Steven L. Zeichner

Education

  • BA, The University of Chicago, Chicago, IL
  • MD, The University of Chicago, Chicago, IL
  • PhD, The University of Chicago, Chicago, IL
  • Intern/ Resident, Children's Hospital of Philadelphia
  • Fellowship, Children's Hospital of Philadelphia

Primary Appointment

  • Professor, Pediatrics

Contact

Research Interest(s)

Pathogenesis of infectious diseases and the development of new therapies and vaccines for infectious diseases and cancers.

Research Description

We study infectious disease pathogenesis and work to develop new therapies and diagnostics for infectious diseases and cancers using the new insights that we develop. In one set of projects we are working to turn the gastrointestinal (GI) immune system of a mouse into a technology called Intestinal Selection of Immunogenic Antigens (ISIA) that can distinguish highly immunogenic antigens from less immunogenic antigens. The technology employs a combination of synthetic biology, new insights into the microbiome, the notion of DNA barcoding, and Gram-negative autotransporters to interrogate, without any advance assumptions or biases, the entire, intact GI immune system of a mouse. In ISIA, we synthesize a set of plasmids, each of which carries a unique DNA barcode and places a test protein on the surface of bacteria capable of long-term colonization of the GI tract using a Gram-negative autotransporter. We inoculate mice with bacteria transformed with the set of barcoded plasmids expressing the different test proteins, and then assay for the abundance of the different barcodes in the feces of mice. If the GI immune system of the mice identifies a surface test protein as being particularly immunogenic it will, in a Darwinian sense, "select against" the bacteria expressing the immunogenic antigen and eliminate it from the GI tract. We detect elimination from the GI tract using assays for the DNA barcodes. The technology has applications in the development of new vaccines for infectious diseases and therapeutic cancer vaccines, and for working to make biologics, such as therapeutic proteins, minimally antigenic. In this context, we are actively working on developing new prophylactic vaccines for HIV and therapeutic cancer vaccines. In other projects, we seek to understand the control of Human Immunodeficiency Virus and herpesvirus latency. We have recently shown that Kaposi’s Sarcoma-associated Herpesvirus (KSHV) and other herpesviruses, and HIV can sense the health of their host cells. When the viruses sense that their host cells are about to undergo apoptosis, they respond by starting to replicate. If the viruses were not able to reproduce before the host cell died an apoptotic death, then the viruses would be unable to produce progeny, so presumably there is a strong evolutionary imperative for viruses to evolve ways to sense and respond to impending host cell apoptosis. These studies have implications for attempts at curing HIV and for understanding some of the complications that accompany cytotoxic exposures like cancer chemotherapy and bone marrow transplantation. We also are working on more clinically oriented projects related to infectious disease pathogenesis. For example, we recently showed that the community of microbes present in the appendix of appendicitis patients differed from the community of microbes present in the appendix of patients without appendicitis, that the microbes present in the appendix differed from the microbes present in the rectum, and perhaps most interestingly, that the microbes present in the rectum of patients with appendicitis differed from the microbes present in the rectum of patients who did not have appendicitis. This finding suggested that it might be possible to design a diagnostic test for appendicitis based on identifying and quantitating the microbes in the rectum of patients who might possibly have appendicitis. This would be helpful because such a microbe-base test would be less expensive, faster, easier, and safer than the current methods used to diagnose appendicitis, such as CT scan, which administers significant doses of radiation. We are currently conducting a larger prospective study to try to confirm whether there might be a distinctive community of microbes in the rectum of patients that could be used to diagnose appendicitis.

