Brian Zeglis

Dr. Brian Zeglis got his BA from Yale University and a PhD from the California Institute of Technology. He did his postdoc at the Memorial Sloan Kettering Cancer Center.

• Yale University, (B.A., 2004)
• California Institute of Technology, (Ph.D., 2009)
• Memorial Sloan Kettering Cancer Center, (Postdoctoral Fellow, 2015)

Courses taught have included:

• CHEM 36600 Inorganic Chemistry
• CHEM 39000 Inorganic Chemistry Laboratory

The research in the Zeglis Laboratory focuses on the design, synthesis, preclinical validation, and clinical translation of novel pharmaceuticals for the imaging and therapy of disease, particularly cancer. We are particularly interested in work at the intersection of molecular imaging and bioorthogonal chemistry. It is important to us that we note that in most — if not all — of our work, the members of the Zeglis Laboratory work closely with our good friends and collaborators in the Department of Radiology at Memorial Sloan Kettering Cancer Center. A few of our research directions include …

1. The Development of In Vivo Pretargeting Strategies for the Imaging and Therapy of Cancer

Over the past few years, we have been at the forefront of the development of the bioorthogonal inverse electron demand Diels-Alder reaction as a tool for radiopharmaceutical chemistry. In a series of manuscripts from 2013 to the present, we have detailed the development of an in vivo pretargeting strategy based on the rapid and selective reaction between trans-cyclooctene (TCO) and tetrazine (Tz). This approach selectively and specifically delivers radioactivity to tumor tissue while significantly reducing the overall radiation burden to the patient, facilitating a safer alternative to traditional immunoPET and radioimmunotherapy.

The Creation of Site-Specifically Labeled Immunoconjugates for Imaging and Therapy

Recent years have played witness to an incredible surge in the use of immunoconjugates for the diagnosis and therapy of cancer. Yet these tools to enable precision medicine are themselves synthesized in a surprisingly imprecise way: the indiscriminate coupling of cargoes to the lysines of the immunoglobulin. In recent years, we have pioneered two different approaches to the site-specific bioconjugation of antibodies: one based on the chemoenzymatic manipulation of the heavy chain glycans and another predicated on the reaction between thiols and payloads bearing phenyloxadiazole methyl sulfone moieties.

The Development of Optical Imaging Agents for the Diagnosis and Intraoperative Imaging of Disease

While agents bearing diagnostic and therapeutic radionuclides certainly form the core of our laboratory’s research, we also plan to branch out into the burgeoning field of optical imaging probes as well. These agents — most often labeled with fluorophores that emit near-infrared light — have the potential to be extraordinarily valuable clinical tools. While optical imaging agents no doubt have some limitations, they emit no ionizing radiation and thus are extremely attractive for diagnostic procedures as well as intraoperative applications.

Exploring the Interplay Between Radioimmunoconjugates and the Immune System

While antibodies have proven immensely effective for the delivery of diagnostic and therapeutic radionuclides to target tissues, it is important to remember that these biomolecules can interact with the body’s endogeneous immune machinery. Our laboratory has recently begun exploring the complex interplay between radioimmunoconjugates and the proteins of the immune system, specifically Fc receptors. Along these lines, we are particularly interested in developing ways to modify antibodies to attenuate these interactions and thus improve the in vivo performance of the radioimmunoconjugates.

