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  1. Science & Research (NCTR)

Kuppan Gokulan Ph.D.

Staff Fellow — Division of Microbiology

Kuppan Gokulan
Kuppan Gokulan, Ph.D.

(870) 543-7391
NCTRResearch@fda.hhs.gov  

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 About  |  Publications 


Background

Dr. Kuppan Gokulan graduated in the field of biochemistry and immunology from the All India Institute of Medical Sciences, New Delhi, India. His graduate research was primarily focused on peptide-based vaccine design against human immunodeficiency virus (HIV) and modulates immune response by linking immunomodulators with peptide antigens. 

Prior to joining the FDA Commissioner’s Fellow Program, Dr. Gokulan was a research scientist at Texas A&M University, in the Department of Biochemistry. Dr. Gokulan has extensive hands-on research experience in protein chemistry, structural biology, and in silico modelling. He has used these approaches to solve macromolecular structures that are potential for drug targets for metabolic diseases. In addition, Dr. Gokulan has used a structural biology approach to identify inhibitors/drugs against bacterial enzymes in drug or multidrug-resistant bacteria by employing in silico information, protein homology modelling, and high-throughput drug screening against drug targets or antibiotic-resistant bacteria. 

Dr. Gokulan is currently working as a staff fellow in the Division of Microbiology at NCTR. In 2010, he joined as an FDA Commissioner’s Fellow at NCTR. After completing the FDA Commissioner’s Fellow Program, he worked as an Oak Ridge Institute for Science and Education (ORISE) visiting scientist at NCTR from 2012 to 2015. Dr. Gokulan has also served as an adjunct faculty member in the Department of Physiology and Biophysics at the University of Arkansas for Medical Sciences (UAMS) since 2011. He has a unique background that consists of both FDA regulatory training and biomedical research. During the FDA Commissioner’s Fellow Program, he acquired extensive training in public policy, FDA rules, epidemiology, clinical trials, management of drug discovery, pharmacokinetics, pharmacodynamics, and toxicology. Dr. Gokulan has participated in and completed the New Reviewer, Investigational New Drug Regulations and Policies, and Lifecycle Approach training courses offered by both FDA’s Center for Biologics Evaluation and Research and Center for Drug Evaluation and Research. He is actively involved in FDA’s priority research areas which are essential for regulatory guidance.

In 2014, Dr. Gokulan received an outstanding service award by NCTR for his research contribution in microbiome and host cell interaction. In 2015, he received a CDER grant to conduct research on “Nonclinical modeling and risk assessment of FDA-regulated drug-nanocrystals.” In addition, he is also co-principal investigator on other NCTR projects that include the “Role of plasmid-encoded factors in Salmonella enterica virulence” and the “Effects of graphene-induced toxicity on the intestinal microbiota and gut-associated immune response using in-vitro model system.” Dr. Gokulan has several collaborative research projects with UAMS, Texas A&M University, and University of Connecticut in the area of structure-based drug discovery and the cytotoxic effect of nanocrystal drugs in the gastrointestinal tract.

Research Interests

Dr.Gokulan’s laboratory has five majors areas of research that include:

  • Food safety and Biosecurity
  • Microbes and Host Interactions
  • Antimicrobial Resistance
  • Microbiome in Health and Disease
  • Development of Nonclinical Modeling the Risk Assessment of Nanocrystal Drugs.

In the food-safety arena Dr. Gokulan has established a virulence and persistence assay to monitor S. enterica Heidelberg-induced toxicity using macrophages and intestinal epithelial cells. He is also involved in identifying unique virulence genes and transmissible plasmids that contribute to antibiotic resistance in foodborne pathogens. Understanding of the involvement of plasmid-encoded genes in antimicrobial resistance, colonization, invasion, and formation of the secretary apparatus will provide an improved knowledge of resistance and molecular mechanism of virulence-associated secretion by the T4SS. The outcome of the study will address several unresolved questions of bacterial pathogenesis and bacterial secretion systems. 

Another major focus of research in Dr. Gokulan’s laboratory is to understand the early host immune response during bacterial invasion, and how the bacterial pathogens alter the host immune-response genes via signaling pathways to establish bacterial colonization within the host. He is addressing what factors lead to persistent bacterial infection, even when the host mounts an immune response against the bacterial insult, and how pathogenic microbes evade the immune response. Gokulan's lab is also evaluating the effect of aloin (anthraquinone glycoside) on intestinal bacterial community structure and the production of short-chain fatty acids. He is addressing the antibacterial effects of the aloin against intestinal commensal bacterial species. Aloin has been used in dietary supplements, laxatives, weightloss supplements, beverages, beauty/cosmetics products, and vitamins. However, there is limited information available on the toxicity of these aloe products. The present study provides an evaluation of minimum inhibitory concentration (MIC) for the intestinal microbiota, which will help identify the acceptable dietary intake value for consumption of aloin/Aloe Vera in consumer products without altering the intestinal microbiome.

Dr. Gokulan is seeking to understand how the bacterial cell-wall enzymes modify the peptidoglycan layers and cell-wall components in drug/multidrug-resistance bacteria. To understand the drug resistance at the molecular level, he employs a protein homology modelling and drug-docking approach to address the drug resistance. Drug resistance could be due to mutation at the inhibitor-binding site/noninhibitor-binding site, drug inactivation, or efflux pump mechanisms. Expression of soluble protein is a prerequisite for functional characterization and drug screening for therapeutic proteins and antibodies. Towards this effort, he has established protein over-expression by using three different hosts’ expression systems. Recently he also developed a cell culture-based, high-throughput screening assay for drug discovery against antibiotic-resistant bacteria. Specifically, one of the bacterial cell-wall enzymes that is involved in peptidoglycan synthesis (L-D-Transpeptidase), which is responsible for antibiotic resistance in enzymes, over-expressed in E. coli. This over-expressed system mimics the drug-resistant bacteria. 