Selected Publications

  • Goldberg B, Mongodin E, Jones C, Chung M, Fraser C, Tate A, Zeichner S. The Oral Bacterial Communities of Children with Well-Controlled HIV Infection and without HIV Infection. PloS one. 2015;10(7): e0131615. PMID: 26146997 | PMCID: PMC4492946
  • Khan S, Hand N, Zeichner S. Apoptosis-induced activation of HIV-1 in latently infected cell lines. Retrovirology. 2015;12 42. PMID: 25980942 | PMCID: PMC4469242
  • Jackson H, Mongodin E, Davenport K, Fraser C, Sandler A, Zeichner S. Culture-independent evaluation of the appendix and rectum microbiomes in children with and without appendicitis. PloS one. 2014;9(4): e95414. PMID: 24759879 | PMCID: PMC3997405
  • Fernandez G, Zaikos T, Khan S, Jacobi A, Behlke M, Zeichner S. Targeting IκB proteins for HIV latency activation: the role of individual IκB and NF-κB proteins. Journal of virology. 2013;87(7): 3966-78. PMID: 23365428 | PMCID: PMC3624191
  • Prasad A, Remick J, Zeichner S. Activation of human herpesvirus replication by apoptosis. Journal of virology. 2013;87(19): 10641-50. PMID: 23885073 | PMCID: PMC3807386
  • Prasad A, Lu M, Lukac D, Zeichner S. An alternative Kaposi's sarcoma-associated herpesvirus replication program triggered by host cell apoptosis. Journal of virology. 2012;86(8): 4404-19. PMID: 22345480 | PMCID: PMC3318647
  • Ravel J, Gajer P, Fu L, Mauck C, Koenig S, Sakamoto J, Motsinger-Reif A, Doncel G, Zeichner S. Twice-daily application of HIV microbicides alter the vaginal microbiota. mBio. 2012;3(6). PMID: 23249810 | PMCID: PMC3529542
  • Fernandez G, Zeichner S. Cell line-dependent variability in HIV activation employing DNMT inhibitors. Virology journal. 2010;7 266. PMID: 20942961 | PMCID: PMC2964676
  • Cherrier T, Suzanne S, Redel L, Calao M, Marban C, Samah B, Mukerjee R, Schwartz C, Gras G, Sawaya B, Zeichner S, Aunis D, Van Lint C, Rohr O. p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1. Oncogene. 2009;28(38): 3380-9. PMID: 19581932 | PMCID: PMC3438893
  • Harada S, Hazra R, Tamiya S, Zeichner S, Mitsuya H. Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. Antiviral research. 2007;75(2): 159-66. PMID: 17418430
  • Harada S, Hazra R, Tamiya S, Zeichner S, Mitsuya H. Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. Antiviral research. 2007;75(2): 159-66. PMID: 17418430
  • Gafni R, Hazra R, Reynolds J, Maldarelli F, Tullio A, DeCarlo E, Worrell C, Flaherty J, Yale K, Kearney B, Zeichner S. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics. 2006;118(3): e711-8. PMID: 16923923
  • Martin S, Wolters P, Toledo-Tamula M, Zeichner S, Hazra R, Civitello L. Cognitive functioning in school-aged children with vertically acquired HIV infection being treated with highly active antiretroviral therapy (HAART). Developmental neuropsychology. 2006;30(2): 633-57. PMID: 16995830
  • Hazra R, Gafni R, Maldarelli F, Balis F, Tullio A, DeCarlo E, Worrell C, Steinberg S, Flaherty J, Yale K, Kearney B, Zeichner S. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005;116(6): e846-54. PMID: 16291735
  • Yoshizuka N, Yoshizuka-Chadani Y, Krishnan V, Zeichner S. Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway. Journal of virology. 2005;79(17): 11366-81. PMID: 16103188 | PMCID: PMC1193619
  • Krishnan V, Zeichner S. Alterations in the expression of DEAD-box and other RNA binding proteins during HIV-1 replication. Retrovirology. 2004;1 42. PMID: 15588285 | PMCID: PMC543576
  • Krishnan V, Zeichner S. Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency. Journal of virology. 2004;78(17): 9458-73. PMID: 15308739 | PMCID: PMC506933
