Uma Babu, Ph.D. 

Immunobiology Branch,
Division of Virulence Assessment,
Center for Food Safety and Applied Nutrition
Laurel, MD

Background:

Ph.D., University of Maryland
FDA Experience - 18 years

Research Interests:

Several food-borne pathogens cause infectious illnesses for which the immunobiology is not completely understood. These pathogens may modify functions of different immune cells, which may include secretion of inflammatory or immune cytokines or other biomarkers. The purpose of our studies is to examine the role of immunomdulators and other factors, including several commonly consumed nutrients on the immune responses and clearance of food-borne pathogens by animal tissues (in vivo) or cells (in vitro). Some of these interventions may alter colonization of animal tissues or cellular infection and clearance of pathogens. These studies will help find appropriate models for different pathogens.

Our goal includes exploring mechanism of actions of various immune modulators including vaccines and nutrients on functions of cells by using molecular biology tools. These studies may be done in collaboration with universities or other government agencies thus using expertise and resources from these organizations.

Proposed Research Project for FDA Fellow:

Assessing the impact of vitamin D enriched mushroom on tissue colonization in mice infected with Listeria. This project will include the assessment of immune biomarkers upon exposure to vitamin D enriched mushroom. Main objective is to characterize cell-mediated and innate immunity biomarkers in the mouse Listeria model.

Selected Recent Publications:

1. Uma S. Babu and Paddy W. Wiesenfeld. Nutrional and hematological effects of flaxseed. Book chapter in "Flaxseed in human nutrition", edited by Lilian U. Thompson and Stephen C. Cunnane. AOAC Press, Pp 150-173, 2003.
2. Okamura M, Lillehoj HS, Raybourne RB, Babu US, Heckert RA, Tani H, Sasai K, Baba E, Lillehoj EP. Differential responses of macrophages to Salmonella enterica serovars Enteritidis and Typhimurium. Vet Immunol Immunopathol. 107(3-4): 327-335, 2005.
3. Babu U, Dalloul RA, Okamura M, Lillehoj HS, Xie H, Raybourne RB, Gaines D, Heckert RA. Salmonella enteritidis clearance and immune responses in chickens following Salmonella vaccination and challenge. Vet Immunol Immunopathol. 101(3-4): 251-257, 2004.
4. Okamura M, Lillehoj HS, Raybourne RB, Babu US, Heckert RA, Tani H, Sasai K, Baba E, Lillehoj EP. Differential responses of macrophages to Salmonella enterica serovars Enteritidis and Typhimurium. Vet Immunol Immunopathol. 107(3-4):327-335, 2005.
5. Babu U.S., Gaines D. and Raybourne R.B. Salmonella immunobiology in chickens and role of vaccines and macrophages in bacterial clearance. Recent Res. Devel. Life Sci., 3: 203-213, 2005.
6. Babu US, Gaines DW, Lillehoj H, Raybourne RB. Differential reactive oxygen and nitrogen production and clearance of Salmonella serovars by chicken and mouse macrophages. Dev Comp Immunol. 30(10): 942-953, 2006.
7. Live attenuated Listeria monocytogenes expressing HIV Gag: immunogenicity in rhesus monkeys. Jiang S, Rasmussen RA, Nolan KM, Frankel FR, Lieberman J, McClure HM, Williams KM, Babu US, Raybourne RB, Strobert E, Ruprecht RM. Vaccine. 25(42):7470-7479, 2007.
8. Impact of dietary components on chicken immune system and Salmonella infection, Review. Uma S. Babu and Richard B. Raybourne. Expert Rev. Anti-Infect. Ther. 6(1) 121-135, 2008.
9. Zhang S, Lillehoj HS, Kim CH, Keeler CL Jr, Babu U, Zhang MZ. Transcriptional response of chicken macrophages to Salmonella enterica serovar enteritidis infection. Dev Biol (Basel). 132:141-51, 2008.
10. Babu US, Gaines DM, Wu Y, Westphal CD, Pereira M, Raybourne RB. Use of flow cytometry in an apoptosis assay to determine pH and temperature stability of shiga-like toxin 1. J Microbiol Methods. 75(2):167-71, 2008.

