Dr. Liu's research focus is on developing, producing and evaluating new targeted anti-cancer therapies such as monoclonal antibodies, antibody-drug conjugates and gene therapies, and other innovative technologies. These projects have been actively supported by NIH and DoD grants.
Dr. X. Margaret Liu is a Professor in the William G. Lowrie Department of Chemical and Biomolecular Engineering at The Ohio State University.
As a tenured Professor with over ten years of academic research experiences and seven years of biopharmaceutical industrial experiences, Dr. X. Margaret Liu has established multiple projects in different research fields such as targeted cancer therapy, drug delivery, innovative technologies development, biomanufacturing, and anti-cancer efficacy evaluation in various preclinical animal models.
Her current research projects include antibody-drug conjugates to treat such as triple-negative breast cancer (TNBC), lung cancer and neuroendocrine cancer, mitochondria-targeted gene therapy to treat TNBC, lung cancer, and glioblastoma, targeted drug delivery, and bioprocessing and biomanufacturing.
She is working on the development of combined mitochondrial gene therapy/chemotherapy, new monoclonal antibody development and engineering (humanization), dual-targeting and dual-payload antibody-drug conjugates, and new cancer therapeutic technologies. Her research also aims to move forward to translational studies and therapy commercialization.
Previously, she was an associate professor in the Department of Biomedical Engineering at The University of Alabama at Birmingham (UAB).
Dr. Liu had worked in Biopharmaceutical and Biotechnology industry for six years before joining academia. She accomplished her Ph.D. training in Department of Chemical and Biomolecular Engineering at The Ohio State University in 2005.
Liu Laboratory projects have been actively supported by National Institutes for Health and Department of Defense grants. This research has led to three patents and a licensing agreement, with others pending.
Development of monoclonal antibodies (mAbs), adenovirus-associated viruses (AAVs), drug delivery vehicle and engineered hiPSC:
My early research focused on metabolic engineering and cell culture process development. Particularly the main goal of my Ph.D. thesis work was to increase the biochemical production by metabolic cell engineering and novel fermentation process development. During my almost seven years of biopharmaceutical and biotechnology industry work, I led anti-cancer therapeutic biologics development and production, including vector optimization, mammalian cell culture, stable production cell line development, medium and feeding nutrients development, bioreactor fed-batch cell culture process development, and scale-up to pilot plant. In my recent academic research work, my lab has developed and produced novel mAbs for cancer therapy and targeted drug delivery.
We have performed proteomics to identify potential surface markers, studied the involved intracellular signaling pathways, developed novel mAbs (IgGs) using hybridoma technology, constructed recombinant mAb in Chinese hamster ovary (CHO) cells, developed effective production platform to reach titer of 3.5 g/L using mammalian CHO cells in stirred-tank bioreactors, and purified mAbs in two chromatography columns using NGC system.
We have designed AAV vectors carrying the synthesized therapeutic genes and produced large-scale AAVs using suspensive HEK 293AAV cells in our bioreactor system (0.5-7.5L) to support animal studies.
We have developed a large-scale production of exosomes from human cells that were adapted to suspensive and serum-free culture in our stirred-tank bioreactor and liposomes using natural lipid materials, and also developed surface tagging/modification and purification technologies.
We have developed a novel robust cellular biomanufacturing to produce human T cells and hiPSC-CM cells, and confirmed the function of hiPSC- CM in animal study.
Novel targeted therapies and drug delivery approaches for cancers or other disease treatment:
As a principle investigator, I have lead several projects to develop novel targeted therapies and drug delivery vehicles.
Several surface receptors in TNBC, NET and malignant meningiomas were identified and fully evaluated. The glycosylated immunogen was designed to develop monoclonal antibody using hybridoma technology. High-productivity, high-quality and high-affinity mAbs were screened and characterized in vitro and in vivo in cell line xenograft animal model and patient tissue derived xenograft model. The cancer specific targeting, biodistribution and possible immune responses were evaluated.
Our novel mAbs were used to develop antibody-drug conjugates (ADCs) to deliver multiple highly potent small molecule drugs.
