Faizan Rashid | University of Illinois at Urbana-Champaign (original) (raw)

Papers by Faizan Rashid

Health Security, 2019

Dual-use research poses a significant challenge for scientists in the biomedical field and for gl... more Dual-use research poses a significant challenge for scientists in the biomedical field and for global health security in general. As the scientific knowledge and materials required for the development of biological agents become progressively more accessible and inexpensive, there is an increased need to understand and improve the governance of scientific research. Prevention of the misuse of facilities, equipment, agents, and scientific knowledge requires high levels of awareness of the concept of dual-use research, starting with early-career scientists and graduate students. In this study, the attitudes and level of awareness of postgraduate students in Pakistan toward the issues surrounding dual-use research were assessed through a survey containing both quantitative and qualitative questions in 32 universities in 4 provinces, federal area, and Azad Jammu and Kashmir regions of Pakistan; 933 students responded. Most (58.2%) had never heard of dual-use research of concern (DURC), while 18.5% had heard the term but were unsure of its meaning. Irrespective of prior knowledge, a higher percentage of students (68.6%) felt an obligation to report research misuse. Considering the need for DURC training, 94.1% of the respondents agreed that the principal investigator should take the responsibility to train students on DURC at the start of a research project. When experimental results having dual-use potential, 69.1% indicated they would publish with limited protocol, with 43.5% indicating they would publish the limited protocol only if there was a way for scientists to access their data. The survey results revealed limited DURC awareness among researchers across Pakistan. However, the respondents, although not formally educated about DURC, were quite aware of its impact. The information gained in this survey will be valuable in addressing country-specific awareness and training needs.

Environmental Epigenetics

Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in... more Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo. Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers Acta2 and Bcl2l1 increased in expression significantly. Transcription factors, including Nef2l2, Hes1, Ppara, and Ppard, were upregulated, while Smarca2 and Pparg were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a and Kdm4c were upregulated. Our wo...

Abstracts from the 7th International Australasian College for Infection Prevention and Control (ACIPC) conference, 2018

Introduction: The current study was aimed to assess the impact of biosafety trainings on knowledg... more Introduction: The current study was aimed to assess the impact of biosafety trainings on knowledge and attitude of life sciences students towards biosafety in Hazara, Khyber Pakhtunkhwa, Pakistan. Methods: This study was conducted from January, 2018 to April, 2018 at 5 different universities. Data was collected from a total of 256 students in various life sciences departments using a pre-designed questionnaire. The information about attitude and use of standard laboratory practices in laboratory and biosafety awareness was obtained using 40 different survey questions. Results: 210 (82%) of study participants had received one or more biosafety trainings in past from four major organizations currently working on biosafety awareness in Pakistan. The knowledge gaps were observed with respect to biosafety in both untrained and trained students for each of the survey question. A significantly lower percentage of untrained students reported knowledge about proper use of PPE's, primary safety devices, waste disposal methods and emergency responses as compared to trained students. Despite of the fact that the trained students had a better knowledge, the compliance rate to various standard laboratory practices ranged from 46.1%-85.2% among trained students. Conclusion: The survey results showed a better attitude and biosafety awareness among trained students as compared to untrained students. However, the lower compliance rate among trained students for some of the standard laboratory practices could be due to non-availability of most of the standard operating procedures revealed from survey results. Therefore, a strong leadership is required to ensure SOP's compliance, supply of PPE's and refresher training's.