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Biswendu B. Goswami, Ph.D. 

Division of Molecular Biology, OARSA
Center for Food Safety and Applied Nutrition
Laurel, MD

Background:

B.S., M A College, University of Calcutta
Ph.D., University College of Science, University of Calcutta

Research Interests:

Dr. Goswami, Research Virologist, has over 30 years experience in the areas of virus –cell interaction, antivirals including Interferon response, and virus detection using molecular methods, some developed in FDA/CFSAN. Currently, he is working on the mechanism behind virus induced apoptosis mediated by a latent cellular ribonuclease called RNase L. His work shows how hepatitis A virus and some other enteric viruses following infections of host cells subvert the Interferon based cellular defense mechanism to their own advantage through the activation of RNase L.

Dr. Goswami is also working in the area of molecular detection methods for food borne viruses using an advanced array based technique, that is capable of detecting multiple viruses in the same sample, as well as identify the genotype of the virus. He has published over 40 peer-reviewed articles in these areas including eight book chapters and review articles. He is also an internationally recognized expert on the development of molecular-based methods for the detection and identification of food borne viruses using reverse transcription and PCR, and oligonucleotide array technology.

His current efforts center on the identification of closely related strains of food or water borne viruses using simultaneous detection and identification down to the strain level in one single hybridization experiment. Generally virus detection and strain identification are not run concurrently with the current most widely used molecular methods, resulting in loss of time. His laboratory is developing a high density oligonucleotide array hybridization system that incorporates thousands of oigonucleotide probes to scan a number of viral targets simultaneously. Integral to this approach are the development of closely related techniques of target synthesis using modified protocols not currently routinely used. It is believed that the project will lead to extensive improvement to array design, as well as new methods of target synthesis and labeling protocols. An additional goal is to make the protocol realistic in sensitivity that will be applicable to detection of very low concentrations of viruses in food and water samples, a main goal of the CFSAN virus detection program.

Proposed Research Project for FDA Fellow:

FDA Fellowship Program: The intern will be exposed to fundamental concepts in virology and food virology, and how this research program will enable CFSAN to better regulate food borne viral infections. The intern will also learn about modern molecular methods of virus detection and identification (typing), designing and using oligonucleotide arrays for this purpose, how to support regulatory decisions on the basis of laboratory findings.

Selected Recent Publications:

1. Goswami, B.B., Kulka, M., Ngo, D., and Cebula, T.A., 2004. Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2’-5’ oligoadenylate synthetase. Antiviral Res. 63, 153-166.
2. Bhattacharya, S.S., Kulka, M., Lampel, K.A., Cebula, T.A., and Goswami, B.B., 2004. Use of reverse transcription and PCR to discriminate between infectious and non-infectious hepatitis A virus. J. Virol. Methods. 116, 181-187.
3. Kulka, M., Chen, A., Ngo, D., Cebula, T.A. and Goswami, B.B., 2003. The cytopathic18f strain of hepatitis A virus induces RNA degradation in FrhK4 cells. Arch. Virol. 148, 1275-1300.
4. Goswami, B.B., Kulka, M., Ngo, D., Istafanos, P., and Cebula, T.A, 2002. A polymerase chain reaction based method for the detection of hepatitis A virus in produce and shellfish. J.Food Prot. 65, 393-402.
5. Smith, C.C., Nelson, J., Aurelian, L., Gober, M., and Goswami, B.B., 2000. Ras-GAP binding and phophorylation by herpes simplex virus type 2 RR1 PK (ICP10) and activation of the Ras/MEK/MAPK mitogenic pathway are required for the timely onset of virus growth. J. Virol. 74, 10417-10429.

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Michael Kulka, Ph.D. 

