Sangeeta Khare M.S., Ph.D.

Research Microbiologist — Division of Microbiology

Sangeeta Khare, M.S., Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov

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Background

Dr. Sangeeta Khare joined FDA’s National Center for Toxicological Research (NCTR) as a research microbiologist in the Division of Microbiology in 2010. She earned a bachelor’s degree and master’s degree from Kanpur University, India, in life sciences with an emphasis on microbiology and immunology. She obtained a Ph.D. from the All India Institute of Medical Sciences in New Delhi, India in immunomodulation as an alternative for the treatment of infectious disease.

Dr. Khare was awarded a College of Medicine postdoctoral fellowship from the University of Saskatchewan in Saskatoon, Canada, to work on the relationship between dose of antigen and bias for Th1 versus Th2 immune response. She then moved to the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University (as a research scientist and assistant professor) where she conducted research on the host-pathogen interaction with emphasis on the receptor-ligand interaction, enteric pathogens, and gut mucosal immunity. Dr. Khare has extensive experience working in bio safety level (BSL)-3 and animal-BSL-3-level laboratories. She established a special topic course at Texas A&M University to teach various compliance issues of “Laboratory Biosafety and Biosecurity” (BSL-2 and BSL-3) to undergraduate and graduate students. Dr. Khare is also an adjunct faculty at Texas A&M University.

Honors and Awards

2019 NCTR/FDA Special Act Award for outstanding contributions that impact the National Toxicology Program (NTP)/ National Institute of Environmental Health Sciences (NIEHS)/NCTR research initiatives
2019 Indo-US Professorship by the American Society for Microbiology and the Indo-US Science and Technology Forum
Outstanding Service Award—Microbiome and Host Cell Interaction Study Team, FDA/NCTR
FDA/NCTR Diversity Award
FDA/NCTR Special Act Award
Research Fellowship from the Council of Scientific and Industrial Research (CSIR)
International Travel Award from CSIR
Travel award from James W. McLaughlin Fund
Travel award from Burroughs Wellcome Fund
Best Paper Presentation awards from various scientific organizations

Dr. Khare represents NCTR and FDA in various scientific working groups including:

Immunotoxicology Working Group Committee
Nanotechnology Standard Sub-Committee
FDA Foods Program: Omics Technical Advisory Group
Microbiome Working Group
NIH-FDA Joint Agency Microbiome Group

She is an expert reviewer for several journals and served as grant reviewer for the Biomedical Advanced Research and Development Authority FDA, U.S. Department of Agriculture, the NIEHS, and several other international grant organizations. Dr. Khare has organized multiple workshops and conferences and has supervised several undergraduate, graduate, and postdoctoral scientists. She served as an FDA commissioner fellow preceptor in 2013 and an interagency FDA mentor in 2019. She has been invited to share her research findings at other FDA centers, national and international conferences, as well as medical institutes and universities within the United States and abroad. These interactions have led to active collaborations with scientists from other federal agencies (NIEHS) and FDA Product Centers (Center for Veterinary Medicine, Center for Food Safety and Applied Nutrition, and Center for Drug Evaluation and Research) and FDA’s Office of Regulatory Affairs. She has also collaborated with scientists from academia including Harvard University, University of Connecticut, University of Arkansas for Medical Sciences, University of Arkansas at Little Rock, and Texas A&M University.

Research Interests

Dr. Khare works on cutting-edge xenobiotic-microbiome-host communication, host-pathogen interaction, and nanoparticle research. She has successfully used in vivo, ex vivo, and in vitro models for microbiome assessment during the interaction of xenobiotics to disclose science-based evidence for regulatory sciences. She applies advanced technologies that could be used as endpoints to evaluate the safety of xenobiotics in the gastrointestinal tract. For example, under an interagency agreement with NTP/NIEHS and FDA, her research team is performing risk assessments of several xenobiotic compounds (Aloin, Arsenic, Silver nanoparticle, BisphenolAF, Triclosan) using non-animal and animal models to delineate the impact on the intestinal microbiome and gut-associated immune response during exposure to acute/chronic/repeated exposure of xenobiotics. Moreover, recent efforts focus on the development of models that reveal translation from animal to human. The outcome of this research is in line with the FDA Strategic Policy Roadmap to “empower consumers to make better and more informed decisions about their diets and health.”

