Chhinder Sodhi, Ph.D.

Headshot of Chhinder Sodhi
  • Assistant Professor of Surgery

Background

Dr. Chhinder Sodhi is an assistant professor of surgery at the Johns Hopkins University School of Medicine.  His research focuses on the role of Toll-like receptors (TLRs) in the pathogenesis of the deadly disease of premature infants called Necrotizing Enterocolits (NEC), and understanding the mechanisms by which major blunt trauma leads to remote organ injury. 

He also earned an undergraduate degree, MSc, and PhD from Punjab University in Chandigarh, India. He completed a postdoctoral fellowship at Punjab University as well as Northwestern University in Chicago, Illinois and the Medical College Wisconsin in Milwaukee, Wisconsin.

Dr. Sodhi is a member of the David Hackam’s laboratory, which focuses on necrotizing enterocolitis (NEC), a devastating disease of premature infants and the leading cause of death and disability from gastrointestinal disease in newborns.

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Titles

  • Assistant Professor of Surgery

Departments / Divisions

Education

Degrees

  • Ph.D.; Postgraduate Institute of Medical Education and Research (India) (1996)

Research & Publications

Research Summary

The major focus of my research is to study the role of Toll-like receptors (TLRs) in the pathogenesis of the deadly disease of premature infants called Necrotizing Enterocolits (NEC), and understanding the mechanisms by which major blunt trauma leads to remote organ injury. 

Lab

Lab Website: The Hackam Lab

Selected Publications

 