• Rodriguez, C., Sarrett, S. M., Sebastiano, J., Delaney, S., McGlone, S. A., Hosny, M. M., Thau, S., Bournazos, S., Zeglis, B. M. “Exploring the Interplay between Radioimmunoconjugates and Fcg Receptors in Genetically Engineered Mouse Models of Cancer” ACS Pharmacology and Translational Science 7(11), 3452 (2024)
• Delaney, S., Keinänen, O., Lam, D., Wolfe, A. L., Hamakubo, T., Zeglis, B. M. “Cadherin-17 as a Target for the ImmunoPET of Adenocarcinoma” European Journal of Nuclear Medicine and Molecular Imaging 51(9), 2547 (2024)
• Sebastiano, J., Rodriguez, C., Samuels, Z. V., Pepin, K., Zeglis, B. M. “Molecular Imaging and Gynecology: Beyond Cancer” Journal of Nuclear Medicine 65(7), 998 (2024)
• Sebastiano, J., Samuels, Z. V., Kao, W. -S., Zeglis, B. M. “Site-Specific Bioconjugation and Molecular Imaging” Current Opinion in Chemical Biology 81, 102471 (2024)
• Delaney, S., Grimaldi, C., Houghton, J. K., Zeglis, B. M. “MIB Guides: Measuring the Immunoreactivity of Radioimmunoconjugates” Molecular Imaging and Biology 26(2), 213 (2024)
• MacPherson, D. S., Dave, D., Kassem, S., Doganata, S., Zeglis, B. M., Ulijn, R. V. “Tuning Supramolecular Chirality in Iodinated Amphiphilic Peptides Through Tripeptide Linker Editing” Biomacromolecules 25(4), 2277 (2024)
• Sarrett, S. M., Rodriguez, C., Delaney, S., Hosny, M. M., Sebastiano, J., Santos Coquillat, A., Keinänen, O. M., Carter, L. M., Lastwika, K. J., Lampe, P. J., Zeglis, B. M. “Evaluating CD133 as a Radiotheranostics Target in Small Cell Lung Cancer” Molecular Pharmaceutics 21(3), 1402 (2024)
• Scott, A. M., Zeglis, B. M., Lapi, S. E., Scott, P. J. H., Windhorst, A. D., Abdel-Wahab, M., Giammarile, F., Paez, D., Jalilian, A., Knoll, P., Korde, A., Vichare, S., Ayati, N., Lee, S. T., Lyashchenko, S. K., Zhang, J., Urbain, J.-L., Lewis, J. S. “Trends in Nuclear Medicine and the Radiopharmaceutical Sciences in Oncology: Workforce Challenges and Training in the Age of Theranostics” The Lancet Oncology 25(6), e250 (2024).
• Lapi, S. E., Scott, P. J. H., Scott, A. M., Windhorst, A. D., Zeglis, B. M., Abdel-Wahab, M., Baum, R. P., Buatti, J. M., Giammarile, F., Kiess, A. P., Jalilian, A., Knoll, P., Korde, A., Kunikowska, J., Lee, S. T., Paez, D., Urbain, J.-L., Zhang, J., Lewis, J. S. “Recent Advances and Impending Challenges for the Radiopharmaceutical Sciences in Oncology” The Lancet Oncology 25(6), e236 (2024).
• Yeh, R., O’Donoghue, J. A., Jayaprakasam, V. S., Mauguen, A., Min, R., Park, S., Brockway, J. P., Bromberg, J. F., Zhi, W. I., Robson, M. E., Sanford, R., Modi, S., Agnew, B. J., Lyashchenko, S. K., Lewis, J. S., Ulaner, G. A., Zeglis, B. M. “First-in-Human Evaluation of Site-Specifically Labeled 89Zr-Pertuzumab in Patients with HER2-Positive Breast Cancer” Journal of Nuclear Medicine 65(3), 386 (2024)
• Bauer, D., Cornejo, M. A., Hoang, T. T., Lewis, J. S., Zeglis, B. M. “Click Chemistry and Radiochemistry: An Update” Bioconjugate Chemistry 34(11), 1925 (2023)
• Delaney, S., Rodriguez, C., Sarrett, S. M., Dayts, E. J., Zeglis, B. M., Keinänen, O. “Unraveling the In Vivo Fate of Inhaled Micro- and Nanoplastics with PET Imaging” Science of the Total Environment 904, 166320 (2023)