International Journal of Toxicology, 2021

Perfluorooctanoic acid (PFOA) is a widespread contaminant in the environment, that is, implicated... more Perfluorooctanoic acid (PFOA) is a widespread contaminant in
the environment, that is, implicated in several toxicities. The
intestinal wall is first surface of interaction with any toxicant
after exposure through the oral route. Previous studies have
demonstrated: increased intestinal bioaccumulation of
PFOA in different experimental animals, PFOA-induced
changes in DNA methylation of several tissues, and alterations
in expression of tight junction (TJ) genes due to epigenetics
changes. Nevertheless, evidence on the toxicity of
PFOA on intestinal epigenetics and TJ genes is limited.
Thus, the present work investigates PFOA-induced changes
in expression of epigenetic genes of the colon in relation to
TJ genes alterations. CD-1 mice were orally dosed with 4
different concentrations of PFOA (1, 5, 10, or 20 mg/kg/d)
for 10 consecutive days, and its bioaccumulation and
induced changes in the expression of TJ and epigenetic
genes in the colon were investigated. The PFOA was accumulated
in very high concentrations in the colon tissue and
decreased the expression levels of DNA methyltransferase
genes (Dnmt3a and DNMT3b). However, no significant
alterations were observed in expression levels of 10-11
translocation (TET1 and TET2) genes. We also found a
significant reduction in the mRNA expression of TJ
protein-1 (TJP1) at the highest concentration of PFOA.
Furthermore, the mRNA expression levels were significantly
increased for occludin (OCLN) and Claudins
(CLDN2, CLDN3, CLDN8) genes at higher concentrations.
Therefore, our study demonstrates that PFOA initiates
DNA methylation alterations and changes the expression
of genes necessary for preserving the integrity of the colon
barrier.

International Journal of Toxicology, 2022

The animal gut microbiota consist of 100 trillion microbes which drives remarkable metabolic act... more The animal gut microbiota consist of 100 trillion microbes
which drives remarkable metabolic activities in the gut.
The alteration of gut microbiota due to xenobiotic toxicity
can lead to severe health consequences. Due to high levels
of perfluoroalkyl and polyfluoroalkyl substances contamination
in environment, we conducted this study to determine
key changes induced by Perfluorooctane sulfonate
(PFOS) and GenX exposure in the gut microbial
functions and liver metabolism. Six groups (n=3) of male
mice were treated with 5, 10, and 20mg/kg of PFOS and 10,
20, and 100 mg/kg of GenX. Two separate control groups
(n=3) of mice were treated with the vehicle control. 16S
rRNA sequencing and untargeted metabolome analysis
were used to analyze the gut microbiome and liver changes
respectively in exposed mice. PFOS was found to have
more profound impact in mice by inducing amino acid
biosynthesis pathways in small intestine and various
fermentation pathways in colon. Whereas, GenX mainly
induced the biosynthesis pathways of amino acids, purine
and vitamin B12 in small intestine and in colon it induced
vitamin B12 and B1 synthesis pathways. Metabolomics
analysis revealed a total of 491 significantly altered
compounds between treatment groups in liver (p<0.01).
These metabolites are associated with host metabolic
pathways mainly involved in lipid synthesis, steroidogenesis,
and metabolism of amino acids, nitrogen, and bile
acids. In conclusion, PFOS and GenX exposure lead to key
alterations in the gut microbial functions in both small
intestine and colon, as well as significant alterations in liver
metabolome leading to host metabolic disorders.

Environmental Epigenetics, 2022

Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in... more Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo. mRNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers Acta2 and Bcl2l1 increased in expression significantly. Transcription factors including Nef2l2, Hes1, Ppara, and Ppard were upregulated while Smarca2 and Pparg were downregulated. Further, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a, Kdm4c were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications in kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.

Pakistan journal of pharmaceutical sciences, 2020

Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria ... more Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria chamomilla L. and Foeniculum vulgare Mill. were selected for their in vitro and in vivo evaluation of anti-Helicobacter pylori activity. In vitro evaluation was performed by using disk diffusion method and minimum inhibitory concentrations were noted while rat models were selected for in vivo activity against four Helicobacter pylori strains isolated form gastric mucosa. Mentha piperita showed largest zone of inhibition with 9 mm diameter among all other extracts. All the plants showed promising anti-Helicobacter pylori activity against four isolates and a reference strain at concentrations of 125, 250, 500 and 1000 μg/ml in comparison with Amoxicillin 1 μg/ml but least MIC was exhibited by Mentha piperita followed by in vivo testing where it competed Amoxicillin at 1000 mg/kg by achieving 80% eradication of Helicobacter pylori in mucosa of infected rats justified by histological examina...