  1. Sodhi, C. P., Rana, S.V., Mehta, S.K., Vaiphei, K., Attri, S., Thakur, S., & Mehta S. Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition.Journal of Biochemical & Molecular Toxicology, 11(3): 139-146, 1996. PMID: 8906429
  2. Rana, S., Sodhi, C. P., Mehta, S., Vaiphei, K., Katyal, R., Thakur, S., & Mehta, S. K. Protein-energy malnutrition and oxidative injury in growing rats. Human & Experimental Toxicology, 15(10): 810-814, 1996. PMID: 8906429
  3. Sodhi, C. P., Katyal, R., Rana, S. V., Attri, S., & Singh, V. Study of oxidative-stress in rotavirus infected infant mice. Indian Journal of Medical Research, 104: 245-249, 1996. PMID: 8952176
  4. Katyal, R., Desigan, B., Sodhi, C. P., & Ohja, S. Oral aluminum administration and oxidative injury.Biology Trace Element Research, 57: 125-30, 1997. PMID: 9282259
  5. Sodhi, C. P., Rana, S., Mehta, S., Vaiphei, K., Goel, R.C., & Mehta, S.K.Study of oxidative-stress in rifampicin-induced hepatic in young rats with protein-energy malnutrition. Human & Experimental Toxicology, 16: 315-21,1997. PMID: 9219027
  6. Sodhi, C. P., Rana, S. V., Mehta, S.K., Vaiphei, K., Attri, S., & Mehta, S. Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats. Drug & Chemical Toxicology, 20: 255-69,1997. PMID: 9292280
  7. Bansal, D., Sodhi, C.P., Mahmood, S., & Mahmood, A. Effect of chronic ethanol feeding on intestinal alkaline phosphatase activity in rats. Indian Journal of Medical Research, 107:118-122, 1998. PMID: 9599950
  8. Sodhi, C. P., Rana, S.F., Attri, S., Mehta, S., Yaiphei, K., & Mehta, S.K. Oxidative-hepatic injury of isoniazid-rifampicin in young rats subjected to protein and energy malnutrition. Drug & Chemical Toxicology, 21: 305-317, 1998. PMID: 9706463
  9. Gill, R. K., Mahmood, S., Sodhi, C.P., Nagpaul, J.P., & Mahmood, A. IgG binding and expression of its receptor in rat intestine during postnatal development. Indian Journal of Biochemistry Biophysics, 36: 252-57,1999. PMID: 10650727
  10. Sodhi, C.P., Battle, D., & Sahai, A. Osteopontin mediates hypoxia-induced proliferation of cultured mesangial cells: role of PKC and p38 MAPK. Kidney International, 58(2): 691-700, 2000. PMID: 10916092
  11. Attri, S., Rana, S.V., Vaiphei, K., Sodhi, C.P., Katyal, R., Goel, R.C., Nain, C.K., & Singh K. Isoniazid and rifampicin-induced oxidative hepatic injury – protection by N-acetylcysteine. Human & Experimental Toxicology, 19: 517-22, 2000. PMID: 11204554
  12. Sodhi, C.P., Phadke, S.A., Battle, D., & Sahai, A. Hypoxia and high glucose cause exaggerated mesangial cell growth and collagen synthesis: role of osteopontin. American Journal of Physiology & Renal Physiology, 280: F667-74, 2001. PMID: 11249858
  13. Sodhi, C.P., Phadke, S.A., Battle, D., & Sahai, A. Hypoxia stimulates osteopontin expression and Proliferation of cultured vascular smooth muscle cells: potentiation with high glucose. Diabetes. 50(6): 1482-1490, 2001. PMID: 11375351
  14. Attri, S., Rana, S.V., Vaiphie, K., Katyal, R., Sodhi, C.P., Kanwar, S., & Singh K. Protective effect of N-acetylcysteine in isoniazid induced hepatic injury in growing rats. Indian Journal of Experimental Biology, 39(5): 436-40, 2001. PMID: 11375351
  15. Mahmood, S., Sodhi, C.P., & Ganguly, N.K. Expression of sodium-glucose co-transporter and brush border disaccharidases in Giardia lamblia infected rat intestine. Indian Journal of Biochemistry & Biophysics, 39: 185-90, 2002. PMID: 22905389
  16. LaPointe, M.S., Sodhi, C., Sahai, A., & Battle, D. Na+/H+ exchange activity and NHE-3 expression in renal tubules from the spontaneously hypertensive rat. Kidney International, 62(1): 157-65, 2002. PMID: 12081574
