Areas of research interest

The research focus in our laboratory is to formulate innovative gene and cell therapeutic approaches for the treatment of hemophiliacs. There are three major areas that we are working on.

Gene therapy of hemophilia A

Hemophilia A is a recessive X-linked bleeding disorder resulting from a FVIII deficiency. Although protein replacement therapy is effective for hemophilia A treatment, up to 35% of patients may develop inhibitory antibodies (referred to as inhibitors) that neutralize FVIII activity. Introducing FVIII expression via genetic therapy is an attractive alternative treatment for hemophilia A patients. However, the potential to develop inhibitors to the transgene protein remains a significant concern. We have recently developed a novel gene therapy approach in which FVIII is targeted and stored in platelet ɑ-granules. Using a transgenic mouse model, we showed that FVIII can be specifically expressed and stored together with its carrier protein, VWF, in platelet ɑ-granules when it is driven by the platelet-specific ɑIIb promoter (2bF8) and that platelet-FVIII can correct the murine hemophilia A phenotype even in the presence of high-titer inhibitors. To apply this gene therapy to a clinically translatable protocol, we use lentiviral gene delivery to hematopoietic stem cells (HSCs) to introduce FVIII expression in platelets. We found that 2bF8 lentiviral gene delivery to HSCs can not only restore hemostasis, but also induce antigen-specific immune tolerance in hemophilia A mice. Our current work aims to 1) further optimize this approach; 2) dissect the potential underlying mechanisms by which immune tolerance is induced after platelet gene therapy; and 3) translate findings made in laboratory animals to human patients.

Gene therapy of hemophilia B

Hemophilia B is a genetic bleeding disorder which results from a FIX deficiency. Although the incidence of anti-FIX inhibitor development is lower (5%) in hemophilia B patients after protein replacement therapy, anaphylaxis is a daunting problem in inhibitor patients, which limits the use of FIX infusion and increases the risk of morbidity and mortality. Our studies show that FIX can be ectopically expressed and stored in platelet ɑ-granules when it is driven under the same ɑIIb promoter that we use for platelet-FVIII expression. Platelet-derived FIX, which is fully γ-carboxylated, can rescue bleeding diathesis in hemophilia B mice, but the clinical efficacy is limited in the presence of anti-FIX inhibitors. Although platelet-FIX does not maintain clinical efficacy in the face of inhibitors, targeting FIX expression to platelets is still an attractive potential strategy for gene therapy of hemophilia B. Indeed, our studies demonstrate that 2bF9 gene delivery to HSCs not only restores hemostasis, but also induce FIX-specific immune tolerance in hemophilia B mice. Our current work aims to optimize the FIX expression and develop a protocol for gene therapy of hemophilia B with pre-existing immunity.

FVIII immune responses in hemophilia A

The development of inhibitors against FVIII is not only a significant complication in protein replacement therapy but also a hurdle in gene therapy of hemophilia A. Understanding how FVIII immune responses occur may open a new therapeutic approach to limiting immune responses. Currently, we are dissecting the functional properties of recently identified subsets of immune cells, including T follicular help (Tfh) cells and T follicular help regulatory (Tfr) cells in FVIII immune responses. This will help us to better understand the cellular and molecular mechanisms of FVIII inhibitor development and assist us to identify potential novel target(s) for therapeutic intervention to prevent or reverse FVIII inhibitor development. In addition, we want to know how VWF impacts FVIII immune responses in hemophilia A. Our studies demonstrate that VWF is essential for maintaining platelet-FVIII efficacy in hemophilia A with inhibitors. VWF reduces inhibitor inactivation of FVIII, exerting a protective effect both in vitro and in vivo. VWF/FVIII association plus the apparent ability of VWF to delay the time-dependent inactivation of FVIII by inhibitors provides mechanisms by which platelet-derived FVIII maintains function even in the presence of inhibitors when FVIII is targeted to platelets for gene therapy of hemophilia A with inhibitors. Our current work aims to investigate the roles of VWF in FVIII immunity in hemophilia A.