• Delaney, S., Sebastiano, J., Zeglis, B. M., Keinänen, O. “Molecular Imaging, Radiochemistry, and Environmental Pollutants” Journal of Nuclear Medicine 64, 1179 (2023)
• Rodriguez, C., Delaney, S., Sebastiano, J., Sarrett, S. M., Cornejo, M. A., Thau, S., Hosny, M. M., Zeglis, B. M. Zeglis, B. M. “Site-Selective Radiolabeling Using Mushroom Tyrosinase and the Strain-Promoted Oxidation-Controlled 1,2-Quinone Cycloaddition” RSC Advances 13, 17705 (2023)
• Keinanen, O., Sarrett, S. M., Delaney, S., Rodriguez, C., Dayts, E. J., Capone, E., Sauniere, F., Ippoliti, R., Sala, G., Iacobelli, S., Zeglis, B. M. “Visualizing Galectin-3 Binding Protein Expression with ImmunoPET” Molecular Pharmaceutics 20(6), 3241 (2023)
• Delaney, S., Nagy, A., Karlström, A. E.*, Zeglis, B. M.* “Site-Specific Photoaffinity Bioconjugation for the Synthesis of 89Zr-Labeled Radioimmunoconjugates” Molecular Imaging and Biology 25, 1104 (2023)
• Bauer, D., Sarrett, S. M., Lewis, J. S., Zeglis, B. M. “Click Chemistry: A Transformative Technology in Nuclear Medicine” Nature Protocols 18(6), 1659 (2023)
• MacPherson, D., Hwang, D., Sarrett, S. M., Keinanen, O., Rodriguez, C., Rader, CC., Zeglis, B. M. “Leveraging a Dual Variable Domain Antibody to Create a Site-Specifically Modified Radioimmunoconjugate.” Molecular Pharmaceutics 20(1), 775 (2023)
• Zeglis, B. M.* Lewis, J. S.* “Click Here for Better Chemistry” New England Journal of Medicine 387(24), 2291 (2022).
• Feng, Y., Sarrett, S. M., Meshaw, R. L., Vaidyanathan, G., Cornejo, M. A., Zeglis, B. M., Zalutsky, M. R.  “Site-Specific Radiohalogenation of a HER2-Targeted Single Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent.” Journal of Medicinal Chemistry 65(22), 15358 (2022).
• Li, L. Di, L., Akther, S., Zeglis, B. M., Qiu, W. “Evolution of the Antigenic-Variability vls Locus of the Lyme Disease Pasthogen and Development of Recombinant Monoclonal Antibodies Targeting Conserved VlsE Epitopes” Microbiology Spectrum 10(5), e0174322 (2022)
• Sarrett, S. M., Rodriguez, C., Rymarczyk, G., Hosny, M., Keinänen, O., Delaney, S., Thau, S., Krantz, B. A.*, Zeglis, B. M. “Lysine-Directed Site-Specific Bioconjugation for the Creation of Radioimmunoconjugates” Bioconjugate Chemistry 33(9), 1750 (2022).
• Rodriguez, C., Delaney, S., Sarrett, S. M., Keinänen, O., Zeglis B. M. “Antibody Engineering for Nuclear Imaging and Radioimmunotherapy” Journal of Nuclear Medicine 63, 1316 (2022).
• Maitz, C. A., Delaney, S., Cook, B. E., Genady, A. R., Hoerres, R. Kuchuk, M., Makris, G., Valliant, J. F., Sadeghi, S., Lewis, J. S., Hennkens, H. M., Bryan, J. N.*, Zeglis, B. M.* “Pretargeted PET of Osteodestructive Lesions in Dogs” Molecular Pharmaceutics 19, 3153 (2022).
• Kunihiro, A. G., Sarrett, S. M., Lastwika, K. J., Solan, J. L., Pisarenko, T., Keinänen, O., Rodriguez, C., Taverne, L. R., Fitzpatrick, A. L., Li, C. I., Houghton, A. M., Zeglis, B. M.*, Lampe, P. D.* “CD133 as a Biomarker for an Autoantibody-to-ImmunoPET Paradigm for the Early Detection of Small Cell Lung Cancer” Journal of Nuclear Medicine 63, 1701 (2022).
• Macpherson, D. S., McPhee, S. A., Zeglis, B. M., Ulijn, R. V. “The Impact of Tyrosine Iodination on the Aggregation and Cleavage Kinetics of MMP-9-Responsive Peptide Sequences” ACS Biomaterials Science and Engineering. 8, 579 (2022).