  17. Sahai, A., & Sodhi, C. P. Hypoxia potentiates Ang II and PDGF-Induced Stimulation of Osteopontin Expression and Proliferation in Cultured VSM Cells. The Scientific World. ElSBN 1-931831-04-1; DOI 10.1100/tsw. 2002. 260.
  18. Sodhi, C.P., Kanwar, Y.S., & Sahai, A. Hypoxia and high glucose upregulate AT1 receptor expression and potentiate Ang II-induced proliferation in VSM cells. American Journal of Physiology, Heart Circulation & Physiology, 284 (3): H846-H852, 2003. PMID: 12433659
  19. Sodhi, C.P., Rampalli, S., Perez, R.G., Koo, E.H., & Gottardi-Littell, N.R. The endocytotic pathway is required for the increased A42 secretion during apoptosis. Molecular Brain Research, 128: 201-11, 2004. PMID: 15363895
  20. Sodhi, C.P, Li, J., & Duncan, S.A. Generation of conditional knockout of GATA6. BMC Developmental Biology 6:19, 2006. PMID: 16611361
  21. Anand, R. J., Gribar, S. C., Li, J., Kohler, J. W., Branca, M. F., Dubowski, T., Sodhi, C.P., & Hackam, D. J. Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1alpha-dependent manner. Journal of Leukocyte Biology, 82(5), 1257-1265, 2007. PMID: 17675562
  22. Leaphart, C. L., Cavallo, J., Gribar, S. C., Cetin, S., Li, J., Branca, M. F., Sodhi, C.P., & Hackam, D. J. A critical role for TLR4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. Journal of Immunology, 179, 4808-20, 2007. PMID: 17878380
  23. Anand, R. J., Dai, S., Rippel, C., Leaphart, C., Qureshi, F., Gribar, S. C., Kohler, J., Sodhi, C.P., & Hackam, D. J. Activated macrophages inhibit enterocyte gap junctions via the release of nitric oxide.American Journal of Physiology, Gastrointestinal Liver Physiology, 294, G109-19, 2007. PMID: 17975131
  24. Gribar, S. C., Anand, R. J., Sodhi, C. P., & Hackam, D. J. The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation. Journal of Leukocyte Biology, 83(3), 493-498, 2008, review. PMID: 18160540
  25. Sodhi, C.P., Perez, R.G., & Gottardi-Littell, N.R. Phosphorylation of beta-amyloid precursor protein (APP) cytoplasmic tail facilitates amyloidogenic processing during apoptosis. Brain Research, 1198:204-212, 2008. PMID: 18275940
  26. Luebke-Wheeler, J., Zhang, K., Battle, M., Si-Tayeb, K., Garrison, W., Sodhi, C., Li, J., Kaufman, R.N., & Duncan, S.A. Hepatocyte nuclear factor 4alpha is implicated in endoplasmic reticulum stress-induced acute phase response by regulating expression of cyclic adenosine monophosphate responsive element binding protein H. Hepatology, 48:1242-1250, 2008. PMID: 18704925
  27. Mollen, K.P., Gribar, S. C., Anand, R. J., Kaczorowski, D.J., Kohler, J.W., Branca, M.F., Dubowski, T.D., Sodhi, C.P., & Hackam, D.J. Increased expression and internalization of the endotoxin coreceptor CD14 in enterocytes occur as an early event in the development of experimental necrotizing enterocolitis. Journal of Pediatric Surgery, 43, 1175-81, 2008. PMID: 18558203
  28. Gribar, S. C., Richadson, W.M., Sodhi, C.P., & Hackam, D. J. No longer an innocent bystander: epithelial toll-like receptor signaling in the development of mucosal inflammation. Molecular Medicine, 9-10: 645-49, 2008 (review). PMID: 18584047
  29. Leaphart, C. L., Dai, S., Gribar, S. C., Richardson, W., Ozolek, J., Shi, X.H., Burns, J.R., Branca, M. F., Li, J., Weisz, O.A., Sodhi, C., & Hackam, D. J. Interferon-gamma Inhibits Enterocyte migration by Reversibly Displacing Connexin-43 from Lipid Rafts. American Journal Physiology Gastrointestinal Liver Physiology, 295: G559-69, 2008. PMID: 18635599