Toxics

Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, ... more Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is sparse. CD1 mice were dosed with PFOA (1, 5, 10, or 20 mg/kg/day) for 10 days, and its accumulation and induced alterations in the expression of epigenetic and tight junction genes in the small intestine and colon were evaluated using LC–MS and qPCR techniques. PFOA reduced the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) primarily in the small intestine whereas, in the colon, a decrease was observed only at high concentrations. Moreover, ten-eleven translocation genes (Tet2 and Tet3) expression was dysregulated in the small intestine, whereas in the colon Tets remained unaffected. The tight junction genes Claudi...

Toxicology Reports, 2020

Perfluorooctanoic acid (PFOA), a manufactured perfluorochemical is a common surfactant and enviro... more Perfluorooctanoic acid (PFOA), a manufactured perfluorochemical is a common surfactant and environmental pollutant found in various consumer products and water sources. Epidemiological studies have demonstrated its association with kidney dysfunction. However, the mechanisms that trigger kidney dysfunction following PFOA exposure is a gap in the field. The work presented explores the potential epigenetic indicators of kidney disease due to exposure to PFOA. In this study, 30 days old CD-1 mice were exposed to 1, 5, 10, or 20 mg/kg/day of PFOA for 10 days. Following acute oral exposure, epigenetic alterations and expression levels of various markers of fibroblast activation were evaluated in kidney tissues. We noted that PFOA-exposed mice exhibited differential methylation yielding 879 differentially methylated regions compared to vehicle. The mRNA expression revealed significant increase in Dnmt1 with decreased Rasal1 expression at higher levels of PFOA exposure suggestive of Rasal1 hypermethylation (an early indicator of fibroblast activation in kidney). Like Dnmt1, we also observed significant increase in Hdac1, 3 and 4. These are class I & II HDACs which are known to be critically altered in some renal diseases. Further, the mRNA expression levels of TGF-β and α-SMA significantly increased compared to vehicle. The KEGG and Go enrichment pathway analysis of reduced representation bisulfite data also revealed pathways implicated in renal fibrosis. Our study shows clear evidence of epigenetic alterations (DNA methylation and HDAC expression changes) in tissues from mouse kidney following PFOA exposure. Our results also suggest that epigenetic alterations in kidney promote the expression of early markers of fibroblast activation.

Health Security, 2019

Dual-use research poses a significant challenge for scientists in the biomedical field and for gl... more Dual-use research poses a significant challenge for scientists in the biomedical field and for global health security in general. As the scientific knowledge and materials required for the development of biological agents become progressively more accessible and inexpensive, there is an increased need to understand and improve the governance of scientific research. Prevention of the misuse of facilities, equipment, agents, and scientific knowledge requires high levels of awareness of the concept of dual-use research, starting with early-career scientists and graduate students. In this study, the attitudes and level of awareness of postgraduate students in Pakistan toward the issues surrounding dual-use research were assessed through a survey containing both quantitative and qualitative questions in 32 universities in 4 provinces, federal area, and Azad Jammu and Kashmir regions of Pakistan; 933 students responded. Most (58.2%) had never heard of dual-use research of concern (DURC), while 18.5% had heard the term but were unsure of its meaning. Irrespective of prior knowledge, a higher percentage of students (68.6%) felt an obligation to report research misuse. Considering the need for DURC training, 94.1% of the respondents agreed that the principal investigator should take the responsibility to train students on DURC at the start of a research project. When experimental results having dual-use potential, 69.1% indicated they would publish with limited protocol, with 43.5% indicating they would publish the limited protocol only if there was a way for scientists to access their data. The survey results revealed limited DURC awareness among researchers across Pakistan. However, the respondents, although not formally educated about DURC, were quite aware of its impact. The information gained in this survey will be valuable in addressing country-specific awareness and training needs.

Environmental Epigenetics

Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in... more Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo. Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers Acta2 and Bcl2l1 increased in expression significantly. Transcription factors, including Nef2l2, Hes1, Ppara, and Ppard, were upregulated, while Smarca2 and Pparg were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a and Kdm4c were upregulated. Our wo...

