This is unpublished


Gene Therapy
Professor, Medical Genetics


I am an academic researcher with training in molecular and applied medicine. My lab has been working on the biology and translational aspects of human adenoviruses for almost three decades. We have capitalized on mechanisms evolved by adenoviruses and developed new approaches for the treatment of cancer involving recombinant adenovirus proteins. Two of these approaches are currently being translated into the clinic. More recently, we have developed a new technology that allows for in vivo genome engineering of hematopoietic stem cells (HSCs) for the therapy of genetic blood diseases and infectious diseases. It involves the mobilization of HSCs from the bone marrow and intravenous injection of helper-dependent adenovirus vectors with tropism to HSCs. We have validated the safety and efficacy of our new approach in several murine disease models as well as in non-human primates. We showed phenotypic correction in mouse models of Sickle Cell Disease, b-thalassemia, hemophilia A, and spontaneous cancer. We used the in vivo approach to express secreted virus decoy receptors and demonstrated protection against SARS-CoV2 challenges in mice and Simian/Human Immunodeficiency Virus challenges in rhesus macaques. More recently, we have focused on in vivo genome editing with base and prime editors to treat Sickle Cell Disease in a mouse model.   I am an academic co-founder of three biotech companies (Ensoma Bio, HDT Bio, and Compliment Corp) that work on the clinical translation of our technologies.

Education & Training

MD, Second Medical Institute, Moscow, Russia (1987)

PhD, Humboldt University, Berlin, Germany (1992)

I studied Medicine and Biochemistry at the Moscow Pirogov Institute and received a PhD at the Humboldt University Berlin, Germany in 1992. After post-graduate training at the Max Planck Institute for Biochemistry, Berlin, I joined Mark Kay’s lab at the University of Washington as a post-doc in 1994 and became an independent investigator in 1998. In 2015, I was promoted to the rank of Professor of Medicine with Tenure. As of 2022, I have supervised 30 post-docs, 8 graduate students, 42 undergraduate students, and 13 visiting scientists.


Scientific Appointments

Elected member of the Western Society for Clinical Investigation (2002-present)

Elected member of the American Society for Clinical Investigation (2004-present)

Secretary, Board of Directors, American Society of Cell and Gene Therapy (2012-2016)



Postdoctoral Fellowship Award, German Academic Exchange Service (DAAD) (1994)

Postdoctoral Fellowship Award, German Research Society (DFG) (1995)

Doris Duke Charitable Foundation Award (2004)

Finalist, NIH Director’s Pioneer Award (2009)

Marsha Rivkin Foundation for Ovarian Cancer Research Award (2009)

Lester and Bernice Smith Fellow, Rivkin Center for Ovarian Cancer (2016)

Award from the “Wings of Karen” Foundation (2017)

DoD Teal Expansion Award (2018)

Senator Andy Hill CARE Breakthrough Award (2019)

Award from the Bill and Melinda Gates Foundation (2019)

Research Interests

Gene therapy (hemoglobinopathies, cancer, infectious diseases, neurodegenerative diseases)


157+ original publications (111 first/last author; 46 co-author), 23 reviews and book chapters. h-index: 60


1. Adenovirus biology: Among our contributions that have advanced the field of basic and applied adenovirus research are the discovery of two of the known three receptors that are commonly used by human adenoviruses. Two years before the death of Jesse Gelsinger, I have demonstrated that intravenously injected adenovirus vectors trigger critical innate toxicity. My lab was the first to show that adenoviruses interact with blood coagulation factors and that this influences in vivo tropism. This finding has been the basis of a new domain in adenovirus research.