Grants

• R01 HL 102035, "Platelet-derived FVIII gene theraphy of hemophilia A", Role: PI (2010-2028)
• R01 HL 142791, "A phase I clinical trial testing Feasibility of hematopoietic stem cell gene therapy using platelet FVIII to safely improve hemostasis for severe hemophilia A with inihibitory antibodies to FVIII," Role: Co-I (2019-2025)
• R01 HL166382, “Understanding and Controlling the Contribution of Fibrinolysis to Bleeding Using a Long-Acting Antifibrinolytic RNA Therapy”, Role: Co-I (2023-2027)
• MACC FUND, "FVIII immune responses in hemophilia A", Role: PI
• Joan Cox Gill CCBD/MSI Clinical & Translational Pilot Award, "Evaluating T follicular helper cells in FVIII inhibitor development and ITI in patients with Hemophilia A", Role: PI (2021-2024)

Jocelyn Schroeder
Research Technologist III

Saurabh Kumar, PhD
Postdoctoral Fellow

Hongyin Yu
IDP Graduate Student

Mikayla Ettmayer
Animal Technician

Dr. Qizhen Shi, M.D., Ph.D. has many published papers including:

Publications

Dr. Qizhen Shi, M.D., Ph.D. has many published papers including:

• Strilchuk AW, Hur WS, Batty P, Sang Y, Abrahams SR, Yong ASM, Leung J, Silva LM, Schroeder JA, Nesbitt K, de Laat B, Moutsopoulos NM, Bugge TH, Shi Q, Cullis PR, Merricks EP, Wolberg AS, Flick MJ, Lillicrap D, Nichols TC, Kastrup CJ. Lipid nanoparticles and RNAi targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A. Sci Transl Med 2024 Feb 21; 16(735):eadh0027. Doi:10.1126/scitranslmed.adh0027. Epub 2024 Feb 21. PubMed PMID: 38381848; NIHMSID:NIHMS2006195.
• Kumar S, Schroeder JA, and Shi Q. Platelet-targeted gene therapy induces immune tolerance in hemophilia and beyond. J Thromb Haemost 2024 Jan;22(1):23-34. doi: 10.1016/j.jtha.2023.07.025. Epub 2023 Aug 7. Review. PubMed PMID: 37558132; PubMed Central PMCID: PMC11249137.
• Biswas R, Boyd E, Steenackers A, Schulte ML, Eaton N, Reusswig F, Yu H, Shi Q, Plomann M, Hoffmeister KM, and Falet H. Mice lacking PACSIN2 display severe thrombus formation defects due to hyperactive platelet integrin β1. J Thromb Haemost 2023 Dec; 21(12):3619-3632. doi: 10.1016/j.jtha.2023.08.026.
• Li J, Karakas D, Xue F, Chen Y, Zhu G, Yucel YH, MacParland SA, Zhang H, Semple JW, Freedman J, Shi Q* and Ni H.* Desialylated platelet clearance in the liver is a novel mechanism of systemic immunosuppression. SJP Research 2023 Oct 5;6:0236. doi: 10.34133/research.0236. *Corresponding author. PMCID: PMC10551749. Featured Article: “In This Issue”. Chen L & Morell CN “Commentary on “Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells” doi.org/10.34133/research.0279.
• Jing W, Baumgartner CK, Xue F, Schroeder JA, and Shi Q. Pre-existing anti-FVIII immunity alters therapeutic platelet-targeted FVIII engraftment in the system preconditioned with busulfan alone through cytotoxic CD8 T cells. J Thromb Haemost 2023; Mar 1; 21(3):488-498. doi.org/10.1016/j.jtha.2022.10.006. PMID: 36696197.
• Luo L, Zheng Q, Chen Z, Huang M, Fu L, Hu J, Shi Q, and Chen Y. Hemophilia A patients with inhibitors: mechanistic insights and novel therapeutic implications. Front Immunol 2022 Dec 8;13:1019275. doi: 10.3389/fimmu.2022.1019275. eCollection 2022. PMCID: PMC9774473.
