Our Mission
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 …
The Development of Radiotheranostics for Rare and Understudied Cancers
Oncologic research generally focuses on the most common malignancies like breast and prostate cancer. The emphasis on these ubiquitous cancers is understandable, but it can leave other, less common malignancies understudied. In recent years, the Zeglis Laboratory has dedicated itself to the development of radiotheranostics for rare and understudied cancers such as endometrial cancer, squamous cell carcinoma of the anus, signet ring cell cancer, atypical rhabdoid teratoid tumors, and desmoplastic small round cell tumors.
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 four different approaches to the site-specific bioconjugation of antibodies based on (i) the chemoenzymatic manipulation of the heavy chain glycans, (ii) the reaction between thiols and payloads bearing phenyloxadiazolyl methyl sulfone moieties, (iii) the unique reactivity of specific lysine residues within antibodies, and (iv) catalytic antibodies.
The Development of Radiotheranostics for Diseases Beyond Cancer
Over the last five years, one of the Zeglis Lab’s primary mantras has been to ‘Get Weird’. Put another way, we have tried to bring the tools of radiopharmaceutical chemistry and molecular imaging to indications beyond cancer. Currently, we are working to create new tools for the clinical management of pathologies including Lyme disease, lupus nephritis, and endometriosis.
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.
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.