Our mAbs were used to tag the surface of exosomes and liposomes to deliver cytotoxic drugs, miRNA and AAV to treat heart diseases and cancers.
In the collaborative project with Dr. Zhou Lab, we developed a synthesized gene therapy that targets and destroys the mitochondria of cancer cells by expressing a heterologous ion channel and generating intracellular light with substrate induction.
Key regulators of host cell metabolism and physiology were investigated by creating global protein map (proteomics) and generating metabolic profiling (metabolomics).
Metabolic cell-process engineering (MCPE) facilitated antibody and biochemical production: My team has improved the production of antibody from Chinese Hamster Ovary (CHO) cells and biochemicals from cellulose biomass using various Clostridial microorganisms. The novel technology, multi-Omics guided metabolic cell-process engineering, was applied to investigate the intracellular metabolism and host cell protein expression. A mathematic model that integrates the proteomics and metabolomics data has been developed to rationally engineer host cell and the biochemical production bioprocessing.
Yang ST and Liu X*. Chapter 8. Metabolic Process Engineering for Biochemicals and Biofuels Production. New Biotechnologies for Increased Energy Security. CRC Press. Boca Raton, FL. Editor Juan Carlos Serrano-Ruiz. 2015. (Book chapter).
Xu N, Liu M, and Liu XM*. Chapter 6. Pharmacology, Pharmacokinetics, and Pharmacodynamics of Antibodies. Biosimilar. John Wiley & Sons, Inc. New Jersey. 2016. (Book chapter).
Yang S, Liu X, and Zhang Y. Metabolic Engineering. p73-118, 2006. (Book Chapter).
Ma C, Kojimab K, Xu N, Mobley J, Zhou L, Yang ST, and Liu XM*. Comparative proteomics analysis of high n-butanol producing metabolically engineered Clostridium tyrobutyricum. Journal of Biotechnology. 193, 108-119. 2015. Impact factor: 3.16.
Si Y, Zhang Y, Guan JS, Ngo HG, Totoro A, Singh AP, Chen K, Xu Y, Yang ES, Zhou L, Liu R, Liu XM*. Anti-CD47 monoclonal antibody-drug conjugate: a targeted therapy to treat triple-negative breast cancers. Vaccines. 2021. 9:882-895. https://doi.org/10.3390/vaccines9080882. Impact factor: 4.42.
Si Y, Zhang Y, Ngo HG, Guan JS, Chen Kai, Wang Q, Singh AP, Xu Y, Zhou L, Yang ES, Liu XM*. Targeted liposomal chemotherapies to treat triple-negative breast cancer. Cancers. 2021. 13(15): 3749-3763. https://doi.org/10.3390/cancers13153749. Impact factor: 6.63.
Chen K, Si Y, Ou J, Guan JS, Kim S, Ernst P, Zhang Y, Zhou L, Han X, Liu XM*. Antibody-drug conjugate to treat meningiomas. Pharmaceuticals. 2021. 14: 427-439. Impact factor: 5.86.
Ernst P, Chen K, Tang Y, Kim S, Guan J, He J, Xie M, Zhang J.J, Liu X, Zhou L. Investigation into the difference in mitochondrial-cytosolic calcium coupling between adult cardiomyocyte and hiPSC- CM using a novel multifunctional genetic probe. Pflügers Arch - Eur J Physiol. 2021. 473(3):447- 459. doi: 10.1007/s00424-021-02524-3. Impact factor: 2.77.
Kahn-Krell AM, Pretorius D, Ou J, Fast V, Litovsky S, Berry J, Liu X*, Zhang J*. Bioreactor Scalable Suspension Culture: Differentiation and Production of Cardiomyocyte Spheroids from Human Induced Pluripotent Stem Cells. Frontiers in Bioengineering and Biotechnology. 2021. 9: 674260. Impact factor: 5.48.
Si Y, Melkonian AL, Curry KC, Xu Y, Tidwell M, Liu M, Zaky AF, Liu XM*. Monoclonal antibody- based cancer therapies. C J Chem Eng. 2020. Impact factor: 3.87.