Gaggar, A., Shayakhmetov, D.M., Lieber, A. (2003) CD46 is a cellular receptor for group B adenovirus. Nature                 Medicine, 9: 1408-12

Wang, H., Strauss, R., Zhang, XB., Wahl, JK, Urban, N., Drescher, C., Hemminki, A., Fender, P., Lieber, A. (2011) Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11, and 14. Nature Medicine, 17(1):96-104. pmc3074512/

Lieber, A., He, C.-Y., Meuse, L., Schowalter, D., Kirillova, I., Winther, B., Kay, M.A. (1997) The role of Kupffer cell activation and viral gene expression in early liver toxicity following infusion of first-generation adenoviruses. Journal of Virology, 71: 8798-8807  pmc192346/

Shayakhmetov DM, Gaggar A, Ni S, Li ZY, Lieber A. (2005) Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. Journal of Virology 79:7478-91.  pmc1143681/

2. In vivo HSC gene therapy for hemoglobinopathies by g-globin gene addition, reactivation of endogenous g-globin, and correction of the Sickle Cell Disease mutation by Prime editing. In 2016, we demonstrated the feasibility of a new approach to transduce HSCs in vivo after mobilization. Central to this approach was the idea that mobilized HSCs, transduced in the peripheral blood circulation, return to the bone marrow as well as the use of a new helper-dependent adenovirus vector system. We then developed this approach to treat hemoglobinopathies in mouse models.

Richter M, Saydaminova K, Yumul R, Krishnan R, Liu J, Nagy EE, Singh M, Izsvák Z, Cattaneo R, Uckert W, Palmer D, Ng P, Haworth KG, Kiem HP, Ehrhardt A, Papayannopoulou T, Lieber A. (2016) In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors. Blood. 128(18):2206-2217 pmc5095755/

Wang H, Georgakopoulou A, Psatha N, Li C, Capsali C, Samal HB, Anagnostopoulos A, Ehrhardt A, Izsvák Z, Papayannopoulou T, Yannaki E, Lieber A. (2019) In vivo hematopoietic stem cell gene therapy ameliorates murine thalassemia intermedia. J Clin Invest. 129(2):598-615 pmc6355219/

Wang H, Georgakopoulou A, Li C, Liu Z, Gil S, Bashyam A, Yannaki E, Anagnostopoulos A, Pande A, Izsvák Z, Papayannopoulou T, Lieber A. (2020) Curative in vivo hematopoietic stem cell gene therapy of murine thalassemia using large regulatory elements. JCI Insight. 5(16):e139538 pmc7455141/

Li C, Wang H, Georgakopoulou A, Gil S, Yannaki E, Lieber A (2021) In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model. Mol Ther.;29(2):822-837 pmc7854285/

Li C, Goncalves KA, Raskó T, Pande A, Gil S, Liu Z, Izsvák Z, Papayannopoulou T, Davis JC, Kiem HP, Lieber A. (2021) Single-dose MGTA-145/plerixafor leads to efficient mobilization and in vivo transduction of HSCs with thalassemia correction in mice. Blood Adv. 5(5):1239-1249 pmc7948287/

Li C, Georgakopoulou A, Newby GA, Everette KA, Nizamis E, Paschoudi K, Vlachaki E, Gil S, Anderson AK, Koob T, Huang L, Wang H, Kiem HP, Liu DR, Yannaki E, Lieber A. (2022) In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies. JCI Insight. e162939. PMC9675455

Li, C., Georgakopoulou, A., Newby, G.A., Chen, P.J., Everette, K.A., Paschoudi, K., Vlachaki, E., Gil, S., Anderson, A.K., Koob, T., Huang, L., et al. (2023). In vivo HSC prime editing rescues Sickle Cell Disease in a mouse model. Blood. 141(17): 2085-2099. PMID: 36800642

Li C, Wang H, Gil S, Germond A, Fountain C, Baldessari A, Kim J, Liu Z, Georgakopoulou A, Radtke S, Raskó T, Pande A, Chiang C, Chin E, Yannaki E, Izsvák Z, Papayannopoulou T, Kiem HP, Lieber A. (2021) Safe and  efficient in vivo hematopoietic stem cell transduction in nonhuman primates using HDAd5/35++ vectors. Mol Ther Methods Clin Dev. 24:127-14. pmc8741415/

Wang, H., Germond, A., Li, C., Gil, S., Kim, J., Kiem, H.P., and Lieber, A. (2022). In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4. Blood Adv. 6(15):4360-4372. PMID: 35679480


