories have been offered to understand the phenomenon of aging through: (1) explaining how the loss of homeostasis occurs in individual organisms during the latter part of life, (2) accounting for the lifespan variation among cohort genetic strains and species, (3) identifying the crucial factors responsible for lifespan extension by genetic mutation or experimental regimens such as caloric restriction (CR), and (4) demonstrating that variation of senescent factors can manipulate the rate of aging [2]. A credible theory of aging should address these criteria. In the past 3 decades, Harman's free radical theory [3] has gained relatively strong support in this area. The free radical theory of aging postulates that the free radical reactions with biomolecules, such as proteins and lipid membranes, are responsible for the

Neurobiology of Disease, May 1, 2006

Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cog... more Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cognitive function and early dementia or clinically probable Alzheimer's disease (AD). Oxidative stress plays a significant role in AD and is increased in the superior/ middle temporal gyri of MCI subjects. Because AD involves hippocampal-resident memory dysfunction, we determined protein oxidation and identified the oxidized proteins in the hippocampi of MCI subjects. We found that protein oxidation is significantly increased in the hippocampi of MCI subjects when compared to age-and sex-matched controls. By using redox proteomics, we determined the oxidatively modified proteins in MCI hippocampus to be A-enolase (ENO1), glutamine synthetase (GLUL), pyruvate kinase M2 (PKM2) and peptidyl-prolyl cis/trans isomerase 1 (PIN1). The interacteome of these proteins revealed that these proteins functionally interact with SRC, hypoxia-inducible factor 1, plasminogen (PLG), MYC, tissue plasminogen activator (PLAT) and BCL2L1. Moreover, the interacteome indicates the functional involvement of energy metabolism, synaptic plasticity and mitogenesis/proliferation. Therefore, oxidative inactivation of ENO1, GLUL and PIN1 may alter these cellular processes and lead to the development of AD from MCI. We conclude that protein oxidation plays a significant role in the development of AD from MCI and that the oxidative inactivation of ENO1, GLUL, PKM2 and PIN1 is involved in the progression of AD from MCI. The current study provides a framework for future studies on the development of AD from MCI relevant to oxidative stress.

Oxidative stress and disease, Nov 21, 2005

Neuroscience, 2005

Protein oxidation has been shown to lead to loss of protein function, increased protein aggregati... more Protein oxidation has been shown to lead to loss of protein function, increased protein aggregation, decreased protein turnover, decreased membrane fluidity, altered cellular redox poteintial, loss of Ca 2+ homeostaisis, and cell death. There is increasing evidence that protein oxidation is involved in the pathogenesis of Alzheimer's disease and amyloid beta-peptide (1-42) has been implicated as a mediator of oxidative stress in AD. However, the specific implications of the oxidation induced by A␤(1-42) on the neurodegeneration evident in AD are unknown. In this study, we used proteomic techniques to identify specific targets of oxidation in transgenic Caenorhabditis elegans (C. elegans) expressing human A␤(1-42). We identified 16 oxidized proteins involved in energy metabolism, proteasome function, and scavenging of oxidants that are more oxidized compared to control lines. These results are discussed with reference to Alzheimer's disease.

Biotechnology Letters, Mar 18, 2015

Objective To develop a rapid process analytical technology (PAT) tool that can measure sialic aci... more Objective To develop a rapid process analytical technology (PAT) tool that can measure sialic acid content of an Fc-fusion protein from cell culture samples. Results A statistical significant correlation between the sialic acid content and size-exclusion chromatography (SEC)-HPLC retention time of an Fc-fusion protein was observed when analyzing the titer of the samples. Using linear fitting analysis, the data fit the model well with R 2 = 0.985. Based on the SDS-PAGE and oligosaccharide analysis, we speculate that the amounts of the glycans could expand the structure of the Fc-fusion protein. This was manifested by the SEC-HPLC method in which proteins were separated based on its molecular size. In order to development a robust PAT method, an internal standard was used to improve the precision of the method by reducing systematic errors. We found the change of SEC retention time (delta t) and sialic acid content were highly correlated (R 2 = 0.992). This method was further validated by a 1500 l production process. Conclusion SEC-HPLC is a promising PAT tool to monitor the sialic acid content of Fc-fusion protein during biomanufacturing or medium optimization processes. Keywords Cell culture Á Critical quality attributes Á Critical quality parameters Á Fc-fusion protein Á Glycosylation Á Process analytical technology Á SEC-HPLC Á Sialic acid