Si Y, Guan J, Xu Y, Chen K, Kim S, Zhou L, Jaskula-Sztul R, Liu XM*. Dual-targeted exosomes to facilitate combined therapies for neuroendocrine cancer treatment. Pharmaceutics. 2020. 12:1079- 1091. Impact factor: 6.73.
Si Y, Xu Y, Guan J, Chen K, Kim S, Yang E, Zhou L, Liu XM*. Anti-EGFR Antibody-drug Conjugate for Triple Negative Breast Cancer Therapy. Engineering in Life Sciences. 2020 DOI:10.1002/elsc.202000027. Impact factor: 2.0.
Si Y, Kim S, Ou J, Lu Y, Ernst P, Chen K, Whitt J, Carter A, Bibb J, Markert J, Bibb J, Chen H, Zhou L, Jaskula-Sztul R, Liu XM* Anti-SSTR2 Antibody-drug Conjugate for Neuroendocrine Tumor Therapy. Cancer Gene Therapy. 2020. 10.1038/s41417-020-0196-5. Impact factor: 4.81.
Kim S, Song J, Ernst P, Latimer MN, Ha CM, Goh KY, Ma W, Rajasekaran NS, Zhang J, Liu X, Prabhu S, Qin G, Wende AR, Young ME, and Zhou L. MitoQ regulates redox-related non-coding RNAs to preserve mitochondrial network integrity in pressure overload heart failure. Am J Physiol Heart Circ Physiol. 2020 318(3):H682-H695. PMID: 32004065. Impact factor: 3.57.
Si Y, Kim S, Zhang E, Tang Y, Jaskula-Sztul R, Markert JM, Chen H, Zhou L, Liu X*. Targeted exosomes for drug delivery: biomanufacturing, surface tagging, and validation. Biotechnology J. 2020. 15: 1900163-1900174. Impact factor: 3.54.
Ou J, Bao T, Ernst P, Si Y, Wu H, Zhou L, Yang S, Liu X*. Intracellular metabolism analysis of Clostridium cellulovorans via modeling integrating proteomics, metabolomics and fermentation. Process Biochemistry. 2020. 89: 9-19. Impact factor: 3.66.
Guenter R, Aweda T, Matos D, Jang S, Whitt J, Cheng Y-Q, Liu X, Chen H, Lapi S, Jaskula-Sztul
R. Overexpression of somatostatin receptor type 2 (SSTR2) in neuroendocrine tumors for improved [68Ga]DOTATATE imaging and treatment. Surgery. 2020. 167(1): 189-196. Impact factor: 3.36.
Herring B, Whitt J, Aweda T, Ou J, Guenter R, Lapi S, Berry J, Chen H, Liu X, Rose B, Jaskula- Sztul R. A Growth Model of Neuroendocrine Tumor Surrogates and the Efficacy of a Novel Somatostatin-Receptor Guided Antibody-Drug Conjugate: Perspectives on Clinical Response? Surgery. 2020. 167(1): 197-203. doi: 10.1016/j.surg.2019.04.073. Impact factor: 3.36.
Ernst P, Xu N, Song J, Qu J, Goldberg M, Chen H, Zhang J, Rourke B, Liu X, Zhou L. Precisely control mitochondrial membrane potential with light to manipulate cell fate decisions. Biophysical Journal. 2019. 117(4):631-645. doi: 10.1016/j.bpj.2019.06.038. Impact factor: 4.03.
Guenter R, Aweda T, Whitt J, Chang A, Cheng Y, Liu X, Chen H, Lapi S, Jaskula-Sztul R. Pulmonary carcinoid surface receptor modulation using histone deacetylase inhibitors. Cancers. 2019. 11(6): 767-780. Impact factor: 6.63.
Ou J, Si Y, Tang Y, Salzer G, Lu Y, Kim S, Qin H, Zhou L, Liu X*. Novel Biomanufacturing Platform for Large-scale and High-quality Human T Cells Production. Journal of Biological Engineering. 2019. 13: 34-46. Impact factor: 3.42.