3. In vivo HSC gene therapy of non-hematological diseasesHemophilia A: We hypothesized that the abundance and systemic distribution of erythroid cells can be harnessed for high-level production of therapeutic proteins such as coagulation factor VIII. Using our in vivo HSC transduction approach and globin LCR-driven factor VIII expression, we achieved a phenotypic correction of bleeding in hemophilia A mice, despite high inhibitor antibody titers. Cancer prophylaxis in carriers of high-risk germ-line mutations: Population-wide testing for cancer-associated mutations has established that more than one-fifth of ovarian and breast carcinomas are associated with inherited risk. Our goal here is to use our in vivo HSC transduction approach to provide immuno-prophylaxis for mutation carriers. To control expression of transgenes, we developed a miRNA regulation system that is activated only when HSCs are recruited to and differentiated by the tumor. We tested our approach using the immune checkpoint inhibitor antiPD-L1-g1 as an effector gene. The efficacy and safety of our approach was validated in a murine ovarian cancer model with typical germ-line mutations (e.g. p53-/- brca2-/-). Infectious diseases: Furthermore, we used our in vivo approach to express secreted virus decoy receptors and demonstrated protection against a SARS-CoV2 challenges in mice and Simian/Human Immunodeficiency Virus challenges in rhesus macaques.


Wang, H., Liu, Z., Li, C., Gil, S., Papayannopoulou, T., Doering, C.B., Lieber A. (2019) High-level protein production in erythroid cells derived from in vivo transduced hematopoietic stem cells.  Blood Advances, 3(19):2883-2894 pmc6784527/

Li, C., Course, M.M., Valdmanis, P.N., Lieber, A. (2010) Prophylactic in vivo hematopoietic stem cell gene therapy with an immune checkpoint inhibitor reverses tumor growth in a syngeneic mouse tumor model. Cancer Research, 80(3):549-560  pmc7002220/

Li C, Anderson AK, Wang H, Gil S, Kim J, Huang L, Germond A, Baldessari A, Nelson V, Bar KJ, Peterson CW, Bui J, Kiem HP, Lieber A. (2023). Stable HIV decoy receptor expression after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV. Mol Ther. 2023 Apr 5;31(4):1059-1073 PMID: 36760126

Wang H, Li C, Obadan AO, Frizzell H, Hsiang TY, Gil S, Germond A, Fountain C, Baldessari A, Roffler S, Kiem HP, Fuller DH, Lieber A. (2022) In Vivo Hematopoietic Stem Cell Gene Therapy for SARS-CoV2 Infection Using a Decoy Receptor. Hum Gene Ther. 2022 Apr;33(7-8):389-403 PMID: 35057635

4. Clinical translation

- epithelial junction opener (JO)-based approach to improve drug penetration in solid tumors. A central resistance mechanism is the maintenance of tight junctions between malignant cells that prevent drug penetration into the tumor. We have generated JO, a small recombinant protein that binds to desmoglein 2 (DSG2), a junction protein that is overexpressed in epithelial cancers. Binding of JO to DSG2 triggers signaling pathways and results in transient opening of tight junctions between tumor cells. This, in turn, increased the intratumoral penetration and efficacy of monoclonal antibodies and chemotherapeutic drugs. The FDA approved recently an IND for JO in combination with PEGylated liposomal doxorubicin in patients with recurrent ovarian/fallopian tube cancer. A phase I trial will be initiated at the FHCRC in summer 2023. This is an example of our ability to translate findings from the bench to bedside. 