• Cai Y, Schroeder JA, Jing W, Yu H, Gurski C, Williams CB, Wang S, Dittel BN, and Shi Q. Targeting transmembrane-domain-less MOG expression to platelets prevents disease development in experimental autoimmune encephalomyelitis. Front. Immun. 2022 Oct 27; 13:1029356. doi: 10.3389/fimmu.2022.1029356. eCollection 2022. PMCID: PMC9647046.
• Shi Q and Weiler H. Blocking hemophilic arthropathy. Blood 2022 May 5;139(18):2735-2735.
• Chen Y, Luo L, Zheng Y, Zheng Q, Zhang N, Gan D, Yirga SK, Lin Z, Shi Q, Fu L, Hu J, Chen Y. Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia. Front Immunol. 2022 Apr 1;13:810620. doi: 10.3389/ fimmu.2022.810620. eCollection 2022. PMID: 35450072. PMCID: PMC9016750.
• Shi Q, Fahs SA, Matterson JG, Yu H, Perry C, Morateck PA, Schroeder JA, Rapten J, Weiler H, and Montgomery RR. A novel mouse model of type 2N VWD recapitulates human VWD and suggests dysfunctional VWF may inhibit alternative hemostatic pathways. Blood Adv 2022 May 10;6(9):2778-2790 Jan 11 PMID: 35015821 01/12/2022. Featured article. PMCID: PMC9092403.
• Schroeder JA, Kuether EA, Chen J, Jing W, Weiler H, Wilcox DA, Montgomery RR, and Shi Q. Thromboelastometry assessment of hemostatic properties in various murine models with coagulopathy and the effect of factor VIII therapies. J Thromb Haemost. 2021 Oct;19(10):2417-2427. doi: 10.1111/jth.15456. PMCID:PMC8865566.
• Schroeder JA, Chen J, Chen Y, Cai Y, Yu H, Mattson JG, Monahan PE, and Shi Q. Platelet-targeted hyperfunctional factor IX gene therapy for hemophilia B mice even with pre-existing anti-FIX immunity. Blood Adv 2021 Mar 9; 5 (5): 1224–1238. doi: 10.1182/ bloodadvances.2020004071. PMCID: PMC7948262.
• Li J, Chen J, Schroeder JA, Hu J, Williams CB, and Shi Q.* Platelet gene therapy induces robust immune tolerance even in a primed model via peripheral clonal deletion of antigen-specific T cells. Mol Ther Nucleic Acids 2021 Mar 5;23:719-730. DOI: 10.1016/j.omtn. 2020.12.026. *Corresponding author. PMID: 33575117; PMCID: PMC7851450.
• Chen Y,* Schroeder JA, Li J, Hu J, and Shi Q.* In vivo enriching genetically engineered platelets for gene therapy of hemophilia B mice. J Cell Physiol 2021 Jan;236(1):354-365 *Corresponding author. PMID: 32510630. PMCID: PMC7722216.
• Cai Y, Shi Q. Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A. Front Immunol. 2020;11:964. doi: 10.3389/fimmu.2020.00964. eCollection 2020. Review. PubMed PMID: 32595633; PubMed Central PMCID: PMC7303294.
• Chen Y, Schroeder JA, Gao C, Li J, Hu J, Shi Q. In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy. J Cell Physiol. 2020 Jun 8;. doi: 10.1002/jcp.29861. [Epub ahead of print] PubMed PMID: 32510630.
• Shi Q, Carman CV, Chen Y, Sage PT, Xue F, Liang XM, Gilbert GE. Unexpected enhancement of FVIII immunogenicity by endothelial expression in lentivirus-transduced and transgenic mice. Blood Adv. 2020 May 26;4(10):2272-2285. doi: 10.1182/bloodadvances.2020001468. PubMed PMID: 32453842; PubMed Central PMCID: PMC7252558.