  • Lu M, Suen J, Frias C, Pfeiffer R, Tsai M, Chuang E, Zeichner S. Dissection of the Kaposi's sarcoma-associated herpesvirus gene expression program by using the viral DNA replication inhibitor cidofovir. Journal of virology. 2004;78(24): 13637-52. PMID: 15564474 | PMCID: PMC533899
  • Hazra R, Balis F, Tullio A, DeCarlo E, Worrell C, Steinberg S, Flaherty J, Yale K, Poblenz M, Kearney B, Zhong L, Coakley D, Blanche S, Bresson J, Zuckerman J, Zeichner S. Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children. Antimicrobial agents and chemotherapy. 2003;48(1): 124-9. PMID: 14693529 | PMCID: PMC310184
  • Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner S, Jung J. Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. Journal of virology. 2003;77(7): 4205-20. PMID: 12634378 | PMCID: PMC150665
  • Zhang P, Ng P, Caridha D, Leach R, Asher L, Novak M, Smith W, Zeichner S, Chiang P. Gene expressions in Jurkat cells poisoned by a sulphur mustard vesicant and the induction of apoptosis. British journal of pharmacology. 2002;137(2): 245-52. PMID: 12208782 | PMCID: PMC1573481
  • Jankelevich S, Mueller B, Mackall C, Smith S, Zwerski S, Wood L, Zeichner S, Serchuck L, Steinberg S, Nelson R, Sleasman J, Nguyen B, Pizzo P, Yarchoan R. Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine. The Journal of infectious diseases. 2001;183(7): 1116-20. PMID: 11237839
  • Ng P, Iha H, Iwanaga Y, Bittner M, Chen Y, Jiang Y, Gooden G, Trent J, Meltzer P, Jeang K, Zeichner S. Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappaB activation. Oncogene. 2001;20(33): 4484-96. PMID: 11494144
  • Robinson M, Fine H, Ross M, Mont E, Bryant-Greenwood P, Hertle R, Tisdale J, Young N, Zeichner S, Van Waes C, Whitcup S, Walsh T. Sino-orbital-cerebral aspergillosis in immunocompromised pediatric patients. The Pediatric infectious disease journal. 2001;19(12): 1197-203. PMID: 11144384
  • Robinson M, Salit R, Bryant-Greenwood P, Zeichner S, Wood L, Jaffe E, van Waes C, Magrath I. Burkitt's/Burkitt's-like lymphoma presenting as bacterial sinusitis in two HIV-infected children. AIDS patient care and STDs. 2001;15(9): 453-8. PMID: 11587630
  • Feng Y, Biggar R, Gee D, Norwood D, Zeichner S, Dimitrov D. Long-term telomere dynamics: modest increase of cell turnover in HIV-infected individuals followed for up to 14 years. Pathobiology : journal of immunopathology, molecular and cellular biology. 1999;67(1): 34-8. PMID: 9873226
  • Feng Y, Norwood D, Shibata R, Gee D, Xiao X, Martin M, Zeichner S, Dimitrov D. Telomere dynamics in HIV-1 infected and uninfected chimpanzees measured by an improved method based on high-resolution two-dimensional calibration of DNA sizes. Journal of medical primatology. 1999;27(5): 258-65. PMID: 9926982
  • Shibata R, Feng Y, Gee D, Norwood D, Xiao X, Zeichner S, Martin M, Dimitrov D. Telomere dynamics in monkeys: increased cell turnover in macaques infected with chimeric simian-human immunodeficiency viruses. Journal of medical primatology. 1999;28(1): 1-10. PMID: 10372535
  • Zeichner S, Palumbo P, Feng Y, Xiao X, Gee D, Sleasman J, Goodenow M, Biggar R, Dimitrov D. Rapid telomere shortening in children. Blood. 1999;93(9): 2824-30. PMID: 10216076
  • Foscarnet. Pediatrics in review / American Academy of Pediatrics. 1998;19(12): 399-400. PMID: 9849068
  • Tetracycline update. Pediatrics in review / American Academy of Pediatrics. 1998;19(1): 32. PMID: 9439167
