Dipika Gupta, Ph.D.
Associate Professor of Biochemistry and Molecular Biology
Course Director Step 1 The Molecular Basis of Medicine
- University of Poona, India, 1981 B.Sc.; Zoology
- University of Poona, India, 1983 M.Sc.; Animal Physiology
- Clemson University, Clemson, South Carolina. 1990 Ph.D.; Biochemistry
- North Carolina State University, Raleigh, North Carolina, 1991-1992
- Northwest Center for Medical Education, Gary, Indiana, 1992-1993
Dr. Gupta's research is focused on elucidating the molecular mechanisms of innate immunity to bacteria. Innate immunity is the first line of defense against infections and is present in all animals.
Dr. Gupta's research group, in collaboration with Dr. Dziarski identified a new family of proteins present in humans. These proteins are called Peptidoglycan Recognition Proteins (PGRPs), because they bind to peptidoglycan, an essential component of the outer surface of all bacteria. Dr. Gupta's and Dr. Dziarski's groups cloned the genes for human peptidoglycan recognition proteins, identified cell types that express the different PGRPs and have identified the in vitro and in vivo functions of these proteins.
These proteins are expressed in eosinophils, neutrophils and macrophages or in epithelial cells from different tissues, including skin, eyes, mouth, throat, esophagus, and liver. PGRPs are antibacterial, i.e., they kill bacteria and one of the PGRP’s is also an enzyme that degrades peptidoglycan and thus prevents some of the harmful effects caused during bacterial infections.
PGRPs protect the host from inflammatory diseases, such as colitis, psoriasis, atopic dermatitis and asthma. PGRPs are important in maintaining beneficial normal bacterial flora in the intestinal tract. The proper balance in the intestinal bacterial flora (probiotics) is important, because it protects the host from developing intestinal inflammatory diseases, such as ulcerative colitis, asthma, and obesity. Genetic variants in PGRP genes significantly associate with sensitivity to inflammatory bowel disease in patients.
The research on the role of PGRPs in maintaining healthy microbiome and protecting the host against intestinal inflammation, skin diseases, asthma, and obesity will offer opportunities to design new approaches for the prevention and treatment of these inflammatory diseases.
Selected Research Papers
1. Gupta, D, Jin, Y, and Dziarski, R. 1995. Peptidoglycan induces transcription and secretion of TNF-alpha and activation of lyn, ERK, and rsk signal transduction proteins in mouse macrophages. Journal of Immunology 155:2620-2630, PMID: 7650392
2. Gupta, D, Kirkland, TN, Viriyakosol, S, and Dziarski, R.1996. CD14 is a cell-activating receptor for bacterial peptidoglycan. Journal of Biological Chemistry, 271:23310-23316, PMID: 8798531
3. Gupta, D, Wang, Q, Vinson C, and Dziarski, R. 1999. Bacterial peptidoglycan induces CD14-dependent activation of transcription factors CREB/ATF and AP-1. Journal of Biological Chemistry, 274:14012-14020, PMID: 10318814
4. Dziarski, R, Wang, Q, Miyake, K, Kirschning, C, and Gupta, D. 2001. MD-2 enables Toll-like receptor-2 (TLR2)-mediated responses to LPS and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components. Journal of Immunology, 166:1938-1944, PMID: 11160242
5. Liu, C, Xu, Z, Gupta, D, and Dziarski, R. 2001. Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. Journal of Biological Chemistry, 276:34355-35222 (featured on the cover of September 14 issue), PMID: 11461926
6. Xu, Z, Dziarski, R, Wang, Q, Swartz, K, Sakamoto, KM, and Gupta, D. 2001. Bacterial peptidoglycan-induced tnf-alpha transcription is mediated through the transcription factors Egr-1, Elk-1, and NF-kappaB. Journal of Immunology, 167:6975-6982, PMID: 11739517
7. Dziarski, R, Platt, KA, Gelius, E, Steiner, H, and Gupta, D. 2003. Defect in neutrophil killing and increased susceptibility to infection with non-pathogenic Gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice. Blood, 102: 689-697 (featured in an editorial: Inside Blood), PMID: 12649138
8. Wang, Z-M, Li, X, Cocklin, RR, Wang, M, Wang, M, Fukase, K, Inamura, S, Kusumoto, K, Gupta, D, and Dziarski, R. 2003. Human peptidoglycan recognition protein-L (PGRP-L) is an N-acetylmuramoyl-L-alanine amidase. Journal of Biological Chemistry, 278:49044-49052, PMID: 14506276
9. Lu, X, Wang, M, Qi, J, Wang, H, Li, X, Gupta, D, and Dziarski, R. 2006. Peptidoglycan recognition proteins are a new class of human bactericidal proteins. Journal of Biological Chemistry, 281:5895-5907, PMID: 16354652