• Shi Q, Mattson JG, Fahs SA, Geurts AM, Weiler H, Montgomery RR. The severe spontaneous bleeding phenotype in a novel hemophilia A rat model is rescued by platelet FVIII expression. Blood Adv. 2020 Jan 14;4(1):55-65. doi: 10.1182/bloodadvances.2019000944. PubMed PMID: 31899798; PubMed Central PMCID: PMC6960468.
• Garcia J, Flood VH, Haberichter SL, Fahs SA, Mattson JG, Geurts AM, Zogg M, Weiler H, Shi Q, Montgomery RR. A rat model of severe VWD by elimination of the VWF gene using CRISPR/Cas9. Res Pract Thromb Haemost. 2020 Jan;4(1):64-71. doi: 10.1002/rth2.12280. eCollection 2020 Jan. PubMed PMID: 31989086; PubMed Central PMCID: PMC6971331.
• Jing W, Chen J. Cai Y, Chen Y, Schroeder JA, Cui W, Johnson BD, and Shi Q.* Induction of activated T follicular helper cells is critical for anti-FVIII inhibitor development in hemophilia A mice. Blood Adv. 2019 Oct 22;3(20):3099-3110. doi: 0.1182/bloodadvances.2019000650. *Corresponding author. Featured article. Article was highlighted in “Blood Advances Highlights” by Editor-In-Chief. PMCID: PMC6849959
• Gao C, Schroeder JA, Xue F, Jing W, Cai Y, Subramaniam S, Rao S, Weiler H, Czechowicz A, and Shi Q.* Immunotoxin-mediated non-genotoxic preconditioning for platelet gene therapy of hemophilia A mice. Blood Adv. 2019 Sep 24;3(18):2700-2711. doi: 10.1182/bloodadvances.2019000516. *Corresponding author. Featured article. Article was highlighted in “Advance Notice” Newsletter by Editor-In-Chief. PMCID:PMC6759737
• Wang D, Zhang G, Gu J, Shao X, Dai Y, Li J, Pan X, Yao S, Jin Y, Huang J, Shi Q, Chen Z, and Chen S. Platelet-targeted gene therapy of murine hemophilia A using HSPCs derived from genome edited iPSCs. Haematologica 2020 Apr;105(4):e175-e179. doi: 10.3324/haematol.2019.219089. Epub 2019 Jul 11. PMCID: PMC7109733.
• Chen J, Schroeder JA, Luo X, Montgomery RR, and Shi Q. The impact of GPIbα on platelet-targeted FVIII gene therapy in hemophilia A with pre-existing anti-FVIII immunity. J Thromb Haemost. 2019 Mar;17(3):449-459. doi: 10.1111/jth.14379. PMID: 30609275. PMCID: PMC6397061.
• Luo X, Chen J, Schroeder JA, Baumgartner KC, Subramaniam M, Hu J, Williams CB, and Shi Q. Platelet gene therapy provokes targeted peripheral tolerance by clonal deletion and induction of antigen-specific regulatory T cells. Front. Immunol 2018 Sep 6; 9: 1950. Doi:10.3389/fimmu.2018.01950. PMID: 30237796. PMCID: PMC6136275.
• Shi Q. Platelet-targeted gene therapy for hemophilia. Molecular Therapy - Methods & Clinical Development 2018, 9(6): 100-108. Invited review article.
• Chen Y, Luo X, Chen J, Schroeder JA, Baumgartner KC, Hu J, and Shi Q.* Immune tolerance developed in platelet-targeted FVIII gene therapy is CD4 T cell-mediated. J Thromb Haemost. 2017 Oct;15(10):1994-2004. *Corresponding author. PMID: 28799202. PMCID: PMC5630523.
• Chen J, Schroeder JA, Luo X, and Shi Q.* The impact of von Willebrand factor on factor VIII memory immune responses. Blood Adv. 2017; Aug 22; 1(19):1565-1574. Featured article. Article was highlighted in “Advance Notice” Newsletter by Editor-In-Chief. *Corresponding author. PMID: 28920105. PMCID PMC5600162.
