Cheryl Stoddart, PhD
Professor Emeritus
My research has focused on the use of the SCID-hu Thy/Liv mouse model for preclinical evaluation of antiviral compounds and immunomodulating agents. The Thy/Liv model is constructed by implantation of organs supportive of human multilineage hematopoiesis and T-cell development (e.g., fetal liver and thymus) into the immunodeficient C.B-17 scid/scid mouse. Since 2000, I have been the Principal Investigator for a sole-sourced contract from NIH/NIAID, Tissue-Based Small Animal Model for HIV Drug Discovery funded to carry out these drug evaluations. The model has also been shown to be receptive to the surgical implantation of a number of other hematopoietic and nonhematopoietic human organ systems, including lymph node, small and large intestine, lung, skin, pituitary, ovary, and placenta. Mice with such implanted organs represent potential models that could be used to discover and evaluate stem cell populations normally resident within each of these organs.
Education
Publications
Stoddart CA, Curreli F, Horrigan S, Altieri A, Kurkin AV, Debnath AK. Comparative Pharmacokinetics of a Dual Inhibitor of HIV-1, NBD-14189, in Rats and Dogs with a Proof-of-Concept Evaluation of Antiviral Potency in SCID-hu Mouse Model. Viruses 2022. PMID: 36298823
Morvan MG, Teque F, Ye L, Moreno ME, Wang J, VandenBerg S, Stoddart CA, Kan YW, Levy JA. Genetically edited CD34+ cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells. Proceedings of the National Academy of Sciences of the United States of America 2021. PMID: 33975958
Cham LB, Torrez Dulgeroff LB, Tal MC, Adomati T, Li F, Bhat H, Huang A, Lang PA, Moreno ME, Rivera JM, Galkina SA, Kosikova G, Stoddart CA, McCune JM, Myers LM, Weissman IL, Lang KS, Hasenkrug KJ. Immunotherapeutic Blockade of CD47 Inhibitory Signaling Enhances Innate and Adaptive Immune Responses to Viral Infection. Cell reports 2020. PMID: 32294445
Maidji E, Moreno ME, Rivera JM, Joshi P, Galkina SA, Kosikova G, Somsouk M, Stoddart CA. Cellular HIV Reservoirs and Viral Rebound from the Lymphoid Compartments of 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine (EFdA)-Suppressed Humanized Mice. Viruses 2019. PMID: 30871222
Hogan LE, Vasquez J, Hobbs KS, Hanhauser E, Aguilar-Rodriguez B, Hussien R, Thanh C, Gibson EA, Carvidi AB, Smith LCB, Khan S, Trapecar M, Sanjabi S, Somsouk M, Stoddart CA, Kuritzkes DR, Deeks SG, Henrich TJ. Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30. PLoS pathogens 2018. PMID: 29470552
Vasquez JJ, Hussien R, Aguilar-Rodriguez B, Junger H, Dobi D, Henrich TJ, Thanh C, Gibson E, Hogan LE, McCune J, Hunt PW, Stoddart CA, Laszik ZG. Elucidating the Burden of HIV in Tissues Using Multiplexed Immunofluorescence and In Situ Hybridization: Methods for the Single-Cell Phenotypic Characterization of Cells Harboring HIV In Situ. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2018. PMID: 29462571
Rose R, Nolan DJ, Maidji E, Stoddart CA, Singer EJ, Lamers SL, McGrath MS. Eradication of HIV from Tissue Reservoirs: Challenges for the Cure. Volume 34 of Issue 1. AIDS research and human retroviruses 2017. PMID: 28691499
Maidji E, Somsouk M, Rivera JM, Hunt PW, Stoddart CA. Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction. Volume 13 of Issue 2. PLoS pathogens 2017. PMID: 28241080