• Sharma, S. K., Mack, K. N., Piersigilli, A., Pourat, J., Edwards, K. J., Keinänen, O., Jiao, M. S., Zhao, H., White, B., Brooks, C. L., de Stanchina, E., Madiyalakan, M. R., Hollingsworth, M. A., Radhakrishnan, P., Lewis, J. S., Zeglis, B. M. “ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody” Clinical Cancer Research. 28, 948 (2022).
• Keinänen, O., Dayts, E. J., Rodriguez, C., Sarrett, S. M., Brennan, J. M., Sarparanta, M., Zeglis. B. M. “Harnessing PET to Track Micro- and Nanoplastics In Vivo” Scientific Reports. 11:11463 (2021).
• Sharma, S. K., Adumeau, P., Keinänen, O., Sisodiya, V., Sarvaiya, H., Tchelepi, R., Korsen, J. A., Pourat, J., Edwards, K. A., Ragupathi, A., Hamdy, O., Saunders, L. R., Rudin, C. M., Poirier, J. T., Lewis, J. S., Zeglis, B. M. “Synthesis and Comparative In Vivo Evaluation of Site-Specifically Labeled Radioimmunoconjugates for DLL3-Targetd ImmunoPET” Bioconjugate Chemistry. 32, 1255 (2021).
• Imlimthan, S., Khng, Y. C., Keinänen, O., Zhang, W., Airaksinen, A. J., Kostiainen, M. A., Zeglis, B. M., Santos, H. A., Sarparanta, M. “A Theranostic Cellulose Nanocrystal-based Drug Delivery System with Enhanced Retention in Pulmonary Metastases of Melanoma” Small. 2007705 (2021).
• Sarrett, S. M., Keinänen, O., Dayts, E. J., Dewaele-Le Roi, G., Rodriguez, C., Carnazza, K. E., Zeglis, B. M. “In Vivo Pretargeting Based on Inverse Electron-Demand Diels Alder Click Chemistry” Nature Protocols. s41596-021-00540-2 (2021).
• Xiao, G., Annor, G. K., Fung, K., Keinänen O., Zeglis, B. M., Bargonetti, J. “Targeting Triple Negative Breast Cancer with a Nucleus-Directed p53 Tetramerization Domain Peptide” Molecular Pharmaceutics. 18, 338 (2021).
• Herth, M. M., Ametamy, S., Antuganov, D., Bauman, A., Berndt, M., Brooks, A. F., Bormans, G., Choe, Y. S., Gillings, N., Häfeli, U. O., James, M. L., Kopka, K., Kramer, V., Krasikova, R., Madsen, J., Mu, L., Neumaier, B., Piel, M., Rosch, F., Ross, R., Schibli, R., Scott, P. J. H., Shalgunov, V., Vasdev, N., Wadsak, W., Zeglis, B. M. “On the Consensus Nomenclature Rules for Radiopharmaceutical Chemistry ¾ Reconsideration of Radiochemical Conversation” Nuclear Medicine and Biology. 93, 19 (2021).
• Sarbisheh, E. K., Dewaele-Le Roi, G., Shannon, W., Tan, S., Xu, Y., Zeglis, B. M.*, Price, E. W.* “DiPODS: A Reagent for Site-Specific Bioconjugation via the Irreversible Re-bridging of Disulfide Linkages” Bioconjugate Chemistry. 31, 2789 (2020).
• Keinänen, O., Fung, K., Brennan, J. M., Zia, N., Harris, M., van Dam, E. Biggin, C., Hedt, A., Stoner, J., Donnelly, P. S., Lewis, J. S., Zeglis, B. M. “Harnessing 64Cu/67Cu for a Theranostic Approach to Pretargeted Radioimmunotherapy” Proceedings of the National Academic of Sciences of the United States of America. 117(45), 28316 (2020).
• Fung, K., Sharma, S. K., Keinänen, O., Long Roche , K., Lewis, J. S., Zeglis, B. M. “A Molecluarly Targeted Intraoperative Near-Infrared Fluorescence Imaging Agent for High-Grade Serous Ovarian Cancer” Molecular Pharmaceutics. 17, 3140 (2020).
• Fung, K., Vivier, D., Keinänen, O., Sarbisheh, E. K., Price, E. W., Zeglis, B. M. “89Zr-Labeled AR20.5: A MUC1-Targeting ImmunoPET Probe” Molecules. 25, 2315 (2020).