• Baumgartner KC, Mattson JG, Weiler H, Shi Q,* and Montgomery RR. Targeting FVIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice. J Thromb Haemost. 2017 Jan;15(1):98-109. doi: 10.1111/jth.13436. .PMCID: PMC5280575. *Corresponding author. Featured article: “In This Issue”. Tuddenham E. G. D. Platelets are a safe way to deliver factor VIII. After 13 years of preclinical research it is now time for a clinical trial.
• Haribhai, D., Luo, X., Chen, J., Jia, S., Shi, L., Schroeder, J.A., Hessner, M.J., Aster, D., Hu, J., Williams, C. B., and Shi, Q. TGFβ1 along with other platelet contents augments Treg cells to suppress anti-FVIII immune responses in hemophilia A mice. Blood Advances 2016 Dec 13, 1(2): 139-151. Article was highlighted in “Advance Notice” Newsletter by Editor-In-Chief.
• Chen, Y., Schroeder, J.A., Chen, J., Luo, X., Baumgartner, K.C., Montgomery R.R., Hu, J., and Shi, Q. The immunogenicity of platelets containing FVIII in murine hemophilia A with or without pre-existing anti-FVIII immunity. Blood 2016 Mar 10, 127(10): 1346-54. Featured article: “In This Issue”. Ragni, M.V. Platelet VIII pack evades immune detection. Blood 2016, 127(10): 1222-24. Article also got highlighted as being among the “hottest” new studies by Editor-in-Chief.
• Baumgartner, K.C, Kuether, E.L., Zhang, G., Weiler, H., Shi, Q.,* and Montgomery, R.R. Native whole blood thrombin generation assay evaluates therapeutic efficacy of plasma and platelet-derived FVIII. J Thromb Haemost. 2015 Dec; 13(12):2210-2219. * Corresponding author.
• Shi, Q.,* Schroeder, J.A., Kuether, E.L., and Montgomery, R.R. The important role of von Willebrand factor in platelet-derived factor VIII gene therapy of murine hemophilia A in the presence of inhibitory antibodies. J Thromb Haemost. 2015. 2015 July; 13(7): 1301–1309.. * Corresponding author.
• Kanaji, S., Fahs, S.A., Ware, J., Montgomery, R.R., and Shi, Q. Non-myeloablative conditioning with busulfan prior to hematopoietic stem cell transplantation leads to phenotypic correction of murine Bernard Soulier Syndrome. J Thromb Haemost. 2014 Oct; 12(10):1726-32.
• Mannucci, P,M., Shi, Q., Bonanad, S., and Klamroth, R. Novel investigations on the protective role of the FVIII/VWF complex in inhibitor development. Haemophilia 2014 Sep; 20 Suppl 6:2-16.
• Schroeder, J.A., Chen, Y., Fang, J., Wilcox, D.A., and Shi, Q*. In vivo enrichment of manipulated platelets corrects the murine hemophilic phenotype and induces immune tolerance even using a low multiplicity of infectious. J Thromb Haemost. 2014 Aug; 12(8):1283-93. * Corresponding author.
• Fahs, S.A., Hille, M.T., Shi, Q., Weiler, H., and Montgomery, R.R. Conditional knockout mouse model reveals endothelial cells as the predominant and possibly exclusive source of plasma factor VIII. Blood 2014 Jun 12, 123(24):3706-13. Featured article: “In This Issue”. Ed Tuddenham. In search of the source of factor VIII. Blood, 2014;123(24):3691. Article also got highlighted as being among the “hottest” new studies by the editors.
• Shi, Q.,* Kuether, E.L., Chen, Y., Schroeder, J.A., Fahs, S.A., and Montgomery, R.R. Platelet gene therapy corrects the hemophilic phenotype in immunocompromized hemophilia A mice transplanted with genetically manipulated human cord blood stem cells. Blood 2014, 123(3):395-403. *Corresponding author.
