Biography

Xin Ge, PhD, is an Associate Professor of Molecular Medicine, and the Kay and Ben Fortson Distinguished Chair in Neurodegenerative Disease Research at the University of Texas Health Science Center at Houston. He is a regular faculty member at the MD Anderson-UTHealth Graduate School of Biomedical Sciences. Prior to joining UTHealth Houston, he was Assistant and Associate Professor of Chemical and Environmental Engineering at University of California, Riverside in 2011-2021.

Dr. Ge’s research focuses on developing biologics, such as monoclonal antibodies (mAbs), T-cell receptors (TCRs) and therapeutic enzymes. His laboratory is committed to inventing enabling technologies that facilitate biologics discovery and engineering, which are important but difficult or even impossible with current methods. Bypassing the limits associated with what nature offers, Dr. Ge and his team apply engineering strategies and streamline a set of in vitro approaches including synthetic library construction, structure-aided design, mammalian cell display, functional selection, and repertoire deep sequencing. Combinations of these novel approaches provide a powerful means for generation and optimization highly potent biologics relevant to disease diagnosis and treatment.

Professional Highlights

  • Maximizing Investigators’ Research Award (R35), NIGMS, 2021
  • Faculty Early Career Development Program (CAREER), NSF, 2015
  • Postdoctoral Fellowship, NSERC, 2008
  • Ad hoc reviewer for 7 NIH study sections, 7 NSF review panels, and 5 foreign national agencies
  • Graduated 7 PhD and 7 MS; and supervised 11 postdocs and 5 research scientists

Education

Postdoctoral Fellowship, 2008-2011
University of Texas at Austin
Postdoctoral Fellowship, 2008
McMaster University
Ph.D. Chemical Engineering, 2008
McMaster University
M.S. Chemical and Biochemical Engineering, 2003
Tsinghua University
B.S. Chemical Engineering, 2000
Tsinghua University

Areas of Interest

Research Interests

Protease Inhibitory mAbs. Proteases are important drug targets, but their compound inhibitors largely failed due to lack of specificity while conventional mAb technologies are incompetent for the isolation of inhibitors. To address these issues, my laboratory has been developing a series of novel technologies, notably camelid-inspired convex paratope human antibody library design and functional selection/screening. Applying these engineering strategies, panels of potent and highly specific mAbs have been facilely discovered, to inhibit numerous proteases of biomedical importance. Our protease inhibitory mAbs have exhibited significant therapeutic efficacy in animal models of melanoma, breast cancer, neuropathic pain, obesity, dietetics, SARS-CoV-2, stroke, and diabetic neuropath. Several US/WO patents have been granted and many our mAbs are licensed to pharmaceutical companies for further development.

Directed Evolution in Mammalian Cells. Construction of combinatorial libraries in mammalian cells offers unique opportunities for therapeutic development that microbial platforms cannot provide. Apart from commonly used lentivirus or CRISPR/Cas9, we focus on recombinase-mediated transgene integration systems and develop a series of optimizations to achieve desired criteria of library construction in mammalian cells – transgene stability, monoclonality, large-diversity, and high-fidelity. Applying our novel approaches, Fc mutants were engineered with enhanced affinity and selectivity for individual FcγRs and improved cytotoxic potency. We also achieved rapid discovery of TCR-like CARs that effectively elicit potent and persistent T cell responses toward cancer associated antigens without cross-reactivities. This platform technology is widely applicable for the development of a variety of immunotherapy modalities including CAR-T, TCR-T, and T cell engagers against cancer, infections and autoimmune diseases.

https://med.uth.edu/imm/biopharmaceutical-discovery/

Publications

Selected publications (#equal contribution, *corresponding author)