Journal of Bioscience and Bioengineering, Dec 1, 2015

Basal medium design is considered one of the most important steps in process development. To opti... more Basal medium design is considered one of the most important steps in process development. To optimize chemically defined (CD) media efficiently and effectively for the biopharmaceutical industry, a two-step rational strategy was applied to optimize four antibody producing Chinese hamster ovary (CHO) cell lines. In the first step, 48 of 52 components of our in-house medium were divided into three groups according to their characteristics. In the next step, these groups were optimized by spent medium analysis, response surface methodology and mixture design. Because these steps in our strategy involved dividing medium components into groups and subsequently adjusting the concentration of the components, we termed this medium development strategy "divide and conquer". By applying the strategy, we were able to improve the titers of CHO-S, CHO-DG44 and two CHO-K1 cell lines 1.92, 1.86, 2.92 and 1.62-fold, respectively, in 8 weeks with fewer than 60 tests. This divide-and-conquer strategy was efficient, effective, scalable and universal in our current study and offered a new approach to CD media development.

Amyotrophic lateral sclerosis (ALS) is an age-related, fatal motor neuron degenerative disease oc... more Amyotrophic lateral sclerosis (ALS) is an age-related, fatal motor neuron degenerative disease occurring both sporadically (sALS) and heritably (fALS), with inherited cases accounting for approximately 10% of diagnoses. Although multiple mechanisms likely contribute to the pathogenesis of motor neuron injury in ALS, recent advances suggest that oxidative stress may play a significant role in the amplification, and possibly the initiation,

International Journal of Developmental Neuroscience, 2006

Objectives: Neurotrophic factors play key roles in the developing auditory pathway including the ... more Objectives: Neurotrophic factors play key roles in the developing auditory pathway including the sensory epithelium of the inner ear, and structures involved in the central nervous processing of auditory stimuli. In the present investigation, we explored a possible implication of variant BDNF in the susceptibility to chronic tinnitus. Methods: 222 subjects complaining of chronic tinnitus were recruited from a tinnitus clinic and underwent detailed neurootological examinations including otoscopy, stapedius reflexes, middle ear pressure measurements, pure tone audiometry, tinnitus pitch and loudness matches. Subjects were genotyped for a biallelic BDNF missense variant (Val66Met). Prevalence of the substitution was compared to the prevalence in an ethnically homogenous group of healthy controls (N = 317). Results: Carriers of the Met variant were significantly less likely to develop chronic tinnitus with comorbid hearing impairment (p = .02, OR = 1.62, 95% CI = 1.1-2.5). When no assumptions of dominance were made for the minor allele, the Met allele still conferred protection against tinnitus with hearing impairment (p = .05, OR = 1.42, 95% CI = 1.0-2.0). Conclusions: The present study suggests a role of variant BDNF in modulating the genetic susceptibility to chronic tinnitus with hearing impairment. Possible implications of this finding include a differential response to the pharmacological treatment of tinnitus, and specifically, to the neurotrophic effects of antidepressants.

Biomedical and Pharmacology Journal, Jun 30, 2023

This chapter discusses the molecular basis of learning and memory, specifically the Hebbian theor... more This chapter discusses the molecular basis of learning and memory, specifically the Hebbian theory, which suggests that coincident activation of pre- and postsynaptic neurons leads to modifications in synaptic efficacy, creating associative links between the neurons. Memories are stored as alterations of these synaptic changes. The chapter will also discuss three basic assumptions regarding the neurochemical basis of learning and memory, including the requirement for protein synthesis for long-term memory formation, and the storage of memory in synaptic connections. The passage also discusses long-term potentiation (LTP) as the most frequently studied cellular basis of learning and memory in vertebrates, including its properties such as state-dependence, input specificity, and associativity. LTP is considered an analog of memory since it is a long-lasting alteration in neuronal function that results from a brief period of stimulus.