• Chen, Y., Schroeder, J.A., Kuether, E.L., Zhang, G., and Shi, Q*. Lentivirus-mediated platelet gene therapy corrects bleeding diathesis and induces humoral immune tolerance in hemophilia B mice. Mol Ther. 2014; 22(1):169-77. * Corresponding author.
• Du, L.M., Nurden, P., nurden, A.T., Nichols, T.C., Bellinger, D.A., Jensen, E.S., Haberichter, S.L., Merricks, E., Paymer, R.A., Fang, J., Koukouritaki, S.B., Jacobi, P.M., Hawkins T.B., Cornetta, K., Shi, Q., and Wilcox, D.A. Platelet α-granules containing human factor VIII induce hemostasis for canine hemophilia A. Nat Commun. 2013 Nov 19;4:2773:1-11 . doi: 10.1038/ncomms3773. Featured article: “Cover of Nature Home”.
• Shi, Q.*, Kuether, E.L., Schroeder, J.A., Perry, C.L., Fahs, S.A., Gil, J. C., Montgomery, R.R. FVIII inhibitors: VWF makes a difference in vitro and in vivo. J Thromb Haemost. 2012;10(11): 2328–37. Featured article: “In This Issue”. Ragni, M.V. VWF: Factor VIII Protector and Friend. J Thromb Haemost. 2012；2012;10(11): 2324–2327. * Corresponding author.
• Kuether, E.L., Fahs, S.A., Cooley, B.C., Schroeder, J.A., Chen, Y., Montgomery, R.R., Wilcox, D.A., Shi, Q.* Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-FVIII immunity. J Thromb Haemost. 2012 Aug;10(8):1570-80. Featured article: “In This Issue”. Chuah, M. and Vanderdriessche, T. Platelet-directed gene therapy overcomes inhibitory antibodies to FVIII. J Thromb Haemost 2012; 10(8): 1566-1569. *Corresponding author.
• Kanaji, S., Fahs, S.A., Shi, Q., Haberichter, S.L., and Montgomery, R.R. Contribution of platelet versus endothelial VWF to platelet adhesion and hemostasis. J Thromb Haemost. 2012;10(8):1646-52.
• Montgomery, R.R., Shi, Q. Platelet and endothelial expression of clotting factors for the treatment of hemophilia. Thromb Res. 2012 May;129 Suppl 2:S46-8.
• Shi, Q.*, Kuether, E.L., Schroeder, J.A., Fahs, S.A., Montgomery, R. R. Intravascular recovery of VWF and FVIII following intraperitoneal injection and differences from intravenous and subcutaneous injection in mice. Haemophilia. 2012;18(4), 639–46. * Corresponding author.
• Kanaji, S., Kuether, E.L., Schroeder, J.A., Fahs, S.A., Ware J., Montgomery, R.R., Shi, Q*. Lentivirus-mediated gene therapy of Bernard-Soulier Syndrome in a GPIb deficient mouse model. Mol Ther 2012 Mar;20(3):625-32. *Corresponding author.
• Montgomery, R, R. and Shi, Q. Alternative Strategies for Gene Therapy of Hemophilia. Hematology Am Soc Hematol Educ Program. 2010; 2010: 197-202.
• Shi, Q.*, Montgomery, R.R. Platelets as delivery systems for disease treatments. Advanced Drug Delivery Reviews. Adv Drug Deliv Rev. 2010;62(12):1196-203. * Corresponding author.
• Shi, Q.*, Fahs, S. A., Kuether, E. L., Cooley, B.C., Weiler, H., Montgomery, R. R. Targeting FVIII expression to endothelial cells regenerates a releasable pool of FVIII and restores hemostasis in a mouse model of hemophilia A. Blood 2010, 116(16):3049-57. Article was highlighted by Vascular Biology Publications Alert 2010. * Corresponding author.
• Zhang, G., Shi, Q., Fahs, S. A., Kuether, E.L., Walsh, C. E., Montgomery, R. R. Factor IX ectopically expressed in platelets can be stored in α-granules and corrects the phenotype of hemophilia B mice. Blood 2010, 116(8):1235-43.