  30. Sodhi, C, Richardson, W., Gribar, S., & Hackam , D.J. The development of animal models for the study of necrotizing enterocolitis. Disease Model Mechanisms, 1(2-3): 94-8. 2008 (review). PMID: 19048070
  31. Anand, R.J., Dai, S., Gribar, S.C., Richardson, W., Kohler, J.W., Hoffman, R.A., Branca, M.F., Li, J., Shi, X.H., Sodhi, C.P., & Hackam, D.J. A role for connexin43 in macrophage phagocytosis and host survival after bacterial peritoneal infection. Journal of Immunology, 181(12): 8534-8543, 2008. PMID: 19050272
  32. Gribar S, C., Sodhi, C.P., Richardson, W.M., Anand, R.J., Gittes, G.K., Branca, M.F., Jakub, A., Shi, X.H., Shah, S., Ozolek, J.A., & Hackam, D.J. Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and treatment of necrotizing enterocolitis. Journal of Immunology, 182:636-646, 2009. PMID: 19109197
  33. Sodhi, C.P., Shi, X.H., Richardson W.M., Grant, Z.S., Shapiro, R.A., Prindle, T Jr., Branca, M., Russo, A., Gribar, S.C., Ma, C., & Hackam, D.J. Toll-like Receptor-4 Inhibits Enterocyte Proliferation via Impaired beta-Catenin Signaling in Necrotizing Enterocolitis. Gastroenterology, 138: 185-196, 2010. PMID: 19786028
  34. Dai, S, Sodhi, C.P., Cetin, S., Richardson, W, Branca M, Neal MD, Prindle T, Ma C, Shapiro RA, Li B, Wang JH, Hackam DJ. Extracellular high mobility group box1 (HMGB1) inhibits enterocyte migration via activation of toll like receptor 4 and increased cell-matrix adhesiveness. Journal of Biological Chemistry, 2009, 285: 4995-5002. PMID: 20007974
  35. Richardson, W.M., Sodhi, C.P., Russo, A., Siggers, R.H., Afrazi, A., Gribar, S.C., Neal, M.D., Dai, S., Prindle, T.Jr., Branca, M., Ma, C., Ozolek, J., & Hackam, D.J.Nucleotide-binding oligomerization domain-2 inhibits toll-like receptor-4 signaling in the intestinal epithelium.Gastroenterology. 139: 904-917, 2010. PMID: 20580721
  36. Neal, M.D., Richardson, W.M., Sodhi, C.P., Russo, A., & Hackam, D. J. Intestinal stem cells and their roles during mucosal injury and repair. Journal of Surgery Research, 167: 1-8, 2011 (review). PMID: 20599211
  37. Afrazi, A., Sodhi C. P., Richardson, W., Neal, M., Good, M., Siggers, R., & Hackam, D. J. New insights into the pathogenesis and treatment of necrotizing enterocolitis: Toll-like receptors and beyond.Pediatric Research, 69: 183-8, 2011 (review). PMID: 21135755
  38. Sodhi, C., Levy, R., Gill, R., Neal, M.D., Richardson, W., Branca, M., Russo, A., Prindle. T., Billiar, T.R., & Hackam, D.J. DNA attenuated enterocyte Toll-like receptor 4 mediated injury after remote Trauma.American Journal of Physiology Gastrointestinal Liver Physiology, 300 (5): G862-73, 2011, 2011. PMID: 21233273
  39. Afrazi, A., Sodhi, C.P., Good, M., Jia, H., Siggers, R., Yazji, I., Ma, C., Neal, M.D., Prindle, T., Grant, Z.S., Branca, M.F., JOzolek, J., Chang, E.B., & Hackam, D.J. Intracellular Heat Shock Protein-70 negatively regulates TLR4 signaling in the newborn intestinal epithelium. Journal of Immunology, 188: 4543-4557, 2012. PMID: 22461698
  40. Yi, H., Patel, A.K., Sodhi C.P., Hackam, D.J., & Hackam. A.S. Novel role for the innate immune receptor Toll-like receptor 4 (TLR4) in the regulation of the Wnt signaling pathway and photoreceptor apoptosis. PLoS One. 7(5): e36560, 2012. PMID: 22615780
  41. Good, M., Siggers, R.H., Sodhi, C. P., Afrazi, A., Alkhudari. F., Egan, C.E., Neal, M.D., Yazji, I., Jia, H., Lin, J., Branca MF, Ma C, Prindle T, Grant Z, Shah S, Slagle D 2nd, Paredes J, Ozolek J, Gittes GK, Hackam DJ.Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium. Proceeding of National Academy of Sciences U S A. July 10; 109(28): 11330-11335, 2012. PMID: 22733781