Another aspect of Dr. Khare’s research is to assess the impact of emerging nanomaterial on the gastrointestinal tract. Under a Broad Agency Announcement between the Arkansas Research Consortium in Nanotoxicity and the FDA, Dr. Khare led a project to perform safety assessments of carbon-based nanomaterial (Graphene and Carbon Nano Tubes). Dr. Khare’s laboratory has provided data that can be used as additional endpoints in the safety evaluation of nanotechnology-derived products which supplements the traditional metabolism, toxicity, and tissue-residue disposition information used in toxicology risk assessments.

The use of veterinary antimicrobial drugs in food-producing animals may result in antimicrobial-drug residues in or on the edible products derived from treated animals. There are ongoing concerns that the residual amount of antibiotic may cause emergence of antimicrobial resistance in intestinal-microbial populations, as well as lead to the development of cross-resistance for other classes of antibiotics. In collaboration with FDA’s Center for Veterinary Medicine, studies are in progress to evaluate the effects of residual amounts of antibiotics on the development of antibiotic resistance and gastrointestinal permeability. Dr. Khare’s laboratory uses in vitro and ex vivo models to address this emerging FDA concern and highlights the importance of evaluating toxicity of residual concentrations of antimicrobial agents in food. Data from these studies may aid in establishing guidance for human food-safety assessments.

Scientists from academia and other government agencies have reached out to Dr. Khare for collaborations. For example, she is a collaborator on a study conducted at the University of Arkansas for Medical Sciences to address links between environment pollutant exposure, obesity, and the microbiome. She has also collaborated with investigators from Harvard University to analyze the impact of edible nanomaterial on the intestinal microbiota. In collaboration with other scientists at NCTR her research group is making efforts to identify the link of intestinal microbiome with extraintestinal diseases using transgenic animals and collaborative cross animals. The outcomes of collaborative projects within NCTR and with FDA Product Centers, the NTP, and academic institutions are in line with the FDA’s Strategic Plan on Regulatory Science to “Evaluate Innovative Emerging Technologies” and “Modernize Toxicology to Enhance Product Safety.” The long-term goal of Dr. Khare’s research is to advance regulatory science by understanding the complex relationship of the gastrointestinal tract with commensal bacteria, invading enteric pathogens and residues (antibiotics, drugs, pesticides, herbicides, and additives) in consumed food products. The outcome of this research will provide a comprehensive understanding of the mechanistic interaction of xenobiotics-host-microbiome. These findings will form a basis to draft a decision tree for gastrointestinal risk assessment.

Professional Societies/National and International Groups

American Society of Microbiology
Member
2002 – Present

Poster Presentation Judge
2020

FDA and Arkansas Graphene Consortium
Member
2014 – 2016

FDA-NIH-NIST-USDA Joint Agency Microbiome Committee
Biannual/Annual Conference Organizer/Speaker
2018, 2019, 2021

Quarterly Webinar, FDA-NIH-NIST-USDA Joint Agency Microbiome Committee
Organizer
2019 – Present

Global Summit on Regulatory Science
Panel Member
2016

Health and Environmental Sciences Institute
Member, Microbiome Subcommittee
2017 – 2019

Indian Immunology Society
Life Member
1995 – Present

International Society of Infectious Diseases
Member
2010 – Present

Johne’s Disease Integrated Program
Member/Grant Reviewer
2005 – 2018

Mid-South Computational Biology and Bioinformatics Society
Member
2015 – 2018

Society of Toxicology Continuing Education Session
Member/Speaker
2022

Member/Co-Chair/Speaker
2019

Selected Publications

Impact of Chronic Tetracycline Exposure on Human Intestinal Microbiota in a Continuous Flow Bioreactor Model.
Ahn Y., Jung J.Y., Kweon O., Veach B.T., Khare S., Gokulan K., Piñeiro S.A., and Cerniglia C.E.
Antibiotics. 2021, 10, 886. https: / / doi.org/10.3390 / antibiotics10080886.