Research Microbiologist (Virologist)
Division of Molecular Biology
Center for Food Safety and Applied Nutrition
Laurel, MD

Background:

B.S., Albright College
Ph.D., Department of Microbiology and Immunology, Medical College of Pennsylvania

Research Interests:

Dr. Michael Kulka, Research Microbiologist, has over 20 years combined experience in the areas of molecular and cellular biology, molecular virology, and antiviral/immune modification. Upon his arriving at the FDA and joining the Molecular Virology Team (MVT), he applied his knowledge and experience to the team’s research aims which focus on the improvement of genomic detection and development of culture methods for foodborne viruses. He has published over 25 peer-reviewed articles, co-authored a book chapter and is recognized for scientific contributions in his field of research. His laboratory has had both intra- and extramural research collaborations and has also made significant contributions in other division and center related issues such as participation in pre-validation round robin testing, application of experimental methods to outbreak samples/investigation, and contribution to the development of Risk Profile (CFSAN) documents on hepatitis A virus and norovirus.

Proposed Research Project for FDA Fellow:

The isolation of foodborne viruses from various food matrices and subsequent detection by genomic methods (e.g., microarray based detection following polymerase-based genomic amplification) are part of the ongoing research and methods development by the MVT.  However, current genomic based methods do not readily nor directly address the issue of virus infectivity.  This issue may addressed through application of other methods such as cell culture infection with subsequent confirmation of virus growth and replication.   However, current cell culture methods for certain foodborne viruses (e.g., hepatitis A virus and norovirus) are not particularly amenable for the rapid detection of infectious virus.  For example, hepatitis A virus replicates very slowly in culture without cytopathogenicity and its replication is restricted to a limited number of primate cell lines.  While growth rates are improved with adaptation of the virus to cell culture, this requires a protracted period of virus inoculation/passage and sub-culturing.  Additionally, there are currently no established culture methods for norovirus. 

This project will focus on investigating the contribution of certain cellular and viral genes (concomitant with ongoing investigations of relevant biomolecular pathways, e.g., protein kinase signaling and apoptosis pathways) to the restricted growth and phenotype of wild-type and mutant foodborne virus strains in selected cell lines.  The fellow will gain an understanding of basic virology and cell culture principles, recombinant viral and cellular gene expression, as well as the development and application of molecular techniques important to understanding the growth rate and phenotype restriction of foodborne virus replication in culture.

Selected Recent Publications:

1. Goswami, B.B., Kulka, M., Ngo, D., Cebula, T.A., 2004. Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2'-5' oligoadenylate synthetase. Antiviral Res. 63, 153-166.
2. Kulka, M., Chen, A., Ngo, D., Bhattacharya, S.S., Cebula, T.A., Goswami, B.B., 2003. The cytopathic 18f strain of hepatitis A virus induces RNA degradation in FRhK-4 cells. Arch. Virol. 148, 1275-1300.

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Dan D. Levy, Ph.D. 

Acting Supervisor, New Dietary Ingredient Review Team
Office of Nutrition, Labeling and Dietary Supplements
Center for Food Safety and Applied Nutrition
College Park, MD

Background:

A.B., Chemistry, Oberlin College
M.S./Ph.D., Sackler Institute of Graduate Biomedical Studies, New York University

Research Interests:

Dr. Levy is a molecular biologist with a broad range of interests the application of molecular genetic techniques to problems of regulatory interest. He chairs the Genetic Toxicology Working Group of the Interagency Coordinating Committee for Validation of Alternative Methods and the FDA inter-center working group on live microbial ingredients in FDA regulated products. He transferred from a laboratory research position 5 years ago into a regulatory position. In the last year he has initiated projects within FDA laboratories to advance validation of the Comet assay and to establish methods for genetic identification of Lactobacillus and Bacillus strains used as ingredients in dietary supplements.