  42. Li, H.H., Li, Q., Liu, P., Liu, Y., Li, J., Wasserloos, K., Chao, W., You, M., Oury, T.D., Sodhi, C., Hackam DJ, Billiar TR, Leikauf GD, Pitt BR, Zhang LM. WNT1-Inducible Signaling Pathway Protein 1 Contributes to Ventilator-Induced Lung Injury. American Journal of Respiratory, Cell Molecular Biology, 47: 528-35, 2012. PMID: 22700866
  43. Sodhi, C.P., Neal, M.D., Siggers, R., Sho, S., Ma C, Branca MF, Prindle T Jr, Russo AM, Afrazi A, Good M, Brower-Sinning R, Firek B, Morowitz MJ, Ozolek JA, Gittes GK, Billiar TR, Hackam DJ. Intestinal epithelial Toll-like receptor 4 regulates goblet cell development and is required for necrotizing enterocolitis in mice. Gastroenterology, 143 (3): 708-718, 2012. PMID: 22796522
  44. Neal, M.D., Sodhi, C.P., Jia, H., Dyer, M., Egan, C., Yazji, I., Good, M., Afrazi, A., Marino, R., Slagle, D., Ma, C., Branca, M.F., Prindle, T., Grant, Z., Ozolek, J., & Hackam, D.J. Toll like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53-upregulated modulator of apoptosis. Journal of Biological Chemistry, 287 (44): 37296-37308, 2012. PMID: 22955282
  45. Neal, M.D., Sodhi, C.P., Dyer, M., Craig, B.T., Good, M., Jia, H., Yazji, I., Afrazi, A., Richardson, W.D., Beer-Stolz, D., Marino, Prindle, T.,Grant, Z., Branca, M.F., Ozolek, J., & Hackam, D.J. A Critical Role for Toll-like Receptor-4 Induction of Autophagy in the Regulation of Enterocyte Migration and the Pathogenesis of Necrotizing Enterocolitis. Journal of Immunology, 190: 3541-3551, 2013. PMID: 23455503
  46. Nace, G.W., Huang, H., Klune, J.R., Eid, R.E., Rosborough, B.R., Korff, S., Li, S., Shapiro, R.A., Stolz, D.B., Sodhi, C.P., Hackam, D.J., Geller, D.A., Billiar, T.R and Tsung, A. Cellular specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury. Hepatology, 58: 374-87, 2013. PMID: 23460269
  47. Deng, M., Scott, M.J., Loughran, P., Gibson, G., Sodhi, C., Watkins, S., Hackam, D., and Billiar, T.R. Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type-Specific Functions of TLR4 during Sepsis. Journal of Immunology, 190; 5152-60, 2013. PMID: 23562812
  48. Hackam, D.J., Good, M., & Sodhi, C.P. Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: Toll-like receptors throw the switch. Seminar in Pediatric Surgery. 22: 76-82, 2013 (Review).
  49. Yazji, I., Sodhi, C.P., Lee, E., Good, M., Egan, C., Afrazi, A., Neal, M.D., Jia, H., Lin, J., Ma, C., Branca, M.F., Prindle, T., Richardson, W.D., Ozolek, J., Billiar, T.R. Binion, D.G., Gladwin, M.T., & Hackam, D.J. Endothelial TLR4 Activation Impairs Intestinal Microcirculatory Perfusion in Necrotizing Enterocolitis via eNOS-NO-nitrite Signaling. Proceeding of National Academy of Sciences U S A.110: 9451-9456, 2013. PMID: 23650378
  50. Hackam, D.J., Afrazi, A., Good, M., & Sodhi, C.P. Innate immune signaling in the pathogenesis of necrotizing enterocolitis.Clinical & Developmental Immunology.475415, 10 pages, 2013 (Review). PMID: 23762089
  51. Neal, M.D., Jia, H., Eyer, B., Good, M., Guerriero, C.J., Sodhi, C.P., Afrazi, A., Prindle, T.J., Ma, C., Branca, M.F., Ozolek, J., Brodsky, J.L., Wipf, P., and Hackam, D.J. Discovery and Validation of a New Class of Small Molecule Toll Like Receptor 4 (TLR4) Inhibitors. PLoS One 2013 Jun 12;8(6): e65779. Print 2013. PMID: 23776545.
  52. Lu, P., Sodhi, C.P & Hackam, D.J. Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis. Pathophysiology. 2014 Feb; 21(1):81-93, PMID: 24365655.