Xu N, Ou J, Si Y, Goh K, Flanigan D, Han S, Yang Y, Yang S, Zhou L, Liu X*. Proteomics insight into the production of monoclonal antibody. Biochemical Engineering Journal. 2019. 145: 177-185. Impact factor: 3.47.
Wang Y, Li X, Liu W, Li B, Hu F, Wang L, Liu X, Cui R, and Liu R* MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration- resistant prostate cancer. Oncogene. 2019. Impact factor: 7.97.
Wu L, Yi B, Wei S, Yao D, He Y, Naik G, Bae S, Liu X, Yang W, Sonpavda G, Liu R* and Wang, L*. Losses of Foxp3 and Tsc1 Accelerate Prostate Cancer Progression through a Synergistic Transcriptional and Post-translational Regulation of c-MYC. Cancer Research. 2019. 75(8):1703- 1713. Impact factor: 9.13.
Goh K, He L, Song J, Jinno M, Rogers A, Sethu P, Halade G, Soorappan R, Liu X, Prabhu S, Darley-Usmar V, Wende A, Zhou L. Mitoquinone ameliorates pressure overload-induced cardiac fibrosis and left ventricular dysfunction in mice. Redox Biology. 2019. 21:101100. Impact factor: 11.79.
Liu Z, Che P, Mercado J, Hackney J, Friedman G, Zhang C, You Z, Ding Q, Kim K, Li H, Liu X, Markert J, Nabors B, Gillespie G, Zhao R, and Han X. Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis. Journal of Neuro-Oncology. 2018 Nov 20. doi: 10.1007/s11060-018-03047-1. Impact factor: 3.26.
Ou J, Si Y, Goh K, Yasui N, Guo Y, Song J, Wang L, Jaskula-Sztul R, Fan J, Zhou L, Liu R, Liu X*. Process development of antibody-drug conjugation production for cancer treatment. PLOS ONE. 2018. Impact factor: 3.24.
Yang R, Ernst P, Song J, Liu X, Sabine H, Wang S, Zhang J, Zhou L. Mitochondrial-mediated Oxidative CaMKII Activation Induces Early After depolarizations in Guinea Pig Cardiomyocytes: An in Silico Study. Journal of American Heart Association. JAHA. 2018 7(15):e008939. Impact factor: 5.50.
Chen T, Guo Y, Shan J, Zhang J, Shen X, Guo J*, Liu X*. Vector Analysis of Cytoskeletal Structural Tension and the Mechanisms that Underpin Spectrin-Related Forces in Pyroptosis. Antioxidants & Redox Signaling. 2018. DOI: 10.1089/ars.2017.7366. Impact factor: 7.04.
Ou J, Xu N, Ernst P, Ma C, Bush M, Goh KY, Zhao J, Zhou L, Yang S-T, Liu X*. Process engineering of cellulosic n-butanol production from corn-based biomass using Clostridium cellulovorans. Process Biochemistry. 2017. 62: 144-150. 2017. Impact factor: 3.66.
Liu X*, Ma C and Zhou L. Targeted cancer therapy. Pharmaceutical Bioprocessing. 2017. 5(2) 025- 027.
Xu N, Ma C, Ou J, Sun W, Zhou L, Hu H, and Liu X*. Comparative Proteomic Analysis of Three Chinese Hamster Ovary (CHO) Host Cells. Biochemical Engineering Journal. 2017. PII: S1369- 703X(17)30123-7. Impact factor: 3.74.
Xie C, Liu F, Dong X, Wang Y, Liu XM, and Sun Y. Modulation effect of acidulated human serum albumin on Cu2+-mediated amyloid β-protein aggregation and cytotoxicity under a mildly acidic condition. Journal of Inorganic Biochemistry. 171, 67-75. 2017. Impact factor: 3.34
Ma C, Ou J, Xu N, Yang ST, and Liu XM*. Rebalancing Redox to Improve Biobutanol Production by Clostridium tyrobutyricum. Bioengineering. 3(2), doi: 10.3390/bioengineering3010002. 2016. Impact factor: 2.24.