Lamers SL, Rose R, Maidji E, Agsalda-Garcia M, Nolan DJ, Fogel GB, Salemi M, Garcia DL, Bracci P, Yong W, Commins D, Said J, Khanlou N, Hinkin CH, Sueiras MV, Mathisen G, Donovan S, Shiramizu B, Stoddart CA, McGrath MS, Singer EJ. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads. Volume 90 of Issue 20. Journal of virology 2016. PMID: 27466426
Rose R, Lamers SL, Nolan DJ, Maidji E, Faria NR, Pybus OG, Dollar JJ, Maruniak SA, McAvoy AC, Salemi M, Stoddart CA, Singer EJ, McGrath MS. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer. Volume 90 of Issue 20. Journal of virology 2016. PMID: 27466425
Joshi P, Maidji E, Stoddart CA. Inhibition of Heat Shock Protein 90 Prevents HIV Rebound. Volume 291 of Issue 19. The Journal of biological chemistry 2016. PMID: 26957545
Ghosn EE, Waters J, Phillips M, Yamamoto R, Long BR, Yang Y, Gerstein R, Stoddart CA, Nakauchi H, Herzenberg LA. Fetal Hematopoietic Stem Cell Transplantation Fails to Fully Regenerate the B-Lymphocyte Compartment. Volume 6 of Issue 1. Stem cell reports 2015. PMID: 26724903
Lamers SL, Rose R, Ndhlovu LC, Nolan DJ, Salemi M, Maidji E, Stoddart CA, McGrath MS. The meningeal lymphatic system: a route for HIV brain migration? Volume 22 of Issue 3. Journal of neurovirology 2015. PMID: 26572785
Stoddart CA, Galkina SA, Joshi P, Kosikova G, Moreno ME, Rivera JM, Sloan B, Reeve AB, Sarafianos SG, Murphey-Corb M, Parniak MA. Oral administration of the nucleoside EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine) provides rapid suppression of HIV viremia in humanized mice and favorable pharmacokinetic properties in mice and the rhesus macaque. Volume 59 of Issue 7. Antimicrobial agents and chemotherapy 2015. PMID: 25941222
Laing ST, Griffey SM, Moreno ME, Stoddart CA. CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice. Journal of comparative pathology 2015. PMID: 25670669
Stoddart CA, Galkina SA, Joshi P, Kosikova G, Long BR, Maidji E, Moreno ME, Rivera JM, Sanford UR, Sloan B, Cieplak W, Wrin T, Chan-Hui PY. Efficacy of broadly neutralizing monoclonal antibody PG16 in HIV-infected humanized mice. Volume 462-463. Virology 2014. PMID: 24971704
Joshi P, Sloan B, Torbett BE, Stoddart CA. Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Volume 436 of Issue 1. Virology 2012. PMID: 23200770
Maidji E, Kosikova G, Joshi P, Stoddart CA. Impaired surfactant production by alveolar epithelial cells in a SCID-hu lung mouse model of congenital human cytomegalovirus infection. Volume 86 of Issue 23. Journal of virology 2012. PMID: 22973041
Long BR, Stoddart CA. OMIP-012: Phenotypic and numeric determination of human leukocyte reconstitution in humanized mice. Volume 81 of Issue 8. Cytometry. Part A : the journal of the International Society for Analytical Cytology 2012. PMID: 22653780
Stoddart CA, Nault G, Galkina SA, Bousquet-Gagnon N, Bridon D, Quraishi O. Preexposure prophylaxis with albumin-conjugated C34 peptide HIV-1 fusion inhibitor in SCID-hu Thy/Liv mice. Volume 56 of Issue 4. Antimicrobial agents and chemotherapy 2012. PMID: 22252805
Long BR, Stoddart CA. Alpha interferon and HIV infection cause activation of human T cells in NSG-BLT mice. Volume 86 of Issue 6. Journal of virology 2012. PMID: 22238321
Vyas GN, Stoddart CA, Killian MS, Brennan TV, Goldberg T, Ziman A, Bryson Y. Derivation of non-infectious envelope proteins from virions isolated from plasma negative for HIV antibodies. Volume 40 of Issue 1. Biologicals : journal of the International Association of Biological Standardization 2011. PMID: 22192456