Abstracts from the 7th International Australasian College for Infection Prevention and Control (ACIPC) conference, 2018

Introduction: The current study was aimed to assess the impact of biosafety trainings on knowledg... more Introduction: The current study was aimed to assess the impact of biosafety trainings on knowledge and attitude of life sciences students towards biosafety in Hazara, Khyber Pakhtunkhwa, Pakistan. Methods: This study was conducted from January, 2018 to April, 2018 at 5 different universities. Data was collected from a total of 256 students in various life sciences departments using a pre-designed questionnaire. The information about attitude and use of standard laboratory practices in laboratory and biosafety awareness was obtained using 40 different survey questions. Results: 210 (82%) of study participants had received one or more biosafety trainings in past from four major organizations currently working on biosafety awareness in Pakistan. The knowledge gaps were observed with respect to biosafety in both untrained and trained students for each of the survey question. A significantly lower percentage of untrained students reported knowledge about proper use of PPE's, primary safety devices, waste disposal methods and emergency responses as compared to trained students. Despite of the fact that the trained students had a better knowledge, the compliance rate to various standard laboratory practices ranged from 46.1%-85.2% among trained students. Conclusion: The survey results showed a better attitude and biosafety awareness among trained students as compared to untrained students. However, the lower compliance rate among trained students for some of the standard laboratory practices could be due to non-availability of most of the standard operating procedures revealed from survey results. Therefore, a strong leadership is required to ensure SOP's compliance, supply of PPE's and refresher training's.

International Journal of Toxicology, 2021

Perfluorooctanoic acid (PFOA) is a widespread contaminant in the environment, that is, implicated... more Perfluorooctanoic acid (PFOA) is a widespread contaminant in
the environment, that is, implicated in several toxicities. The
intestinal wall is first surface of interaction with any toxicant
after exposure through the oral route. Previous studies have
demonstrated: increased intestinal bioaccumulation of
PFOA in different experimental animals, PFOA-induced
changes in DNA methylation of several tissues, and alterations
in expression of tight junction (TJ) genes due to epigenetics
changes. Nevertheless, evidence on the toxicity of
PFOA on intestinal epigenetics and TJ genes is limited.
Thus, the present work investigates PFOA-induced changes
in expression of epigenetic genes of the colon in relation to
TJ genes alterations. CD-1 mice were orally dosed with 4
different concentrations of PFOA (1, 5, 10, or 20 mg/kg/d)
for 10 consecutive days, and its bioaccumulation and
induced changes in the expression of TJ and epigenetic
genes in the colon were investigated. The PFOA was accumulated
in very high concentrations in the colon tissue and
decreased the expression levels of DNA methyltransferase
genes (Dnmt3a and DNMT3b). However, no significant
alterations were observed in expression levels of 10-11
translocation (TET1 and TET2) genes. We also found a
significant reduction in the mRNA expression of TJ
protein-1 (TJP1) at the highest concentration of PFOA.
Furthermore, the mRNA expression levels were significantly
increased for occludin (OCLN) and Claudins
(CLDN2, CLDN3, CLDN8) genes at higher concentrations.
Therefore, our study demonstrates that PFOA initiates
DNA methylation alterations and changes the expression
of genes necessary for preserving the integrity of the colon
barrier.

International Journal of Toxicology, 2022

The animal gut microbiota consist of 100 trillion microbes which drives remarkable metabolic act... more The animal gut microbiota consist of 100 trillion microbes
which drives remarkable metabolic activities in the gut.
The alteration of gut microbiota due to xenobiotic toxicity
can lead to severe health consequences. Due to high levels
of perfluoroalkyl and polyfluoroalkyl substances contamination
in environment, we conducted this study to determine
key changes induced by Perfluorooctane sulfonate
(PFOS) and GenX exposure in the gut microbial
functions and liver metabolism. Six groups (n=3) of male
mice were treated with 5, 10, and 20mg/kg of PFOS and 10,
20, and 100 mg/kg of GenX. Two separate control groups
(n=3) of mice were treated with the vehicle control. 16S
rRNA sequencing and untargeted metabolome analysis
were used to analyze the gut microbiome and liver changes
respectively in exposed mice. PFOS was found to have
more profound impact in mice by inducing amino acid
biosynthesis pathways in small intestine and various
fermentation pathways in colon. Whereas, GenX mainly
induced the biosynthesis pathways of amino acids, purine
and vitamin B12 in small intestine and in colon it induced
vitamin B12 and B1 synthesis pathways. Metabolomics
analysis revealed a total of 491 significantly altered
compounds between treatment groups in liver (p<0.01).
These metabolites are associated with host metabolic
pathways mainly involved in lipid synthesis, steroidogenesis,
and metabolism of amino acids, nitrogen, and bile
acids. In conclusion, PFOS and GenX exposure lead to key
alterations in the gut microbial functions in both small
intestine and colon, as well as significant alterations in liver
metabolome leading to host metabolic disorders.