• White, J. M., Keinänen, O. M., Cook, B. E., Zeglis, B. M., Gibson, H. M., Viola, N. T. “Removal of Fc Glycans from [89Zr]Zr-DFO-anti-CD8 Prevents Peripheral Depletion of CD8+ T Cells” Molecular Pharmaceutics. 17(6), 2099 (2020).
• Ulaner, G. A., Carrasquillo, J. A., Riedl, C., Yeh, R., Ross, D. S., Jhaveri, K., Chandarlapaty, S., Hyman, D. M., Zeglis, B. M., Lyashchenko, S. K., Lewis, J. S. “Identification of HER2-positive metastases in patients with HER2-negative primary breast cancer using HER2-targeted 89Zr-pertuzumab PET/CT” Radiology. 296,  370 (2020).
• Imberti, C., Adumeau, P., Blower, J. E., Al Salemee, F., Torres, J. B., Lewis, J. S., Zeglis, B. M., Terry, S. Y. A., Blower, P. J. “Manipulating the In Vivo Behavior of 68Ga with Tris(hydroxypyridinone) Chelators: Pretargeting and Blood Clearance” International Journal of Molecular Sciences. 21, 1496 (2020)
• Jannetti, S. A., Zeglis, B. M., Zalutsky, M. R., Reiner, T. “Poly(ADP-ribose)polymerase (PARP) Inhibitors and Radiation Therapy” Frontiers in Pharmacology. 11, 170 (2020)
• Pirovano, G., Jannetti, S. A., Carter, L. M. Sadique, A., Kossatz, S., De Souza Franca, P. D., Maeda, M., Zeglis, B. M., Lewis, J. S., Humm, J. L., Reiner, T. R. “Targeted Brain Tumor Radiotherapy Using an Auger Emitter” Clinical Cancer Research. 26, 2871 (2020)
• Vivier, D., Fung, K., Rodriguez, C., Adumeau, P., Ulaner, G. A., Lewis, J. S. Sharma, S. K., Zeglis, B. M. “The Influence of Glycans-Specific Bioconjugation on the FcgRI Binding and In Vivo Performance of 89Zr-DFO-Pertuzumab” Theranostics. 10(4), 1746 (2020)
• Vivier, D., Fung, K., Rodriguez, C., Adumeau, P., Ulaner, G. A., Lewis, J. S. Sharma, S. K., Zeglis, B. M. The Influence of Glycans-Specific Bioconjugation on the FcRI Binding and In Vivo Performance of 89Zr-DFO-Pertuzumab Theranostics. Online Ahead of Print (2019) doi: 10.7150/thno.39089
• MacPherson, D. S., Fung, K., Cook, B. E., Francesconi, L. C., Zeglis, B. M. A Brief Overview of Metal Complexes as Nuclear Imaging Agents Dalton Trans. 48, 14547 (2019). doi: 10.1039/C9DT03039E
• Keinanen, O. M., Brennan, J. M., Membreno, R., Fung, K. C., Gangangari, K., Dayts, E. J., Williams, C. J., Zeglis, B. M. Dual Radionuclide Theranostic Pretargeting Mol. Pharm. 16(10), 4416 (2019). doi: 10.1021/acs.molpharmaceut.9b00746
• Membreno, R., Keinanen, O. M., Cook, B. E., Tully, K. M., Fung, K. C., Lewis, J. S., Zeglis, B. M. Towards the Optimization of Click-Mediated Pretargeted Radioimmunotherapy Mol. Pharm. 16(5), 2259 (2019). doi: 10.1021/acs.molpharmaceut.9b00062
• Vivier, D., Sharma, S. K., Adumeau, P., Rodriguez, C., Fung, K., Zeglis, B. M. The Impact of FcRI Binding on ImmunoPET J. Nucl. Med. 60(8), 1174 (2019). doi: 10.2967/jnumed.118.223636
• Cook, B. E., Membreno, R. M., Zeglis, B. M. Dendrimer Scaffold for the Amplification of In Vivo Pretargeting Ligations Bioconjugate Chem. 29, 2734 (2018). doi: 10.1021/acs.bioconjchem.8b00385
• Ulaner, G., Lyashchenko, S. K., Rield, C., Ruan, S., Zanzonico, P. B., Lake, D., Jhaveri, K., Zeglis, B. M., Lewis, J. S., O’Donoghue, J. A. First-in-Human HER2-targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer J. Nucl. Med. 59, 900 (2018). doi: 10.2967/jnumed.117.202010