Biomedical and Pharmacology Journal, Jun 15, 2019

Biomedical and Pharmacology Journal, Jun 13, 2018

Their ease of growth and transfection makes HEK293 cells a common cell culture in academic resear... more Their ease of growth and transfection makes HEK293 cells a common cell culture in academic research. In addition, high transfection efficiency of HEK293 cells enable production of exogenous proteins or viruses for pharmaceutical and biomedical research purposes. Recently, HEK293 cells has gained attention due to it is versatility for transfection experiments, particularly the propagation of adenoviral-based and retroviral-based vectors during CART-T bioprocess. Since traceability is critical to pharmaceutical manufacturing process, we provide a mini review to clarify the historical development and intent use of different variants of HEK293 cells. This review should provide a key reference for the HEK293 variants' historical and developmental background.

SunText review of biotechnology, 2020

Biomedical and Pharmacology Journal, Dec 25, 2017

Successful therapeutic commercialization requires the demonstration of efficacy and safety of a d... more Successful therapeutic commercialization requires the demonstration of efficacy and safety of a drug during clinical trials, as well as the commercial feasibility of drug production with consistent quality. Mitigating risk in these three areas is the key strategy for pharmaceutical development success. One of the most effective ways of risk mitigation during therapeutic development is to perform drugability assessments of the molecule. Drugability assessment studies facilitate our understanding of biotherapeutics, predict clinical outcomes, and provide rationales for molecular optimization. Better understanding of biotherapeutic drugability ensures the manufacturability, safety, and efficacy in clinical development. Therefore, drugability assessment is the key for successful biotherapeutic commercialization. Here, we reviewed current literature, and summarized the major durability studies of biotherapeutics.

Lambert Academic Publishing eBooks, 2009

Bioequivalence & bioavailability international journal, 2018

The commercial success and expiring patents of biological therapeutics has made biosimilars becom... more The commercial success and expiring patents of biological therapeutics has made biosimilars become attractive to pharmaceutical companies. However, the cost of manufacturing biosimilars has remained a challenge for many companies. Therefore, the ability to mimic the biologically active molecule at the lowest possible cost via cell culture has become the key of successful biosimilar development. Hence, we review current cell culture technologies that are relevant to biosimilar development. The cell line, culture media and bioprocess technology platforms discussed in current review lays a good scientific foundation for the technological competitiveness of biosimilar companies.

who provides helpful guidance and encouragement during his doctoral research from its beginnings ... more who provides helpful guidance and encouragement during his doctoral research from its beginnings to its completion. The author is also deeply indebted his dissertation committee members for their supports. The author would also like to express his appreciation to his collaborators and members of Professor Butterfield's research group for creating the intellectual community that makes scholarly work a pleasurable and enlivening the social life during his doctoral research. The author is thankful for the endless support and encouragements of the author's parents and his sister, and he will never forgive himself for not being able to taking care of his family. The author would also like to thank three people especially. His grandmother, her suffer of dementia have initiated the author's interest in age-related dementia. His grandfather, his death during author's doctoral study helped him to understand life is more than science. His wife, her endless love, support and patience make him a better person.

Chinese Journal of Chemical Engineering, May 1, 2019

identification of canonical metabolites linking critical process parameters to monoclonal antibod... more identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development. Cjche (2018),

Tissue & Cell, Jun 1, 2019

The increasingly competitive biopharmaceutical industry requires companies to focus on rapid and ... more The increasingly competitive biopharmaceutical industry requires companies to focus on rapid and low-cost cell line development. Single-cell cloning (SCC) is a critical and high-value process for cell line development, and typically problematic because single cell proliferates slowly when cultivated at low cell densities. Conditioned media (CM) provide autocrine growth factors to facilitate single cell proliferation, thus improve SCC efficiency. However, conditioned media (CM) are not a feasible solution for industrial cell line development due to variation and cross-contamination concerns. Here, we have found an improvement in the SCC efficiency similar to CM when soy hydrolysate was supplemented in SCC media. Therefore, we concluded that hydrolysate can mimic the autocrine growth factor(s) effect to improve cloning efficiency observed in CM.