Dr. Gokulan’s lab is also involved in investigating knowledge-gaps associated with drug nanocrystals and their interaction with the gastrointestinal (GI) tract. Intestinal commensal bacteria play an essential role in maintaining healthy intestinal tissue, the shaping and development of immune response, and preventing the adverse effect of pathogenic bacteria. However, intestinal tissue is constantly exposed to several xenobiotic compounds, such as nanoparticles or antibiotics, as well as supplements that may cause an imbalance in commensal bacterial, gastrointestinal disturbance, and breakdown of intestinal-barrier functions. Currently, more than 750 clinical trials are in-progress involving potential nanomedicine products. Of these, 38 are approved products/currently in use and 128 are investigative new drugs (IND) applications, of which 14% are drug nanocrystals. Approximately 82% of drug nanocrystal IND applications are for oral administration. For FDA regulatory/reviewer guidance, the agency needs experimental data to assess the effect of drug nanocrystals on the human GI tract. Science-based evidences are required to understand the interaction of the GI tract with the crystal-nanodrugs, nanoparticle, and foodborne pathogens. 


Professional Societies/National and International Groups                                                         

American Society of Microbiology
Member
2012 – Present

Association of Clinical Biochemistry of India
Member
1994 – Present

Food Safety Conference
Member
2012

Indian Immunological Society
Member
1991 – Present

Tuberculosis Structural Genomic Consortium
Member
2001 – Present

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Selected Publications

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, 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.

Drug Resistance in Mycobacterium Tuberculosis and Targeting the L,D-Transpeptidase Enzyme.
Gokulan K. and Varughese K.I.
Drug Dev Res. 2018, doi: 10.1002/ddr.21455.

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, 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). pii: 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.
International Journal of Nanomedicine. 2018, 13:2857-2867.
† Contributed equally

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, DOI:10.1093.

An In Vitro Study to Assess the Impact of Tetracycline on the Human Intestinal Microbiome.
Jung J.Y., Ahn Y.B., Khare S., Gokulan K., Piñeiro S.A., and Cerniglia C.E.
Anaerobe. 2018, 49:85-94.

Effects of Residual Levels of Tetracycline on the Barrier Functions of Human Intestinal Epithelial Cells.
Gokulan K., Cerniglia C.E., Thomas C., Pineiro S.A., and Khare S.
Food and Chemical Toxicology. 2017, 109(1):253-263.

Graphene and Carbon Nanotubes Activate Different Cell Surface Receptors on Macrophages Before and After Deactivation of Endotoxins.
Lahiani M.H.†, Gokulan K.†, Williams K., Khodakovskaya M.V., and Khare S.
Journal of Applied Toxicology. 2017, 37(11):1305-1316.
† Contributed equally

Silver Ion-Mediated Killing of a Food Pathogen: Melting Curve Analysis Data of Silver Resistance Genes and Growth Curve Data.
Gokulan K., Williams K., and Khare S.
Data Brief. 2017, 11:49-53.

Assessment of Antimicrobial Effects of Food Contact Materials Containing Silver on Growth of Salmonella Typhimurium.
Williams K., Valencia L., Gokulan K., Trbojevich R., and Khare S.
Food and Chemical Toxicology. 2017, 100:197-206.

Size and Dose Dependent Effects of Silver Nanoparticle Exposure on Intestinal Permeability in an In Vitro model of the Human Gut Epithelium.
Williams K.M., Gokulan K., Cerniglia C.E., and Khare S. 
J Nanobiotechnology. 2016, 14(1):62.

Transmissible Plasmids Containing Salmonella Enterica Heidelberg Isolates Modulate Cytokine Production in Intestinal Epithelial Cells. 
Gokulan K., Khare S., Williams K. and Foley S. 
DNA and Cell Biology.  2016, 35(8):443-53.
 
Effects of Silver Nanoparticle Exposure on Intestinal Permeability in an In Vitro Model of the Human Gut Epithelium.
Williams K., Gokulan K., Cerniglia C. and Khare S.
J Nanobiotechnology. 2016, 14(1):62.  

Dose and Size Dependent Antiviral Effects of Silver Nanoparticles on Feline Calicivirus, a Human Norovirus Surrogate.
Bekele A., Gokulan K., Williams K. and Khare S.
Foodborne Pathogens and Diseases. 2016, 13(5):239-44.

Structure-Based Drug Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein.
Thakkar S., Wang X., Khaidakov M., Dai Y., Gokulan K., Mehta J. and Varughese K.
Scientific Reports from Nature Publication. 2015, 5:16740.

Cytotoxic Mechanism of Cytolethal Distending Toxin in Nontyphoidal Salmonella Serovar  (Salmonella Javiana)  During Macrophage Infection.   
Williams K., Gokulan K., Shelman D., Akiyama T., Khan A. and Khare S.
DNA and Cell Biology. 2015, 34(2);113-24.

Effects of Subchronic Exposure of Silver Nanoparticles on Intestinal Microbiota and Gut-Associated Immune Responses in the Ileum of Sprague-Dawley Rats.  
Williams K., Milner J., Boudreau M., Gokulan K., Cerniglia C. and Khare S.
Nanotoxicology. May, 9(3);279-89.

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Contact Information
Kuppan Gokulan
(870) 543-7391
Expertise
Expertise
Approach
Domain
Technology & Discipline
Toxicology