Xu N, Ou J, Gilani AK, Zhou L, and Liu XM*. High-Level Expression of Recombinant IgG1 by CHO K1 Platform. Frontiers of Chemical Science & Engineering. 9(3), 376-380. 2015. Impact factor: 3.75.
Ma C, Ou J, McFann S, Miller M, Liu XM*. High production of butyric acid by Clostridium tyrobutyricum mutant. Frontiers of Chemical Science & Engineering. DOI 10.1007/s11705-015- 1525-3. 9(3) 369-375. 2015. Impact factor: 3.75.
Chen J, Liu X, Wie D, and Chen G. High yields of fatty acid and neutral lipid production from cassava bagasse hydrolysate (CBH) by heterotrophic Chlorella protothecoides. Bioresource Technology. 191: 281-290, 2015. Impact factor: 7.54.
Ou J, Ma C, Xu N, Du Y, Liu XM*. Review: High Butanol Production by Regulating Carbon, Redox and Energy in Clostridia. Frontiers of Chemical Science & Engineering. DOI 10.1007/s11705-015- 1622-6. 9(3) 317-323. 2015. Impact factor: 3.75.
Xu N, Ma C, Sun W, Wu Y, and Liu XM*. Achievements and Perspectives in Host Cell Engineering. Pharmaceutical Bioprocessing. 3(4): 285-292. 2015.
Sun Y, Liu N, Wang Z, Liu X, and Yu L. Characterization of novel mixed-mode protein adsorbents fabricated from benzoyl-modified polyethyleneimine-grafted Sepharose. CHROMA. Journal of Chromatography. 1372, 157-165. 2014. Impact factor: 4.16.
Zhou L, Xu N, Sun Y, and Liu XM*. Cancer Treatment Using Targeted Biopharmaceuticals. Cancer Letters. 352, 145-151. 2014. Impact factor: 7.36.
Liu X* and Zhou L. The Application of Omics in Targeted Anticancer Biopharmaceuticals Development. Austin Journal of Biomedical Engineering. 1(1), 8-15. 2014. Impact factor: 1.20.
Lu C, Ma C, and Liu X*. High-Productivity and Low-Cost Biobutanol Production by Integrated Process Development. International Journal of Innovative Research in Science & Engineering. 2(3). ISSN 2347-3207. 2014.
Yang ST and Liu X*. Metabolic Process Engineering for Biochemicals and Biofuels Production.
Journal of Microbial and Biochemical Technology. 6(2), 1-4. 2014. Impact factor: 2.50.
Liu X*, Yang ST, and Zhou L. The Application of Omics in Pharmaceutical Bioprocessing. Journal of Biopharmaceuticals Bioprocessing. 2(1), 1-4. 2014.
Yang ST and Liu X*. Cell culture process for Biologics manufacturing: recent development and trends. Journal of Biopharmaceuticals Bioprocessing. 1(2), 133-136. 2013.
Lan T, D Wei, Yang ST, and Liu X*. Enhanced production of lignocellulases by Trichoderma viride in a rotating fibrous bed bioreactor. Bioresource Technology. 133, 125-182. 2013. Impact factor: 7.53.
Dong W, Yang ST and Liu X*. Butyric acid production from sugarcane bagasse hydrolysate by Clostridium tyrobutyricum immobilized in a fibrous-bed bioreactor. Bioresource Technology. 129, 553-560. 2013. Impact factor: 7.53.
Dhulipala P, Reddy H, Liu XM, Shannon B, Saubourin M, Piras G, Barrett B, Hassett R and Gorfien
S. Media selection for successful limiting dilution cloning of CHO cells. BioProcess International. 2011.
Ravnikar P, Liu XM, Liu J, Williams-Wright T, and Wu F. Novel cell lines for bioprocessing: friend or foe? ESACT Proceeding Paper. 2010.
Liu X*, Liu J, Williams T, Lee J, Lio P, Donahue-Hjelle L, Ravnikar P and Wu F. Protein production improvement in fed-batch culture using high osmolarity resistant CHO cells. BioProcess International. 2010. 8(4), 68-76.
Alexander P, Rudolph D, Underwood S, Desai S, and Liu X*. Optimizing microbial fermentation and mammalian cell culture: an overview. BioProcess International. 2007. 5(4), 16-24.