Springer eBooks, Dec 25, 2007

World Journal of Microbiology & Biotechnology, May 1, 2015

Sialic acid levels of therapeutic glycoprotein play an important role in plasma half-life. An und... more Sialic acid levels of therapeutic glycoprotein play an important role in plasma half-life. An undesirable decrease of sialic acid content was observed when we increased Fc-fusion protein productivity fourfold in a GS-CHO cell line by bioprocess optimization. We investigated the potential mechanism for the sialic acid content reduction. We found that limited nucleotide sugar precursor and the extracellular sialidase were not responsible for the reduction of the sialic acid content after titer improvement. Oligosaccharide analysis revealed that the lack of protein galactosylation was the potential cause for the reduction of sialic acid content. Thus we validated this notion by evaluated galactose supplementation in 2 L bioreactors. Cell culture performance was not impacted by addition of up to 40 mM galactose except for the glucose consumption rate. Addition of 20 mM galactose to the bioreactor resulted in the increase of 44 % for total sialic acid content and 20.3 % for sialylated glycans. These data were further validated when the process was run on 200 L scaled bioreactor. These data together show that the galactosylation plays an apparent role in sialylation in our current system.

Clinics in Geriatric Medicine, May 1, 2004

Aging, defined as the gradual alteration in structure and function that occurs over time, eventua... more Aging, defined as the gradual alteration in structure and function that occurs over time, eventually leads to increased probability of nondisease-or nontrauma-related death [1]. Aging is associated with the impairment of physiological systems such as the central nervous system (CNS), homeostatic system, immune system, and others. Functional impairments of the CNS is associated with increased susceptibility to develop many neurodegenerative diseases such as Alzheimer's diseases (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Several theories have been offered to understand the phenomenon of aging through: (1) explaining how the loss of homeostasis occurs in individual organisms during the latter part of life, (2) accounting for the lifespan variation among cohort genetic strains and species, (3) identifying the crucial factors responsible for lifespan extension by genetic mutation or experimental regimens such as caloric restriction (CR), and (4) demonstrating that variation of senescent factors can manipulate the rate of aging [2]. A credible theory of aging should address these criteria. In the past 3 decades, Harman's free radical theory [3] has gained relatively strong support in this area. The free radical theory of aging postulates that the free radical reactions with biomolecules, such as proteins and lipid membranes, are responsible for the

Neurobiology of Disease, May 1, 2006

Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cog... more Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cognitive function and early dementia or clinically probable Alzheimer's disease (AD). Oxidative stress plays a significant role in AD and is increased in the superior/ middle temporal gyri of MCI subjects. Because AD involves hippocampal-resident memory dysfunction, we determined protein oxidation and identified the oxidized proteins in the hippocampi of MCI subjects. We found that protein oxidation is significantly increased in the hippocampi of MCI subjects when compared to age-and sex-matched controls. By using redox proteomics, we determined the oxidatively modified proteins in MCI hippocampus to be A-enolase (ENO1), glutamine synthetase (GLUL), pyruvate kinase M2 (PKM2) and peptidyl-prolyl cis/trans isomerase 1 (PIN1). The interacteome of these proteins revealed that these proteins functionally interact with SRC, hypoxia-inducible factor 1, plasminogen (PLG), MYC, tissue plasminogen activator (PLAT) and BCL2L1. Moreover, the interacteome indicates the functional involvement of energy metabolism, synaptic plasticity and mitogenesis/proliferation. Therefore, oxidative inactivation of ENO1, GLUL and PIN1 may alter these cellular processes and lead to the development of AD from MCI. We conclude that protein oxidation plays a significant role in the development of AD from MCI and that the oxidative inactivation of ENO1, GLUL, PKM2 and PIN1 is involved in the progression of AD from MCI. The current study provides a framework for future studies on the development of AD from MCI relevant to oxidative stress.

Oxidative stress and disease, Nov 21, 2005

Neuroscience, 2005

Protein oxidation has been shown to lead to loss of protein function, increased protein aggregati... more Protein oxidation has been shown to lead to loss of protein function, increased protein aggregation, decreased protein turnover, decreased membrane fluidity, altered cellular redox poteintial, loss of Ca 2+ homeostaisis, and cell death. There is increasing evidence that protein oxidation is involved in the pathogenesis of Alzheimer's disease and amyloid beta-peptide (1-42) has been implicated as a mediator of oxidative stress in AD. However, the specific implications of the oxidation induced by A␤(1-42) on the neurodegeneration evident in AD are unknown. In this study, we used proteomic techniques to identify specific targets of oxidation in transgenic Caenorhabditis elegans (C. elegans) expressing human A␤(1-42). We identified 16 oxidized proteins involved in energy metabolism, proteasome function, and scavenging of oxidants that are more oxidized compared to control lines. These results are discussed with reference to Alzheimer's disease.