Baum PD, Sullam PM, Stoddart CA, McCune JM. Abacavir increases platelet reactivity via competitive inhibition of soluble guanylyl cyclase. Volume 25 of Issue 18. AIDS (London, England) 2011. PMID: 21941165
Stoddart CA, Maidji E, Galkina SA, Kosikova G, Rivera JM, Moreno ME, Sloan B, Joshi P, Long BR. Superior human leukocyte reconstitution and susceptibility to vaginal HIV transmission in humanized NOD-scid IL-2R?(-/-) (NSG) BLT mice. Volume 417 of Issue 1. Virology 2011. PMID: 21684569
Joshi P, Stoddart CA. Impaired infectivity of ritonavir-resistant HIV is rescued by heat shock protein 90AB1. Volume 286 of Issue 28. The Journal of biological chemistry 2011. PMID: 21602280
Jeffrey Mold, Shivkumar Venkatasubrahmanyam, Trevor Burt, Jakob Michaelsson, Kenneth Weinberg, Douglas Nixon, Cheryl Stoddart, Joseph McCune. How we achieve tolerance for our mothers: evidence for a layered immune system in humans (64.1). The Journal of Immunology 2011. PMID:
Favre D, Stoddart CA, Emu B, Hoh R, Martin JN, Hecht FM, Deeks SG, McCune JM. HIV disease progression correlates with the generation of dysfunctional naive CD8(low) T cells. Volume 117 of Issue 7. Blood 2011. PMID: 21200021
Mold JE, Venkatasubrahmanyam S, Burt TD, Michaëlsson J, Rivera JM, Galkina SA, Weinberg K, Stoddart CA, McCune JM. Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans. Volume 330 of Issue 6011. Science (New York, N.Y.) 2010. PMID: 21164017
Stoddart CA, Keir ME, McCune JM. IFN-alpha-induced upregulation of CCR5 leads to expanded HIV tropism in vivo. Volume 6 of Issue 2. PLoS pathogens 2010. PMID: 20174557
Stoddart CA, Nault G, Galkina SA, Thibaudeau K, Bakis P, Bousquet-Gagnon N, Robitaille M, Bellomo M, Paradis V, Liscourt P, Lobach A, Rivard ME, Ptak RG, Mankowski MK, Bridon D, Quraishi O. Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. Volume 283 of Issue 49. The Journal of biological chemistry 2008. PMID: 18809675
Stoddart CA, Joshi P, Sloan B, Bare JC, Smith PC, Allaway GP, Wild CT, Martin DE. Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Volume 2 of Issue 11. PloS one 2007. PMID: 18043758
Stoddart CA, Bales CA, Bare JC, Chkhenkeli G, Galkina SA, Kinkade AN, Moreno ME, Rivera JM, Ronquillo RE, Sloan B, Black PL. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals. Volume 2 of Issue 7. PloS one 2007. PMID: 17668043
Chen JL, Kernan MR, Jolad SD, Stoddart CA, Bogan M, Cooper R. Dysoxylins A-D, tetranortriterpenoids with potent anti-RSV activity from Dysoxylum gaudichaudianum. Volume 70 of Issue 2. Journal of natural products 2007. PMID: 17315968
Red-Horse K, Rivera J, Schanz A, Zhou Y, Winn V, Kapidzic M, Maltepe E, Okazaki K, Kochman R, Vo KC, Giudice L, Erlebacher A, McCune JM, Stoddart CA, Fisher SJ. Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation. Volume 116 of Issue 10. The Journal of clinical investigation 2006. PMID: 16998586
. Models of HIV-1 disease: A review of current status. 2006. PMID:
Richard A Reyes, Cheryl Stoddart. Suppression of lymphocyte egress in simian immunodeficiency virus-infected rhesus macaques. 2006. PMID:
Red-Horse K, Rivera J, Schanz A, Zhou Y, Winn V, Kapidzic M, Maltepe E, Okazaki K, Kochman R, Vo KC, Giudice L, Erlebacher A, McCune JM, Stoddart CA, Fisher SJ. Literature watch. Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation. Lymphatic research and biology 2006. PMID: 17394406