Co-Exposure to Boscalid and TiO2 (E171) or SiO2 (E551) Downregulates Cell Junction Gene Expression in Small Intestinal Epithelium Cellular Model and Increases Pesticide Translocation.
Cao X., Khare S., DeLoid G.M., Gokulan K., and Demokritou P.
NanoImpact. 2021, DOI: 10.1016/j.impact.2021.100306.

Conformational Changes of the Receptor Binding Domain of SARS-CoV-2 Spike Protein and Prediction of a B-cell Antigenic Epitope Using Structural Data.
Khare S., Azevedo M., Parajuli P., and Gokulan K.
Front. Artif. Intell. 2021, doi: 10.3389/frai.2021.630955.

Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability.
Gokulan K., Williams K., Orr S.E., and Khare S.
Int. J. Mol. Sci. 2021, 22(1), 9; https://doi.org/10.3390/ijms22010009.

Differential Toxicological Outcome of Corn Oil Exposure in Rats and Mice as Assessed by Microbial Composition, Epithelial Permeability and Ileal Mucosa-Associated Immune Status.
Gokulan K., Kumar A., Lahiani H., Sutherland V., Cerniglia C.E., and Khare S.
Toxicological Sciences. 2021, 180 (1): 89–102; doi: 10.1093/toxsci/kfaa177.

Sex-Dependent Effects on Liver Inflammation and Gut Microbial Dysbiosis After Continuous Developmental Exposure to Trichloroethylene in Autoimmune-Prone Mice.
Blossom S.J., Gokulan K., Arnold M.G., and Khare S.
Frontiers in Pharmacology. 2020, 11:569008; doi: 10.3389/fphar.2020.569008.

The Gut Microbiome and Xenobiotics: Identifying Knowledge Gaps.
Sutherland V.L., McQueen C.A., Mendrick D., Gulezian D., Cerniglia C., Foley S., Forry S., Khare S., Liang X., Manautou J.E., Tweedie D., Young H., Alekseyenko A.V., Burns F., Dietert R., and Wilson A.
Toxicol Sci. 2020, 176(1):1-10. doi: 10.1093/toxsci/kfaa060.

Assessment of Silver Release and Biocidal Capacity from Silver Nanocomposite Food Packaging Materials.
Trbojevicha R.A., Khare S., Limc J.H., Watanabed F., Gokulan K., Krohmaly K., and Williams K.M.
Food and Chemical Toxicology. 2020, 145:111728; doi: 10.1016/j.fct.2020.111728.

Effects of Ingested Nanocellulose on Intestinal Microbiota and Homeostasis in Wistar Han Rats.
Khare S., DeLoid G.M., Molina R.M., Gokulan K., Couvillion S.P., Bloodsworth K.J., Eder E.K., Wong A.R., Hoyt D.W., Bramer L.M., Thomas Metz T.O., Thrall B.D., Brain J.D., and Demokritou P.
NanoImpact. 2020, 18: 100216; doi: 10.1016/j.impact.2020.100216.

Effects of Acute and Chronic Exposure to Residual Level Erythromycin on Human Intestinal Epithelium Cell Permeability and Cytotoxicity.
Hao H., Gokulan K., Piñeiro S.A., Williams K.M., Yuan Z., Cerniglia C.E., and Khare S.
Microorganisms. 2019, 6;7(9). pii: E325. doi: 10.3390/microorganisms7090325.