10. Li, X, Wang, S, Wang, H, and Gupta, D. 2006. Differential expression of peptidoglycan recognition protein 2 in the skin and liver requires different transcription factors. Journal of Biological Chemistry, 281:20738-20748, PMID: 16714290
11. Li, X, Wang, S, Qi, J, Echtenkamp, SF, Chatterjee, R, Wang, M, Boons, G-B, Dziarski, R, and Gupta, D. 2007. Zebrafish peptidoglycan recognition proteins are bactericidal amidases essential for defense against bacterial infections. Immunity, 27:518-527, PMID: 17892854
12. Gupta, D. 2008. Peptidoglycan recognition proteins-maintaining immune homeostasis and normal development. Cell Host & Microbe, 15:273-274, (invited preview) PMID: 18474351
13. Saha, S, Qi, J, Wang, S, Wang, M, Li, X, Kim, Y-G, Nunez, G, Gupta, D, and Dziarski, R. 2009. PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation. Cell Host and Microbe, 5:137-150, PMID: 19218085
14. Saha, S, Jing, X, Park, SH, Wang, S, Li, X, Gupta, D, and Dziarski, R. 2010. Peptidoglycan recognition proteins protect mice from inflammatory bowel disease by promoting normal gut flora and preventing induction of interferon-gamma. Cell Host and Microbe, 8:147-162. PMID: 20709292
15. Kashyap, DR, Wang, M, Liu, L-H, Boons, G-J, Gupta, D, Dziarski, R. 2011. Peptidoglycan Recognition Proteins kill bacteria by activating protein-sensing two-component systems. Nature Medicine, 17:676-683 (featured in a Commentary in the same issue of the journal). PMID: 21602801
16. Park, SY, Gupta, D, Kim, CH, and Dziarski, R. 2011. Differential effects of peptidoglycan recognition proteins on experimental atopic and contact dermatitis mediated by Treg and Th17 cells. PLoS One, 6: e24961. p. 1-16, doi: 10.1371/journal.pone.0024961. PMID: 21949809
17. Park, SY, Gupta, D, Hurwich, R, Kim, CH, and Dziarski, R. 2011. Peptidoglycan recognition protein Pglyrp2 protects mice from psoriasis-like skin inflammation by promoting regulatory T cells and limiting Th17 responses. Journal of Immunology, 187: 5813-5823. PMID: 22048773
18. Park SY, Jing X, Gupta D, Dziarski R. 2013. Peptidoglycan recognition protein 1 enhances experimental asthma by promoting Th2 and Th17 and limiting regulatory T cell and plasmacytoid dendritic cell responses. Journal of Immunology, 190:3480-3492, PMID: 23420883
19. Zulfiqar F, Hozo I, Rangarajan S, Mariuzza R, Dziarski R, Gupta D. 2013. Genetic association of peptidoglycan recognition protein variants with inflammatory bowel disease. PLoS One, 8: e67393, p.1-14, doi:10.1371/journal.pone.0067393. PMID: 23840689
20. Kashyap DR, Rompca A, Gaballa A, Helmann JD, Chan J, Chang CJ, Hozo I, Gupta D, Dziarski. R. 2014. Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress. Plos Pathogens, 10: e1004280, doi: 10.1371/journal.ppat.1004280. PMID: 25032698
21. Jing X, Zulfiqar F, Park SY, Nunez G, Dziarski R, Gupta D. 2014. Peptidoglycan recognition protein 3 and Nod2 synergistically protect mice from dextran sodium sulfate-induced colitis. Journal of Immunology, 193: 3055-3069. PMID: 25114103
1. Dziarski, R, and Gupta, D. 1999. Function of CD14 as a peptidoglycan receptor: differences and similarities with LPS. Journal of Endotoxin Research, 5:56-61
2. Dziarski, R, Ulmer, AJ, and Gupta, D. 2000. Interactions of CD14 with components of Gram-positive bacteria. Chemical Immunology, 74:83-107, PMID: 10608083
3. Dziarski, R, and Gupta, D. 2000. Role of MD-2 in TLR2- and TLR4-mediated recognition of gram-negative and gram-positive bacteria and activation of chemokine genes. Journal of Endotoxin Research, 6:401-405, PMID: 11521063
4. Dziarski R, Gupta D. 2005. Peptidoglycan recognition in innate immunity. Journal of Endotoxin Research, 11:304-10, PMID: 16263004
5. Dziarski, R, and Gupta, D. 2006. Mammalian PGRPs: novel antibacterial proteins. Cellular Microbiology, 8:1059-1069, PMID: 16819960
6. Dziarski, R, and Gupta, D. 2006. The peptidoglycan recognition proteins (PGRPs). Genome Biology, 7:232.1-13, PMID: 16930467
7. Royet, J, Gupta, D, and Dziarski, R. 2011. Peptidoglycan recognition proteins: modulators of the microbiome and inflammation. Nature Reviews Immunology, 11:837-851. PMID: 22076558
8. Dziarski, R, Kashyap DR, and Gupta, D. 2012. Mammalian peptidoglycan recognition proteins kill bacteria by activating two-component systems and modulate microbiome and inflammation. Microbial Drug Resistance, 18:280-285. PMID: 22432705