Biotechnology Letters, Mar 18, 2015

Objective To develop a rapid process analytical technology (PAT) tool that can measure sialic aci... more Objective To develop a rapid process analytical technology (PAT) tool that can measure sialic acid content of an Fc-fusion protein from cell culture samples. Results A statistical significant correlation between the sialic acid content and size-exclusion chromatography (SEC)-HPLC retention time of an Fc-fusion protein was observed when analyzing the titer of the samples. Using linear fitting analysis, the data fit the model well with R 2 = 0.985. Based on the SDS-PAGE and oligosaccharide analysis, we speculate that the amounts of the glycans could expand the structure of the Fc-fusion protein. This was manifested by the SEC-HPLC method in which proteins were separated based on its molecular size. In order to development a robust PAT method, an internal standard was used to improve the precision of the method by reducing systematic errors. We found the change of SEC retention time (delta t) and sialic acid content were highly correlated (R 2 = 0.992). This method was further validated by a 1500 l production process. Conclusion SEC-HPLC is a promising PAT tool to monitor the sialic acid content of Fc-fusion protein during biomanufacturing or medium optimization processes. Keywords Cell culture Á Critical quality attributes Á Critical quality parameters Á Fc-fusion protein Á Glycosylation Á Process analytical technology Á SEC-HPLC Á Sialic acid

Journal of Bioscience and Bioengineering, Dec 1, 2015

Basal medium design is considered one of the most important steps in process development. To opti... more Basal medium design is considered one of the most important steps in process development. To optimize chemically defined (CD) media efficiently and effectively for the biopharmaceutical industry, a two-step rational strategy was applied to optimize four antibody producing Chinese hamster ovary (CHO) cell lines. In the first step, 48 of 52 components of our in-house medium were divided into three groups according to their characteristics. In the next step, these groups were optimized by spent medium analysis, response surface methodology and mixture design. Because these steps in our strategy involved dividing medium components into groups and subsequently adjusting the concentration of the components, we termed this medium development strategy "divide and conquer". By applying the strategy, we were able to improve the titers of CHO-S, CHO-DG44 and two CHO-K1 cell lines 1.92, 1.86, 2.92 and 1.62-fold, respectively, in 8 weeks with fewer than 60 tests. This divide-and-conquer strategy was efficient, effective, scalable and universal in our current study and offered a new approach to CD media development.

Amyotrophic lateral sclerosis (ALS) is an age-related, fatal motor neuron degenerative disease oc... more Amyotrophic lateral sclerosis (ALS) is an age-related, fatal motor neuron degenerative disease occurring both sporadically (sALS) and heritably (fALS), with inherited cases accounting for approximately 10% of diagnoses. Although multiple mechanisms likely contribute to the pathogenesis of motor neuron injury in ALS, recent advances suggest that oxidative stress may play a significant role in the amplification, and possibly the initiation,

International Journal of Developmental Neuroscience, 2006

Objectives: Neurotrophic factors play key roles in the developing auditory pathway including the ... more Objectives: Neurotrophic factors play key roles in the developing auditory pathway including the sensory epithelium of the inner ear, and structures involved in the central nervous processing of auditory stimuli. In the present investigation, we explored a possible implication of variant BDNF in the susceptibility to chronic tinnitus. Methods: 222 subjects complaining of chronic tinnitus were recruited from a tinnitus clinic and underwent detailed neurootological examinations including otoscopy, stapedius reflexes, middle ear pressure measurements, pure tone audiometry, tinnitus pitch and loudness matches. Subjects were genotyped for a biallelic BDNF missense variant (Val66Met). Prevalence of the substitution was compared to the prevalence in an ethnically homogenous group of healthy controls (N = 317). Results: Carriers of the Met variant were significantly less likely to develop chronic tinnitus with comorbid hearing impairment (p = .02, OR = 1.62, 95% CI = 1.1-2.5). When no assumptions of dominance were made for the minor allele, the Met allele still conferred protection against tinnitus with hearing impairment (p = .05, OR = 1.42, 95% CI = 1.0-2.0). Conclusions: The present study suggests a role of variant BDNF in modulating the genetic susceptibility to chronic tinnitus with hearing impairment. Possible implications of this finding include a differential response to the pharmacological treatment of tinnitus, and specifically, to the neurotrophic effects of antidepressants.