Chatterji U, Bobardt MD, Stanfield R, Ptak RG, Pallansch LA, Ward PA, Jones MJ, Stoddart CA, Scalfaro P, Dumont JM, Besseghir K, Rosenwirth B, Gallay PA. Naturally occurring capsid substitutions render HIV-1 cyclophilin A independent in human cells and TRIM-cyclophilin-resistant in Owl monkey cells. Volume 280 of Issue 48. The Journal of biological chemistry 2005. PMID: 16199531
Brilot F, Geenen V, Hober D, Stoddart CA. Coxsackievirus B4 infection of human fetal thymus cells. Volume 78 of Issue 18. Journal of virology 2004. PMID: 15331720
Sandberg JK, Stoddart CA, Brilot F, Jordan KA, Nixon DF. Development of innate CD4+ alpha-chain variable gene segment 24 (Valpha24) natural killer T cells in the early human fetal thymus is regulated by IL-7. Volume 101 of Issue 18. Proceedings of the National Academy of Sciences of the United States of America 2004. PMID: 15118099
Napolitano LA, Stoddart CA, Hanley MB, Wieder E, McCune JM. Effects of IL-7 on early human thymocyte progenitor cells in vitro and in SCID-hu Thy/Liv mice. Volume 171 of Issue 2. Journal of immunology (Baltimore, Md. : 1950) 2003. PMID: 12847229
Stoddart CA, Geleziunas R, Ferrell S, Linquist-Stepps V, Moreno ME, Bare C, Xu W, Yonemoto W, Bresnahan PA, McCune JM, Greene WC. Human immunodeficiency virus type 1 Nef-mediated downregulation of CD4 correlates with Nef enhancement of viral pathogenesis. Volume 77 of Issue 3. Journal of virology 2003. PMID: 12525647
Keir ME, Rosenberg MG, Sandberg JK, Jordan KA, Wiznia A, Nixon DF, Stoddart CA, McCune JM. Generation of CD3+CD8low thymocytes in the HIV type 1-infected thymus. Journal of immunology (Baltimore, Md. : 1950) 2002. PMID: 12193754
Keir ME, Stoddart CA, Linquist-Stepps V, Moreno ME, McCune JM. IFN-alpha secretion by type 2 predendritic cells up-regulates MHC class I in the HIV-1-infected thymus. Volume 168 of Issue 1. Journal of immunology (Baltimore, Md. : 1950) 2002. PMID: 11751977
Strizki JM, Xu S, Wagner NE, Wojcik L, Liu J, Hou Y, Endres M, Palani A, Shapiro S, Clader JW, Greenlee WJ, Tagat JR, McCombie S, Cox K, Fawzi AB, Chou CC, Pugliese-Sivo C, Davies L, Moreno ME, Ho DD, Trkola A, Stoddart CA, Moore JP, Reyes GR, Baroudy BM. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America 2001. PMID: 11606733
Stoddart CA, Liegler TJ, Mammano F, Linquist-Stepps VD, Hayden MS, Deeks SG, Grant RM, Clavel F, McCune JM. Impaired replication of protease inhibitor-resistant HIV-1 in human thymus. Nature medicine 2001. PMID: 11385509
Gobbi A, Stoddart CA, Locatelli G, Santoro F, Bare C, Linquist-Stepps V, Moreno ME, Abbey NW, Herndier BG, Malnati MS, McCune JM, Lusso P. Coinfection of SCID-hu Thy/Liv mice with human herpesvirus 6 and human immunodeficiency virus type 1. Journal of virology 2000. PMID: 10954574
Stoddart CA, Moreno ME, Linquist-Stepps VD, Bare C, Bogan MR, Gobbi A, Buckheit RW, Bedard J, Rando RF, McCune JM. Antiviral activity of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652) against lamivudine-resistant human immunodeficiency virus type 1 in SCID-hu Thy/Liv mice. Antimicrobial agents and chemotherapy 2000. PMID: 10681360
Dittmer D, Stoddart C, Renne R, Linquist-Stepps V, Moreno ME, Bare C, McCune JM, Ganem D. Experimental transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) to SCID-hu Thy/Liv mice. The Journal of experimental medicine 1999. PMID: 10601360