Proposed Research Project for FDA Fellow:

Lactobacilli are increasingly appearing in dietary supplements sold for their probiotic properties yet there is no established paradigm for evaluating the safety of these organisms. In particular, while many Lactobacilli show resistance to clinically significant antibiotics and there is documentation of horizontal transfer between Lactobacilli and an Enterococcus, there have been few studies of the mechanisms of resistance to antibiotics in Lactobacilli or to evaluate the risk or lack of risk of horizontal transfer of antibiotic resistance from strains used as food ingredients to pathogenic gut microbiota. The primary duties of the Fellow will be to propose and carry out an investigation of the mechanisms of resistance to a clinically significant antibiotic (or antibiotic class) and develop an assay to evaluate its transfer to one or more genera that are part of the gastrointestinal microbiota. This project will be developed in collaboration with the CFSAN Molecular Genetics Branch laboratories. The Fellow will also participate in regulatory review of the safety of live microbial ingredients that have been proposed for use in dietary supplement products.

Selected Recent Publications:

1. Levy, D.D., Sharma, B. and Cebula, TA. Single Nucleotide Polymorphism Mutation Spectra and Resistance to Quinolone Antibiotics in Salmonella with a Mutator Phenotype. Antimicrobial Agents and Chemotherapy, 48: 2355-63, 2004.
2. Chizhikov, V., Rasooly, A., Chumakov, K., and Levy, D.D. Microarray Analysis of Microbial Virulence Factors, Environmental and Applied Microbiology 67: 3258-63, 2001.
3. Levy, D.D. and Cebula, T.A. Fidelity of replication of repetitive DNA in mutS and repair proficient Escherichia coli. Mutation Research 474: 1-14, 2001

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MaryAnn Principato, Ph.D. 

Immunotoxicology Section/ DivisionToxicology
Center for Food Safety and Nutrition
Laurel, MD

Background:

B.A., Natural Sciences, Fordham University, New York
M.S., Biochemistry, New York University Basic Medical Sciences, New York
Ph.D., Pathobiology, College of Physicians and Surgeons of Columbia University

Research Interests: 

This laboratory has maintained a dual focus upon Staphylococcal enterotoxin B as a superantigen and food contaminant. The research in my laboratory concerns the fundamental events that regulate T cell activation and development during immune responses to super antigenic stimulation by the pyrogenic food toxin, Staphylococcal enterotoxin B (SEB). Efforts have focused on understanding and describing the basic cellular and molecular events triggered following ingestion of the superantigen, and the consequences of this exposure upon health and autoimmunity induction using mouse models of autoimmune disease and aging. Our other emphasis in the laboratory has centered upon the protection and defense of the national food supply. To this end, we developed a variety of methods for the rapid assay and identification of Staphylococcal enterotoxin B in a wide variety of food matrices. In other studies, we have shown that the detection of SEB in thermally processed foods can alter the toxin’s ability to be detected by conventional antigen-capture ELISA. To this end, we have developed an in vivo assay for the detection of occult SEB toxin in thermally processed foods.

Proposed Research Project for FDA Fellow: 

The Fellow will develop a complementary approache to existing projects that rely on molecular and biochemical approaches for the analysis of SE-induced T cell receptor –mediated signaling cascades and other SEB-induced gene expression patterns in tissues derived after the ingestion of SEB or SEA-tainted foods. The goal is to identify gene subset(s) that can be used as indicators of toxin exposure and exploit the markers in the development of in vitro assays for toxin detection.

The Fellow will gain research experience within the areas of receptor-mediated signaling cascades and superantigen-induced changes in the mammalian immune system.  The molecular and cellular biomarker data obtained in this study will be assessed for its value as indicator of SE contamination in foods.

Selected Recent Publications:

1. Mary Ann Principato, Andrei Perlloni, J. M. Njoroge, R. L. Jones, Jr., T. Boyle. Detection and Recovery of Surrogate Target IL-2 Protein with ELISA when using Milk, Orange juice, or Carbonated Beverages as a Food Matrix. J. AOAC Int. accepted for publication. 2008
2. Joan E. Roberts, Barbara M. Kukielczak, Colin F. Chignell, Robert H. Sik, Dan-Ning Hu, Mary Ann Principato. Simulated microgravity induced damage in human retinal pigment epithelial cells. Molecular Vision 12:633-8 2006
3. M.A. Principato, et. al. Tissue-Specific Immune Responsiveness to Staphylococcal Enterotoxin in the Aged Gut Lymphatics. FASEB Journal.13:4 March 1999
4. Glycoconjugate Expression in Mouse Peripheral and Gut-Associated Lymphocytic Populations. M.A. Principato, B.D. Lawless, K. Reese, G. Roth, A. Formen. J. Allergy & Clinical Immunology. 1997
5. MaryAnn Principato, Thomas Boyle, Joyce Njoroge, Robert L. Jones, Jr., Michael O’Donnell. Effect of Thermal Processing during Yogurt Production upon the Detection of Staphlyococcal enterotoxin B. Submitted J Food Protection 2008

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Debra A. Street, Ph.D., M.P.H. 

Chief, Emergency Response and Surveillance Branch
OFDCER/Division of Public Health
Center for Food Safety and Applied Nutrition
College Park, Maryland

Background:

B.A., English
M.P.H., Epidemiology
Ph.D., Epidemiology
FDA Experience - 15 years

Research Interests:

Characterization of adverse events reported by passive surveillance
Incidence and prevalence of infectious disease
Risk assessment for food contamination as associated with chronic disease

Proposed Research Project for FDA Fellow:

The proposed research involves analyzing adverse event reports from the CFSAN Adverse Event Reporting Systems (CAERS). CAERS collects reports of adverse health effects associated with foods, dietary supplements, or cosmetics. Reports to CAERS come from consumers, manufacturing firms, health professionals, state and local government agencies, and others who report individual illnesses to the FDA District Offices, through FDA’s MedWatch program, or directly to CAERS via e-mail, phone, fax, or regular mail.

The Fellow will develop 2 projects, utilizing information from CAERS. The first project will involve analysis of energy drinks and the characterization of the adverse events associated with these drinks. The second project with CAERS data will be determined in conjunction with the Center for Food Safety and Applied Nutrition’s Program Offices by the Fellow. In addition to these projects, the Fellow will consider new approaches and methods for analyzing passive surveillance data.

Selected Recent Publications:

1. Ross MP, Ferguson M, Street D, Klontz K, Schroeder T, Luccioli S. Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J allergy Clin Immunol 2008; 121(1):166-171.
2. Vierk KA, Koehler KM, Fein SB, Street DA. Prevalence of self-reported food allergy in American adults and use of food labels. JACI 2007; 119: 1504-1510.
3. Joint FAO/WHO Expert Committee on Food Additives, 67th meeting, Rome 20-29 June 2006, Summary and Conclusions.
4. Klontz KC, Timbo BB, Street DA. Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). Ann Pharmacotherapy 2006; 40:1747-51.
5. Wong S, Street D, Delgado SI, Klontz KC. Recalls of food and cosmetics due to microbial contamination reported to the U.S. Food and Drug Administration. J Food Protect 2000; 63:1113-1116.
6. Street DA, Javitt JC, Wang Q, Tielsch JM, Canner JK, Bass EB, Steinberg EP on behalf of the Cataract Patient Outcomes Research Team. Atherosclerosis in patients undergoing cataract extraction: a nationwide case-control study. Arch Ophthalmol 1996; 114:1407-11.
7. Altekruse SF, Street DA, Fein SB, Levy AS. Consumer knowledge of food borne microbial hazards and food-handling practices. J Food Protection 1995; 59: 287-294.
8. Street DA, Comstock GW, Salkeld RM, Schüep W, Klag MJ. Serum antioxidants and myocardial infarction: are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction? Circulation 1994; 90:1154-1161.
9. Street DA, Javitt JC. National outcomes of cataract extraction IV: five-year mortality following inpatient cataract surgery. Am J Ophthalmology 1992; 113:263-268.
10. Street DA, Vinokur ET, Waring GO III, Pollack SJ, Clements SD, Perkins JV. Lack of association between keratoconus, mitral valve prolapse, and joint hypermobility. Ophthalmology 1991; 98:170-176.

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