  • Maldarelli F, Xiang C, Chamoun G, Zeichner S. The expression of the essential nuclear splicing factor SC35 is altered by human immunodeficiency virus infection. Virus research. 1998;53(1): 39-51. PMID: 9617768
  • Mueller B, Zeichner S, Kuznetsov V, Heath-Chiozzi M, Pizzo P, Dimitrov D. Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy. AIDS (London, England). 1998;12(15): F191-6. PMID: 9814861
  • Ensoli F, Wang H, Fiorelli V, Zeichner S, De Cristofaro M, Luzi G, Thiele C. HIV-1 infection and the developing nervous system: lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors. Journal of neurovirology. 1997;3(4): 290-8. PMID: 9291237
  • Kedar P, Arden K, Foyle M, Pope J, Zeichner S. Umbilical Cord Blood Mononuclear Cell HIV-1 LTR Binding Activities. Journal of biomedical science. 1997;4(5): 217-228. PMID: 12386383
  • Sorbara L, Maldarelli F, Chamoun G, Schilling B, Chokekijcahi S, Staudt L, Mitsuya H, Simpson I, Zeichner S. Human immunodeficiency virus type 1 infection of H9 cells induces increased glucose transporter expression. Journal of virology. 1996;70(10): 7275-9. PMID: 8794382 | PMCID: PMC190788
  • Zeichner S, Mueller B, Pizzo P, Dimitrov D. Kinetics of HIV-1 RNA concentration changes in pediatric patients. Pathobiology : journal of immunopathology, molecular and cellular biology. 1996;64(6): 289-94. PMID: 9159022
  • The molecular biology of HIV. Insights into pathogenesis and targets for therapy. Clinics in perinatology. 1994;21(1): 39-73. PMID: 8013186
  • Kim J, Gonzalez-Scarano F, Zeichner S, Alwine J. Replication of type 1 human immunodeficiency viruses containing linker substitution mutations in the -201 to -130 region of the long terminal repeat. Journal of virology. 1993;67(3): 1658-62. PMID: 8437235 | PMCID: PMC237538
  • Zeichner S, Hirka G, Andrews P, Alwine J. Differentiation-dependent human immunodeficiency virus long terminal repeat regulatory elements active in human teratocarcinoma cells. Journal of virology. 1992;66(4): 2268-73. PMID: 1548760 | PMCID: PMC289020
  • Zeichner S, Kim J, Alwine J. Analysis of the human immunodeficiency virus long terminal repeat by in vitro transcription competition and linker scanning mutagenesis. Gene expression. 1991;1(1): 15-27. PMID: 1820204
  • Zeichner S, Kim J, Alwine J. Linker-scanning mutational analysis of the transcriptional activity of the human immunodeficiency virus type 1 long terminal repeat. Journal of virology. 1991;65(5): 2436-44. PMID: 2016766 | PMCID: PMC240597
  • Zeichner S, Plotkin S. Mechanisms and pathways of congenital infections. Clinics in perinatology. 1988;15(2): 163-88. PMID: 3288420
  • Isolation and characterization of macrophage phagosomes containing infectious and heat-inactivated Chlamydia psittaci: two phagosomes with different intracellular behaviors. Infection and immunity. 1983;40(3): 956-66. PMID: 6852926 | PMCID: PMC348145
  • Isolation and characterization of phagosomes containing Chlamydia psittaci from L cells. Infection and immunity. 1982;38(1): 325-42. PMID: 7141694 | PMCID: PMC347735
  • Moulder J, Zeichner S, Levy N. Association between resistance to superinfection and patterns of surface protein labeling in mouse fibroblasts (L cells) persistently infected with Chlamydia psittaci. Infection and immunity. 1982;35(3): 834-9. PMID: 7068218 | PMCID: PMC351123
  • Moulder J, Levy N, Zeichner S, Lee C. Attachment defect in mouse fibroblasts (L cells) persistently infected with Chlamydia psittaci. Infection and immunity. 1981;34(1): 285-91. PMID: 7298188 | PMCID: PMC350854