Liu X, and Yang ST. Kinetics of butyric acid fermentation of glucose and xylose by Clostridium tyrobutyricum wild type and mutant. Process Biochemistry. 2006. 41(4), 801-808. Impact factor: 3.66.
Liu X, Zhu Y, and Yang ST. Construction and characterization of ack deleted mutant of Clostridium tyrobutyricum for enhanced butyric acid and hydrogen production. Biotechnology Progress. 2006. 22, 1265-1275. Impact factor: 2.33.
Liu X, Zhu Y, and Yang ST. Butyric acid and hydrogen production by Clostridium tyrobutyricum ATCC 25755 and mutants. Enzyme Microbial Technology. 2005. 38, 521-528. Impact factor: 2.93.
Zhu Y, Liu X, and Yang ST Construction and characterization of pta gene deleted mutant of Clostridium tyrobutyricum for enhanced butyric acid fermentation. Biotechnology Bioengineering. 2005. 90, 154-166. Impact factor: 4.00.
Dong X, Wang Y, Liu, X, and Y Sun. Kinetic model of lysozyme renaturation with the molecular chaperone GroEL. Biotechnology Letter. 2001. 23, 1165-1169. Impact factor: 1.97.
Dong X, Bai S, Liu X, and Sun Y. Kinetics of lysozyme refolding facilitated by molecular chaperone GroEL. Huagong Xuebao. 2001. 52, 1049-1053.
Liu X, and Dong X. Molecular chaperone and protein renaturation. Chem. Ind. Eng. 2000. 17, 120- 124.
Liu X, Dong X, Zhou L, Wang Y, Zeng K, and Sun Y. Kinetics of lysozyme refolding assisted by chaperonin GroEL. Proceeding paper at National Conference on Chemical Engineering. 2000.
Zhou L, Bai S, Liu X, Zhao L, Xie S, and Sun Y. 2000. Proceeding paper. 479-482.
Liu, X.*, Ou, J., Si, Y., Zhou, L., Zhang, J., Jaskula-Sztul, R., Chen, H., Watt, J. Antibody-drug conjugate (ADC) for neuroendocrine cancer targeted therapy. Utility patent. TH Docket No. 222104- 1670. Serial No. 17/283,326. Filed on 04/07/2021. PCT/US2019/055145. Filed on 06/08/2021. Licensed to a Biopharm company (Phase I).
Liu, X.*, Zhou, L., Zhang, J., Ernst, P., Xu, N. Mitochondrial optogenetics-based gene therapy to treat multiple cancers. Utility patent. Docket No. 222104-1640. Serial No. 17/055,812. Filed on 11/16/2020.
Liu, X.*, Zhou, L. Novel anti-CD276 monoclonal antibody to target breast cancer. Provision patent. TH Docket No. 222119-8380. Serial No. 63/125,176. Filed on 12/14/2020. License negotiation on- going.
Liu, X*. Anti-CD47 monoclonal antibody for breast cancer and other cancers. Provision patent. Docket No. 222119-8450. Serial No. 63/229,807. Filed on 08/05/2021. License negotiation on-going.
Liu, X.*, Ou, J., Zhang, J., Zhou, L., Si, Y. Stirred-tank bioproduction of T cells. Docket No. 222119- 8050. Provisional patent filed on 05/24/2018.
Dempsey, J., Wu, F., Liu, X.M., Ravnikar, P., Donahue-Hjelle, L., and Gorfien, S. Methods for Impacting Cell Metabolism in Cell Culture Media. LTC Docket No. LT00421 PRO, Serial No. 61/613,448, filed on March 20, 2013.
Slade, P., Hajivandi, M., Piras, G., Liu, X., Koch, D., Hutanu, D., Bartel, C., Gorfien, S., Agnew, B. Secretome Monitoring Using Click Chemistry. Serial No. 61/492,290, filed on June 01, 2011.
Setterquist, R., Schageman, J., Liu, X.M. Cellular RNA Transcriptome Profiles. Serial No. 61/483,605, filed on May 06, 2011.
