Postdoctoral Fellow -Imaging Inflammatory Bowel Disease
Immunology Discovery at AbbVie is seeking a motivated Post-doctoral Fellow to lead the development of a large animal model of Inflammatory Bowel Disease (IBD) and in optimizing applications of pre-clinical imaging technologies, both invasive and non-invasive, in these models. The selected candidate will work in a cross-disciplinary team having backgrounds in immunology, imaging, comparative medicine, pathology, and radiochemistry and interface with multiple project teams to provide support for advancing our therapies in IBD. The project is limited to a term of 3 years and seeks to increase the efficiency of screening candidate drugs for IBD. Successful completion of the project should result in the development of a nascent translatable model of IBD and a demonstrable increase in the ability to accurately screen for and monitor of colonic mucosal healing and for candidate drug bio distribution.
Inflammatory bowel disease (IBD) is a chronic inflammatory/immune-mediated disease of the Gastrointestinal (GI) tract which can be broadly classified as Crohn's disease (CD) and ulcerative colitis (UC). Commonly used preclinical animals models of IBD such as DSS-induced IBD or T cell transfer rely on measurement of signs and symptoms such as changes in body or colon weight, to assess disease severity and therapeutic. However, these endpoints are poorly translatable for clinical application. We and others have shown that colonoscopy measurements correlate more closely with histopathology than the routinely used disease measurements such as body weight or colon weight. In addition, structural and functional improvement in the epithelial barrier is the best indicators of sustained remission. Indeed, achievement of mucosal healing is associated with a significantly lower likelihood of IBD relapse resulting in the incorporation of mucosal imaging endpoints in IBD clinical trials.
Commonly used murine models of IBD often do not recapitulate the biology of human disease, fail to respond to standard of care therapy or employ unsatisfactory endpoints. To improve the PoS (Probability of Success) of new Immunology targets and accelerate prosecution in the absence of surrogate tools we propose to develop (i) invasive (colonoscopy) and (ii) non-invasive (e.g. Multispectral Optoacoustic Tomography (MSOT) imaging of mucosal inflammation in the GI of non-humans.
Developing both invasive and non-invasive imaging of inflammation in non-human primate models of colitis would enable directly validating human therapeutics to accelerate PoC (Proof of Concept) by avoiding surrogate tool generation and potentially obviating invasive (sigmoidoscopy and colonoscopy) procedures in humans. By developing and refining the tools with which to measure inflammation, the Postdoc would have a significant impact on screening, compliance and healthcare costs associated with IBD.
Specific aims of the proposal
To establish, characterize and validate a colonic mucosal inflammation non-human primate model.
To establish, characterize and utilize preclinical imaging techniques in Non-human primate models of IBD for identification and validation of imaging biomarkers and to evaluate bio distribution of proprietary Abbvie therapeutics.
a. Demonstrate the robustness and feasibility of imaging techniques in NHP, initial studies will be carried out using (i) standard light, (ii) chroma and (iii) Confocal laser endoscopy to compare AbbVie proprietary molecules compared to anti-TNFα-mAb correlated with histology and body weight measurements.
b. Additionally, the effects of AbbVie therapeutics on blocking the inflammation in of GI tract will be visualized using Near Infra Red (NIR), MSOT, FDG-PET or an alternative noninvasive methodology and correlated with histology and body weight measurements.
c. We will evaluate the bio distribution/pharmacokinetics of AbbVie therapeutics in this model and correlate it with colonoscopy and non-invasive imaging data (Near infra-red, MSOT, FDG-PET), generated in parallel studies.
2. To expand the initial observations in specific aim 1 and evaluate possible effects of blocking inflammatory pathways using AbbVie therapeutics on the underlying IBD disease mechanisms, we will study cell trafficking (e.g. macrophages, T cells and neutrophils) to diseased tissue in-vivo using MSOT. This will be correlated with tissue inflammation as determined by colonoscopy and NIR/MSOT data generated in parallel studies.
REQUIREMENTS:DVM or PhD in immunology, biology, biomedical engineering, or veterinary sciences. The candidate should have a wide breadth of knowledge in the immunology or imaging (optical and fluorescent modalities). Large animal or primate modeling experience is preferredwith preference to experience with autioimmune models such as IBD models. Hands-on experience with multiple pre-clinical imaging modalities would be beneficial. We are seeking candidates with a demonstrated capacity to learn new disciplines and methods. The candidate must be able to discern core hypotheses which underpin a body of work and whether supporting data is critical or extraneous. The candidate should have excellent communication skills and demonstrated mastery of the written and spoken word. The candidate should have a record of publications in a well - recognized journal, should be a graduate of an accredited and nationally ranked university, should provide a narrative on why your academic training would qualify you for this position and why you have a sustained interest in this program, should provide three letters of recommendation, one at least from your PI, and preferably, one from the Chair of your department or a member of the thesis committee, must be authorized to work in the U.S, should have a proven track record of teamwork, adaptability, innovation, initiative, and integrity, and should have a global mindset to thrive in a diverse culture and environment.
Excellent oral and written communication skills.
- Excellent interpersonal, leadership & organizational skills with a demonstrated ability to work collaboratively with scientists from multiple disciplines to advance drug development.
Key AbbVie Competencies:
- Builds strong relationships with peers and cross functionally with partners outside of the team to enable higher performance.
- Learns fast, grasps the “essence” and can change the course quickly where indicated.
- Raises the bar and is never satisfied with the status quo.
- Creates a learning environment, open to suggestions and experimentation for improvement.
- Embraces the ideas of others, nurtures innovation and manages innovation to reality.
Equal Opportunity Employer Minorities/Women/Veterans/Disabled