Beyer I, van Rensburg R, Strauss R, Li Z, Wang H, Persson J, Yumul R, Feng Q, Song H, Bartek J, Fender P, Lieber A. (2011) Epithelial Junction Opener JO-1 Improves Monoclonal Antibody Therapy of Cancer. Cancer Research, 71(22):7080-90. pmc3217128/

Beyer, I., Persson, J., Song, H., Cao, H., Feng, Q., Yumul, R., van Rensburg, R., Li, ZY, Berenson, R., Carter, D., Roffler, S., Drescher, C., Lieber, A. (2012) Co-administration of epithelial junction opener JO-improves the efficacy and safety of chemotherapeutic drugs. Clinical Cancer Research, 18(12):3340-51 pmc3547677/

Yumul R, Richter M, Lu ZZ, Saydaminova K, Wang H, Wang CH, Carter D, Lieber A. (2016) Epithelial Junction Opener Improves Oncolytic Adenovirus Therapy in Mouse Tumor Models. Hum Gene Ther.27(4):325-37. pmc4840918/

Kim J, Li C, Wang H, Kaviraj S, Singh S, Savergave L, Raghuwanshi A, Gil S, Germond A, Baldessari A, Chen B, Roffler S, Fender P, Drescher C, Carter D, Lieber A. (2022) Translational development of a tumor junction opening technology. Sci Rep. 2022 May 11;12(1):7753. PMID: 35562182


- Ad35K++ based approach to sensitize cancer cells to complement-dependent cytotoxicity (CDC) triggered by monoclonal antibodies. Many mAbs used for cancer therapy, upon binding, kill tumor cells through activation of CDC. As an escape mechanism, tumors upregulate complement inhibitory membrane proteins, specifically CD46. We have developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to CDC triggered by mAbs.  We generated an affinity-enhanced Ad35-derived fiber knob (Ad35K++), a small recombinant protein that can be produced in E.coli and easily purified. We demonstrated the utility of the combination of Ad35K++ and several commercially available mAbs (rituximab, ofatumumab, alemtuzumab, gemtuzumab, trastuzumab) in dramatically improving CDC-mediated cell killing as demonstrated in vitro with several tumor cell lines and primary tumor cells as well as in vivo, in tumor xenograft models. Our studies in Macaca fascicularis provided evidence that intravenous Ad35K++ injection increases the effectiveness of rituximab in depletion of peripheral blood CD20-positive cells. Towards the clinical application of Ad35K++, we established a cGMP-compliant manufacturing protocol and received IND approval for a combination therapy of Ad35K++ and rituximab in patients with rituximab-refractory B-cell malignancies. A corresponding IND application covering the manufacturing, toxicology studies, and a phase I trial was approved by the FDA in December 2018. We are currently raising the funds for the clinical trial.

Wang H, Liu Y, Li Z, Tuve S, Stone D, Kalyushniy O, Shayakhmetov D, Verlinde CL, Stehle T, McVey J, Baker A, Peng KW, Roffler S, Lieber A. (2008) In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46. Journal of Virology, 82(21):10567-79, PMID: 18753195

Wang, H., Liu, Y., Li, ZY, Liang, M., Lieber A. (2009) A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy.  Blood, 115(3):592-600, PMID: 19965652

Beyer I, Cao H, Persson J, Wang H, Liu Y, Yumul R, Li Z, Woodle D, Manger R, Gough M, Rocha D,     Bogue J, Baldessari A, Berenson R, Carter D, Lieber A. (2013) Transient removal of CD46 is safe and increases B-cell depletion by rituximab in CD46 transgenic mice and rhesus macaques Molecular Therapy 21(2):291-9, PMID: 23089733

Hay J, Carter D, Lieber A, Astier AL. (2014) Recombinant Ad35 adenoviral proteins as potent modulators of human T cell activation. Immunology. 144(3):453-60, PMID: 25251258 

Richter M, Yumul R, Saydaminova K, Wang H, Gough M, Baldessari A, Cattaneo R, Lee F, Wang CH, Jang H, Astier A, Gopal A, Carter D, Lieber A (2016) Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic. Mol Ther Methods Clin Dev 5:16013. PMID: 27069950

Koob, T., Fromm, J., Gopal, A., Carter, D. Lieber, A., Wang, H. (2023) CD46 and CD59 inhibitors additively enhance complement-dependent cytotoxicity of anti-CD38 mAbs Daratumumab and Isatuximab in human multiple myeloma cells.  26th Annual ASGCT meeting, abstract #1570