  53. *Afrazi, A., *Branca M.F., *Sodhi, C.P, Good, M., Yamaguchi, Y., Egan, C.E., Lu, P., Jia, H., Shaffiey, S., Lin, J., Ma. C., Vincent, G., Prindle, T. Jr., Weyandt, S., Neal, M.D., Ozolek, J.A., Wiersch, J., Tschurtschenthaler, M., Shiota, C., Gittes, G.K., Billiar, T.R., Mollen, K.P., Kaser, A., Blumberg, R., & Hackam, D.J. Toll Like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis. Journal of Biological Chemistry, 2014 Feb 11; 289: 9584-9599, PMID: 24519940 * Equal first author.
  54. Bauer, E., Chanthaphavong, R.S, Sodhi, C.P., Hackam, D.J., Billiar, T.R., & Bauer, P.M. Genetic Deletion of TLR4 on Platelets Attenuates Experimental Pulmonary Hypertension. Circulation Research, 2014 May 9; 114(10): 1596-600, PMID: 24637196.
  55. Good, M., Sodhi, C.P., Ozolek, J.A., Buck, R.H., Goehring, K.C., Thomas, D.L., Vikram, A., Bibby, K., Morowitz, M.J., Firek, B., Lu, P., & Hackam, D.J. Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: evidence in mice for a role of TLR9. American Journal of Physiology Gastrointestinal Liver Physiology. 2014 Apr 17. 306 (11): G1021-G1032, PMID: 24742987.
  56. Lu, P., Sodhi, C.P., Jia, H., Shaffiey, S., Good, M., Branca, M.F., & Hackam, D.J. Animal Models of Necrotizing Enterocolitis : Pathophysiology, Translational Relevance and Challenges. American Journal of Physiology Gastrointestestinal Liver Physiology. 2014 Jun 1; 306(11): G917-28, PMID: 24763555.
  57. Good, M., Sodhi, C.P., & Hackam, D.J. Evidence-based feeding strategies before and after the development of necrotizing enterocolitis. Expert Rev Clin Immunol. 2014 July; 10 (7):875-84, PMID: 24898361.
  58. Ding, N., Chen, G., Hoffman, R., Loughran, P., Sodhi, C.P., Hackam, D.J., Billiar, T., & Neal.M. TLR4 Regulates Platelet Function and Contributes to Coagulation Abnormality and Organ Injury in Hemorrhagic Shock and Resuscitation. Circulation, Cardiovascular Genetics. 2014 July 21. pii: CIRCGENETICS.113.000398. [Epub ahead of print]).PMID: 25049041
  59. Brower-Sinning, R., Zhong, D., Good, M., Firek, B., Baker, R., Sodhi, C.P., Hackam, D.J., & Morowitz, M.J. Mucosa-associated bacterial diversity in necrotizing enterocolitis. PLoS One. 2014 Sep 9;9(9):e105046. doi: 10.1371/journal.pone.0105046. eCollection 2014. PMID: 25203729
  60. Wipf, P., Eyer, R. B., Yamaguchi, Y., Zhang, F., Neal, M.D., Sodhi, C.P., Good, M., Branca, M., Prindle. T., Lu. P., Brodsky, J.L., & Hackam, D.J. 1.      Synthesis of anti-inflammatory α-and β-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4). Tetrahedron Letters. 2015 in press.
  61. Buchholz, B.M., Shapiro, R.A., Vodovotz, Y., Billiar, T.R., Sodhi, C.P., Hackam, D.J., Bauer, A.J.. Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus. Am J Physiol Gastrointest Liver Physiol. 2015, In Press. PMID: 25747352.
  62. Sodhi, C.P., Hongpeng, J., Yamaguchi, Y., Lu, P., Good, M., Egan, C., Ozolek,J., Zhu, X., Billiar, T.R., & Hackam, D.J. Intestinal epithelial Toll-like Receptor-4 activation is required for the development of acute lung injury after trauma/hemorrhagic shock via the release of HMGB1 from the gut. Journal of Immunology, 2015.
  63. Good, M., Sodhi, C.P., Egan, C.E., Afrazi, E., Jia, H., Yamaguchi, Y., Lu, P., Branca, M., Ma, C., ., Prindle. T., Mielo, S., Pompa, A., Hodzic, Z., Ozolek, J.A., & Hackam, D.J. Breast milk protects against the development of necrotizing enterocolitis through inhibition of Toll Like Receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor. Mucosal Immunology, 2015.

Patents

NEAL, Matthew, D.; (US). SODHI, Chhinder, P.; (US). HACKAM,David, J. WIPF, Peter; (US).; U.S. Novel Tlr4 Inhibitors for the treatment of human infectious and inflammatory disorders.
Patent # 9,072,760 | 

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Memberships

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