Research Projects
Nanobodies for the neutralization of foodborne pathogens
In the late 1990s the startling discovery was made that Camels, llamas and alpacas have evolved a type different type of antibody. These antibodies consist solely of a heavy-chain. The antigen binding domain can be cloned to create Nanobodies (also called VHH, sdAb). Nanobodies are much smaller than conventional antibodies and can often bind places other antibody formats cannot.
Our collaborators at the National Research Council of Canada have isolated Nanobodies that bind virulence factors from the foodborne pathogens Listeria and Enterohemorrhagic E. coli. We have demonstrated that these nanobodies can prevent bacterial infection. Using structural biology we are exploring the mechanism by which these nanobodies interact with their protein targets. Aspects of this research have been funded by CSUPERB (NI grant, 2014-2015) and NIH (Score Grant - SC3GM112532, 2015-2019)
Cancer immunotherapy - Role of mucin glycosylation in the effectiveness of therapeutic antibodies
Immunotherapy has become a central pillar of cancer treatment. Antibody-based therapies have transformed the lives of thousands of patients. The mucin proteins MUC1 and MUC16 have been identified as antibody targets for the treatment of pancreatic cancer. Mucins have been linked to poor prognosis in patients and metastasis. A feature unifying cancer associated MUC1/16 are changes in protein glycosylation. Understanding how sugar modifications influences antibody binding is important for the generation of new immunotheapies.
Using a combination of X-ray crystallography, NMR, molecular dynamics, cell assays and binding studies, we aim to understand how glycosylation influences antibody binding. We have proposed a new model which explains the role that MUC1 glycosylation plays in influencing the dynamic behavior of the the protein. We have also humanized a MUC16 antibody which is currently being developed for clinical applications. This project is a ongoing collaboration with the University of Nebraska Medical Center, The University of Georgia and OncoQuest Inc. Aspects of this research have been funded by and R15 grant from the NIH (R15CA242349; 2020 - 2023); CSUBERB (JV Grant, 2018-2019), and several private research grants from OncoQuest Inc (2017-2021)
Nanobodies for cancer treatment, extending drug half-life and other therapetuic applications
Nanobodies are emerging as a powerful alternative to monoclonal antibodies for a variety of therapeutic and biotechnological applications. We are collaborating with the National Research Council of Canada on a variety of projects to understand the structural basis of how nanobodies interact with their targets. Projects include: (1) Cross-species specific and pH sensitive binding to serum albumin in order to extend the serum half-life of drugs; (2) Her2 specific nanobodies for breast cancer therapy and imaging; (3) EGFR specifc nanobides for cancer treatment and imaging; (4) development of MUC16 specific nanobodies; (5) Basic research on Holocephalin nanobodies. Aspects of this research are funded by a collaborative NRC grant (New initiatives, 2020-2021).
Cell Line Development for Protein Production
The Brooks lab works closely with its industry partner OncoQuest Inc./Quest Pharamtech Inc. to develop stable cell lines for the commercial production of therapeutic antibodies and other proteins. We have produced stable CHO cell lines expressing therapeutic antibodies targeting MUC1 and MUC16. This research has been funded by numerous private contracts from OncoQuest Inc. and Quest Pharamtech Inc.