Environmental Epigenetics, 2022

Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in... more Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo. mRNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers Acta2 and Bcl2l1 increased in expression significantly. Transcription factors including Nef2l2, Hes1, Ppara, and Ppard were upregulated while Smarca2 and Pparg were downregulated. Further, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a, Kdm4c were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications in kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.

Pakistan journal of pharmaceutical sciences, 2020

Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria ... more Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria chamomilla L. and Foeniculum vulgare Mill. were selected for their in vitro and in vivo evaluation of anti-Helicobacter pylori activity. In vitro evaluation was performed by using disk diffusion method and minimum inhibitory concentrations were noted while rat models were selected for in vivo activity against four Helicobacter pylori strains isolated form gastric mucosa. Mentha piperita showed largest zone of inhibition with 9 mm diameter among all other extracts. All the plants showed promising anti-Helicobacter pylori activity against four isolates and a reference strain at concentrations of 125, 250, 500 and 1000 μg/ml in comparison with Amoxicillin 1 μg/ml but least MIC was exhibited by Mentha piperita followed by in vivo testing where it competed Amoxicillin at 1000 mg/kg by achieving 80% eradication of Helicobacter pylori in mucosa of infected rats justified by histological examina...

Toxics

Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, ... more Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is sparse. CD1 mice were dosed with PFOA (1, 5, 10, or 20 mg/kg/day) for 10 days, and its accumulation and induced alterations in the expression of epigenetic and tight junction genes in the small intestine and colon were evaluated using LC–MS and qPCR techniques. PFOA reduced the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) primarily in the small intestine whereas, in the colon, a decrease was observed only at high concentrations. Moreover, ten-eleven translocation genes (Tet2 and Tet3) expression was dysregulated in the small intestine, whereas in the colon Tets remained unaffected. The tight junction genes Claudi...

Toxicology Reports, 2020

Perfluorooctanoic acid (PFOA), a manufactured perfluorochemical is a common surfactant and enviro... more Perfluorooctanoic acid (PFOA), a manufactured perfluorochemical is a common surfactant and environmental pollutant found in various consumer products and water sources. Epidemiological studies have demonstrated its association with kidney dysfunction. However, the mechanisms that trigger kidney dysfunction following PFOA exposure is a gap in the field. The work presented explores the potential epigenetic indicators of kidney disease due to exposure to PFOA. In this study, 30 days old CD-1 mice were exposed to 1, 5, 10, or 20 mg/kg/day of PFOA for 10 days. Following acute oral exposure, epigenetic alterations and expression levels of various markers of fibroblast activation were evaluated in kidney tissues. We noted that PFOA-exposed mice exhibited differential methylation yielding 879 differentially methylated regions compared to vehicle. The mRNA expression revealed significant increase in Dnmt1 with decreased Rasal1 expression at higher levels of PFOA exposure suggestive of Rasal1 hypermethylation (an early indicator of fibroblast activation in kidney). Like Dnmt1, we also observed significant increase in Hdac1, 3 and 4. These are class I & II HDACs which are known to be critically altered in some renal diseases. Further, the mRNA expression levels of TGF-β and α-SMA significantly increased compared to vehicle. The KEGG and Go enrichment pathway analysis of reduced representation bisulfite data also revealed pathways implicated in renal fibrosis. Our study shows clear evidence of epigenetic alterations (DNA methylation and HDAC expression changes) in tissues from mouse kidney following PFOA exposure. Our results also suggest that epigenetic alterations in kidney promote the expression of early markers of fibroblast activation.