• Shi, Q.*, Fahs, S. A., Wilcox, D. A., Kuether, E.L., Morateck, P.A., Mareno, N., Weiler, H., Montgomery, R. R. Syngeneic transplantation of hematopoietic stem cells (HSC) that are genetically modified to express factor VIII (FVIII) in platelets restores hemostasis to hemophilia A mice with pre-existing FVIII immunity. Blood 2008,112 (7):2713-2721. Featured article: “In This Issue”. Tuddenham E. G. D. Killing 2 birds with 1 stone. Blood 2008,112 (7):2595. * Corresponding author.
• Shi, Q.*, Wilcox, D. A., Fahs, S. A., Fang, J., Johnson B. D., Du, L., Desai, D., and Montgomery, R. R. Lentivirus-mediated platelet-derived factor VIII (FVIII) gene therapy of murine hemophilia A. J Thromb Haemost 2007, 5 (2):352-361. * Corresponding author.
• Shi, Q., Wilcox, D.A., Fahs, S.A., Weiler, H., Well, C.C., Cooley, B.C., Desai, D., Morateck, P.A., Gorski, J., and Montgomery, R.R. Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies. J Clin Invest 2006, 116 (7):1974-1982. Featured article: “In This Issue”. High, K.A. The leak stops here: platelets as delivery vehicles for coagulation factors. J Clin Invest 2006, 116 (7): 1840-1842.
• Haberichter, S.L., Shi, Q., and Montgomery, R.R. The Regulated Release of VWF and FVIII and the Biologic Implications. Pediatr Blood Cancer. 2006; 46 (5):547-53.
• Haberichter, S.L., Shi, Q., and Montgomery, R.R. The biology of von Willebrand factor and factor VIII-regulated release. Hematologica Reports 2005, 1 (6): 9-14.
• Shi, Q.*, Wilcox, D.A., Morateck, P.A., Fahs, S.A., Kenny, D., and Montgomery, R.R. Targeting GPIb(alpha) transgene expression to human megakaryocytes and forming a complete GPIb/IX complex with endogenous GPIb(Beta) and GPIX. J Thromb Haemost. 2004, 2 (11):1989-1997. J Thromb Haemost. 2003, 1:2477-2489. *Corresponding author.
• Yarovoi, H., Kufrin, D., Eslin, D.E., Thornton, M.A., Haberichter, S.L., Shi, Q., Zhu, H., Camire, R., Frkharzadeh, S.S. Kowalska, M.A., Wilcox, D.A., Montgomery, R.R., and Poncz, M. Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatment. Blood 2003, 102 (12):4006-4013.
• Shi, Q., Wilcox, D.A., Fahs, S.A., Kroner, P.A., and Montgomery, R.R. Expression of human factor VIII under control of the IIb promoter in megakaryocytic cell line as well as storage together with VWF. Mol. Genet. and Metab. 2003, 79 (1): 25-33.
• Wilcox, D.A., Shi, Q., Nurden, P., Haberichter, S.L., Rosenberg, J.B., Jonhnson, B.D., nurden, A.T., White, II G.C., and Montgomery, R.R. Induction of megakaryocytes to synthesize and store a releasable pool of human FVIII. J Thromb Haemost. 2003, 1 (12): 2477-2489.

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/qizhen.shi.1/bibliography/public/?sortby=pubDate&sdirection=descending

We seek motivated, independent, and creative researchers with excellent communication skills and the ability to work in a team environment. If you are interested in joining us, please send a CV, contact information for three references, and a cover letter detailing research interests and career goals to qshi@versiti.org.