  • Zening Wang, Minhyo Kang, Afshin Ebrahimpour, Chuan Chen, Xin Ge*. 2024. Fc Engineering by Monoclonal Mammalian Cell Display for Improved Affinity and Selectivity Towards FcgRs. Antibody Therapeutics, 7:209-220.
  • Chuan Chen#, Zening Wang#, Minhyo Kang, Ki Baek Lee, Xin Ge*. 2023. High-Fidelity Large-Diversity Monoclonal Mammalian Cell Libraries by Cell Cycle Arrested Recombinase-Mediated Cassette Exchange (aRMCE). Nucleic Acid Research, 51:e113.
  • Hyunjun Choe, Tara Antee, Xin Ge*. 2023. Substrate Derived Sequences Act as Subsite-Blocking Motifs in Protease Inhibitory Antibodies. Protein Science, 32:e4691.
  • Yutaka Matsuoka, Kenta Furutani, Ki Baek Lee, Xin Ge*, Ru-Rong Ji*. 2023. Inhibition of Diabetic Neuropathic Pain by Intrathecal and Intravenous Administration of MMP-9 Monoclonal Antibody in Mice. Journal of Pain, 24:46.
  • Dong Hyun Nam#, Ki Baek Lee#, Evan Kruchowy, Henry Pham, Xin Ge*. 2020. Protease Inhibition Mechanism of Camelid-Like Synthetic Human Antibodies. Biochemistry, 59:3802-3812.
  • Ki Baek Lee, Zachary S Dunn, Tyler Lopez, Zahid Mustafa, Xin Ge*. 2020. Generation of Highly Selective Monoclonal Antibodies Inhibiting a Recalcitrant Protease Using Decoy Designs. Biotechnology and Bioengineering 117:3664-3676.
  • Tyler Lopez, Zahid Mustafa, Chuan Chen, Ki Baek Lee, Aaron Ramirez, Chris Benitez, Xin Luo, Ru-Rong Ji, Xin Ge*. 2019. Functional Selection of Protease Inhibitory Antibodies. PNAS, 116:16314-16319.
  • Ki Baek Lee, Zachary S Dunn, Xin Ge*. 2019. Reducing Proteolytic Liability of an MMP-14 Inhibitory Antibody by Site-Saturation Mutagenesis. Protein Science, 28:643-653.
  • Kuan-Hui E. Chen*, Chuan Chen, Tyler Lopez, Kelly C. Radecki, Karissa Bustamante, Mary Y. Lorenson, Xin Ge, Ameae M. Walker. 2018. Use of a Novel Camelid-inspired Human Antibody Demonstrates the Importance of MMP-14 to Cancer Stem Cell Function in the Metastatic Process. Oncotarget, 9:29431-29444.
  • Tyler Lopez, Chen Chuan, Aaron Ramirez, Kuan-Hui E Chen, Mary Y Lorenson, Chris Benitez, Zahid Mustafa, Henry Pham, Ramon Sanchez, Ameae M Walker, Xin Ge*. 2018. Epitope Specific Affinity Maturation Improved Stability of Potent Protease Inhibitory Antibodies. Biotechnology and Bioengineering, 115:2673-2682.
  • Tyler Lopez, Aaron Ramirez, Chris Benitez, Zahid Mustafa, Henry Pham, Ramon Sanchez, Xin Ge*. 2018. Selectivity Conversion of Protease Inhibitory Antibodies. Antibody Therapeutics, 1:55-63.
  • Tyler Lopez, Dong Hyun Nam, Evan Kaihara, Zahid Mustafa, Xin Ge*. 2017. Identification of Highly Selective MMP-14 Inhibitory Fabs by Deep Sequencing. Biotechnology and Bioengineering, 114:1140-1150.
  • Dong Hyun Nam, Kuili Fang, Carlos Rodriguez, Tyler Lopez, Xin Ge*. Generation of Inhibitory Monoclonal Antibodies Targeting Membrane-Type 1 Matrix Metalloproteinase by Motif Grafting and CDR Optimization. Protein Engineering, Design and Selection, 30:113-118.
  • Dong Hyun Nam, Xin Ge*. 2016. Direct Production of Functional Matrix Metalloproteinase-14 Without Refolding or Activation and its Application for In Vitro Inhibition Assays. Biotechnology and Bioengineering, 113:717-723.
  • Xin Cathy Li, Christopher Wang, Ashok Mulchandani, Xin Ge*. 2016. Engineering Soluble Human Paraoxonase 2 for Quorum Quenching. ACS Chemical Biology, 11:3122-3131.
  • Dong Hyun Nam, Carlos Rodriguez, Albert G Remacle, Alex Y Strongin, Xin Ge*.  2016.  Active-Site MMP-Selective Antibody Inhibitors Discovered from Convex Paratope Synthetic Libraries. PNAS, 113:14970-14975.

Google Scholar profile page – https://scholar.google.com/citations?user=zOMUhtwAAAAJ&hl=en