Berkowitz RD, van't Wout AB, Kootstra NA, Moreno ME, Linquist-Stepps VD, Bare C, Stoddart CA, Schuitemaker H, McCune JM. R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus. Journal of virology 1999. PMID: 10438873
Gobbi A, Stoddart CA, Malnati MS, Locatelli G, Santoro F, Abbey NW, Bare C, Linquist-Stepps V, Moreno MB, Herndier BG, Lusso P, McCune JM. Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID-hu Thy/Liv mice. The Journal of experimental medicine 1999. PMID: 10377191
Berkowitz RD, Alexander S, Bare C, Linquist-Stepps V, Bogan M, Moreno ME, Gibson L, Wieder ED, Kosek J, Stoddart CA, McCune JM. CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo. Journal of virology 1998. PMID: 9811751
Chen JL, Blanc P, Stoddart CA, Bogan M, Rozhon EJ, Parkinson N, Ye Z, Cooper R, Balick M, Nanakorn W, Kernan MR. New iridoids from the medicinal plant Barleria prionitis with potent activity against respiratory syncytial virus. Journal of natural products 1998. PMID: 9784173
Stoddart CA, Rabin L, Hincenbergs M, Moreno M, Linquist-Stepps V, Leeds JM, Truong LA, Wyatt JR, Ecker DJ, McCune JM. Inhibition of human immunodeficiency virus type 1 infection in SCID-hu Thy/Liv mice by the G-quartet-forming oligonucleotide, ISIS 5320. Antimicrobial agents and chemotherapy 1998. PMID: 9687417
Kernan MR, Amarquaye A, Chen JL, Chan J, Sesin DF, Parkinson N, Ye Z, Barrett M, Bales C, Stoddart CA, Sloan B, Blanc P, Limbach C, Mrisho S, Rozhon EJ. Antiviral phenylpropanoid glycosides from the medicinal plant Markhamia lutea. Journal of natural products 1998. PMID: 9599250
Linquist V, Stoddart CA, McCune JM. UV irradiation of polystyrene pipets releases PCR inhibitors. BioTechniques 1998. PMID: 9454951
Kernan MR, Sendl A, Chen JL, Jolad SD, Blanc P, Murphy JT, Stoddart CA, Nanakorn W, Balick MJ, Rozhon EJ. Two new lignans with activity against influenza virus from the medicinal plant Rhinacanthus nasutus. Journal of natural products 1997. PMID: 9214738
Sendl A, Chen JL, Jolad SD, Stoddart C, Rozhon E, Kernan M, Nanakorn W, Balick M. Two new naphthoquinones with antiviral activity from Rhinacanthus nasutus. Journal of natural products 1996. PMID: 8792629
Cardin RD, Abenes GB, Stoddart CA, Mocarski ES. Murine cytomegalovirus IE2, an activator of gene expression, is dispensable for growth and latency in mice. Virology 1995. PMID: 7747475
Stoddart CA, Cardin RD, Boname JM, Manning WC, Abenes GB, Mocarski ES. Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus. Journal of virology 1994. PMID: 8083964
Ubillas R, Jolad SD, Bruening RC, Kernan MR, King SR, Sesin DF, Barrett M, Stoddart CA, Flaster T, Kuo J, Ayala F, Meza E, Castañel M, McMeekin D, Rozhon E, Tempesta MS, Barnard D, Huffman J, Smee D, Sidwell R, Soike K, Brazier A, Safrin S, Orlando R, Kenny PT, Berova N, Nakanishi K. SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago). Phytomedicine : international journal of phytotherapy and phytopharmacology 1994. PMID: 23195881
Manning WC, Stoddart CA, Lagenaur LA, Abenes GB, Mocarski ES. Cytomegalovirus determinant of replication in salivary glands. Journal of virology 1992. PMID: 1316482
Stoddart CA, Scott FW. Intrinsic resistance of feline peritoneal macrophages to coronavirus infection correlates with in vivo virulence. Journal of virology 1989. PMID: 2521188