The Impact of Pristine Graphene on Intestinal Microbiota Assessed Using a Bioreactor-Rotary Cell Culture System.
Lahiani M., Gokulan K., Williams K., and Khare S.
ACS Appl Mater Interfaces. 2019, 11(29):25708-25719; doi: 10.1021/acsami.9b07635.

A Single or Short Time Repeated Arsenic Oral Exposure in Mice Impacts mRNA Expression for Signaling and Immunity Related Genes in the Gut.
Arnold M.G., Gokulan K., Doerge D.R., Vanlandingham M., Cerniglia C.E., and Khare S.
Food Chem Toxicol. 2019, 132:110597. doi: 10.1016/j.fct.2019.110597.

Alteration in the mRNA Expression of Genes Associated with Gastrointestinal Permeability and Ileal TNF-α Secretion Due to the Exposure of Silver Nanoparticles in Sprague-Dawley Rats.
Orr S.E., Gokulan K., Boudreau M., Cerniglia C.E., and Khare S.
J Nanobiotechnology. 2019, 13;17(1):63. doi: 10.1186/s12951-019-0499-6.

Aloin Alters the Intestinal Bacterial Community Structure and Short Chain Fatty Acids Metabolism.
Gokulan K., Kolluru P., Cerniglia C.E., and Khare S.
Front. Microbiol. 2019, 10:474; doi: 10.3389/fmicb.2019.00474.

In Vitro Test Systems to Determine Tetracycline Residue Binding to Human Feces.
Ahn Y., Jung J.Y., Veach B.T., Khare S., Gokulan K., Piñeiro S.A., and Cerniglia C.E.
Regul Toxicol Pharmacol. 2018, 99:105-115; doi: 10.1016/j.yrtph.2018.09.013.

Structure and Inhibitor Specificity of L,D-Transpeptidase (LdtMt2) from Mycobacterium tuberculosis and Antibiotic Resistance: Calcium Binding Promotes Dimer Formation.
Gokulan K., Khare S., Cerniglia C.E., Foley S.L., and Varughese K.I.
AAPS J. 2018, 20(2):44. doi: 10.1208/s12248-018-0193-x.

Irreversible Effects of Trichloroethylene on the Gut Microbial Community and Gut-Associated Immune Responses in Autoimmune-Prone Mice.
Khare S., Gokulan K., Williams K., Bai S., Gilbert K.M., and Blossom S.J.
J Appl Toxicol. 2018, 39(2):209-220; doi: 10.1002/jat.3708.

Exposure to Arsenite in CD-1 Mice During Gestational to Adult Developmental Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Response.
Gokulan K., Arnold M., Jensen J., Vanlandingham M., Twaddle N.C., Doerge D.R., Cerniglia C.E., and Khare S.
MBio. 2018, 9(4):e01418-18; doi: 10.1128/mBio.01418-18.

Responses of Intestinal Virome to Silver Nanoparticles: Safety Assessment by Classical Virology, Whole Genome Sequencing and Bioinformatics Approaches.
Gokulan K.†, Bekele A.Z.†, Drake K.L., and Khare S. † Contributed equally
International Journal of Nanomedicine. 2018, 13:2857-2867; doi: 10.2147/IJN.S161379.

Opposing Actions of Developmental Trichloroethylene and High-Fat-Diet Co-Exposure on Markers of Lipogenesis and Inflammation in Autoimmune-Prone Mice.
Blossom S.J., Fernandes L., Bai S., Khare S., Gokulan K., Yuan Y., DeWall M., Simmen F.A., and Gilbert K.M.
Toxicol Sci. 2018, 164(1):313-327. doi: 10.1093/toxsci/kfy091.

Lab Members

Contact information for all lab members:
(870) 543-7121
NCTRResearch@fda.hhs.gov

Amit Kumar, MS
ORISE Fellow

Mohamed Lahiani, Ph.D.
Postdoctoral Fellow

Contact Information: Sangeeta Khare; (870) 543-7121

Expertise: Expertise

Approach

Domain

Technology & Discipline

Toxicology