New Capabilities in Immunopharmacology and Immunotoxicology

With the addition of an Immunotoxicologist to our laboratory, MSU In Vivo is positioned to offer a variety of services in Immnotoxicology and Immunopharmacology.

Immunopharmacology

The In Vivo Facility at Michigan State University offers both custom in vivo model and custom immunoassay development to assess immunopharmacology relevant to your drug candidate and target. These capabilities include development and analysis of target-specific immunophenotyping panels, cytokines/chemokines/inflammatory mediators, ex vivo innate immune function (ie, phagocytosis, respiratory burst, NK killing assays, etc.), and ex vivo adaptive immune function (ie, T-dependent antibody response [TDAR] assays, proliferation assays, antigen-specific activation assessments, etc.). Through the use of state-of-the-art flow cytometry, in vivo imaging, multiplex ELISA, qPCR, and microscopy technologies, we are capable of developing a wide range of custom models that assess immunopharmacology of both small molecules and biologics. The In Vivo Facility is also experienced with infectious disease, tumor, and autoimmune preclinical models. We collaborate with investigators to develop and implement proof of concept studies in disease models in order to demonstrate efficacy of therapeutics.

Pharmacodynamic Biomarker Development

The In Vivo Facility collaborates with investigators to develop custom translational target-specific pharmacodynamic (PD) biomarker assays in rodent and non-rodent species that can be utilized throughout the drug development process. It is often critical to integrate pharmacodynamic assessment of immunotherapies into preclinical toxicity studies to substantiate the safety assessment and aid in human dose determination. This has been particularly true with the recent wave of immuno-oncology biologics (ie, anti-CTLA4, anti-PD-1, anti-LAG-3, etc.), as these therapeutics have demonstrated limited toxicity in preclinical models, rendering pharmacodynamic biomarkers essential in the interpretation of safety study data. We aid in the development of robust and clear-cut pharmacodynamic biomarker assays targeted early in the drug development process that can be translated across species with the potential to be implemented in clinical trials.

Immunotoxicology

In addition to immunopharmacology model development, the In Vivo Facility collaborates with investigators to evaluate potential immunotoxicity of drug candidates, as many immunoassays can be applied to both immunotoxicology and immunopharmacology assessments. While evaluation of immunotoxicity is not recommended for all therapeutics early in the drug development process, it may be critical under circumstances where 1) the drug directly targets a component of the immune system, 2) the drug maintains structural similarity to an immunosuppressive compound, 3) previous in vitro studies suggest an effect on the immune system, or 4) the drug is intended for use in an immunocompromised population of patients. Understanding potential for immunotoxicity early in the development of a drug can identify off-target effects on the immune system or exaggerated pharmacology, which can drive important decisions regarding a lead compound and increase confidence in the successful development of a therapeutic. We work with investigators to develop non-GLP immunotoxicology studies for both biologics and small molecules using a case-by-case approach.

Investigative Immunotoxicology Model Development

The In Vivo Facility is uniquely positioned to draw upon the collective expertise of a diverse pool of faculty at Michigan State University in the fields of Immunology, Microbiology, Pharmacology, and Toxicology to drive the development of in vivo models that determine mechanisms of immunotoxicity. The occurrence of an adverse event during preclinical or clinical studies with an immunotherapeutic often precipitates the need for understanding the nature of the toxicity. Investigative in vivo studies, frequently involving transgenic or knockout models, are utilized to recapitulate these findings with the goal of determining the mechanism of toxicity.

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In Vivo Facility Welcomes Matt Bernard and Heidi Ball

The Invivo Facility is pleased to welcome Matt Bernard, PhD, and Heidi Ball, BS, to our laboratory.

Matt, an immunotoxicologist, comes to the In Vivo Facility from Bristol-Myers Squibb where he worked in Drug Safety Evaluation performing investigative research for small molecules and biologics in a GLP environment. He received his PhD in Microbiology & Immunology from the University of Rochester where he characterized the role that the inflammatory mediator, cyclooxygenase-2, plays in pathogen- and vaccination-elicited B cell immunity. Matt continued his training as a postdoctoral fellow at the La Jolla Institute for Allergy & Immunology before joining the Immunotoxicology team at Bristol-Myers Squibb. He has specialized in immunoassay development, validation, and implementation for pharmacology and toxicology studies, and has a wealth of flow cytometry experience. Matt brings his extensive knowledge in designing and conducting applied research studies in immunopharmacology and immunotoxicology to broaden our current expertise here at MSU’s In Vivo Facility.

Heidi Ball is an experienced researcher in companion animal investigations and in veterinary clinical trials. She comes from the Department of Oncology at the Michigan State University Veterinary Medical Center where she focused on tumor tissue banking and GCP veterinary clinical trials. Most recently she served as Study Coordinator for the VMC Open Heart Surgery group under the direction of Dr. Augusta Pelosi, with research emphasis on mitral valve function, degeneration, and repair. Heidi’s interests include the design, coordination and conduct of veterinary clinical trials and the study of cardiovascular disease. She received her BS in Biology from Grand Valley State University.

Wanted- A Talented Scientific Project Lead

Working at MSU In Vivo couples a fast-paced research environment with the benefits and amenities of a large research university.  We are busy and growing, and looking for self-motivated individuals to join our team.

Scientific Project Lead (Research Assistant I)

Posting Number 0122

The closing date for applications for this position is October 16, 2014.  For an application, visit http://www.jobs.msu.edu or visit our office at 1407 S Harrison, Room 110, East Lansing, MI

MSU is an Affirmative Action/Equal Opportunity Employer

Optimized Services for Academia

The MSU In Vivo Facility provides high quality standard and specialized in vivo pharmacology models, drug development services, medical device testing, and education to our industry clients.

But did you know that MSU In Vivo offers a specialized set of services optimized for academic research? We routinely provide research support to current Michigan State University faculty and staff.

And, it took awhile, but we have finally rolled out a few website additions to highlight these services.

Please click here to learn more.

Innovation is key to bacterial resistance – and defeating it

Innovation is at the heart of any successful, competitive company agenda.  It is also a defining characteristic of successful organisms.  One of the great innovators of the bacterial world is Staphylococcus aureus, which has evolved resistance to multiple antimicrobial agents in the clinical environment.  A gene that produces ß-lactamase, an enzyme that damages a key component of antibiotics like penicillin, spread through the entire species of S. aureus within a decade.  Within two years of introducing second-generation penicillin drugs that resist ß-lactamase, resistant S. aureus strains (particularly methicillin-resistant S. aureus, known as MRSA) were identified in clinical specimens.  By the 1980s, multidrug resistant traits had spread worldwide to become one of the most important causes of nosocomial infections.  Just as effective hygiene and antibiotic use policies began to bring down the frequency of MRSA in hospitals in the 1990s, MRSA strains began to show up in the general population1.  In the early 2000s, MRSA strains carrying vancomycin resistant traits were identified in clinical specimens, bringing a completely resistant bacterial pathogen closer to reality.  This possibility is far from unlikely, as bacteria have been developing resistance mechanisms for millennia2.  

Resistant pathogenic organisms are not exclusive to human populations.  A bacteria resistant to both ß-lactam drugs and carbapenem (a drug used to treat resistant bacteria) was recently identified in a squid purchased at a grocery store, for example3.  MRSA has been an increasing problem in animals for the last ten years, causing clinical disease in companion animals and horses.  It is now widely distributed in pig populations and has also been described in poultry and veal calves4.  In dairy cows, S. aureus is a common bacterial cause of mastitis and MRSA is known to cause mastitis as well.  MRSA has been confirmed in dairy cattle in multiple countries, with potential risk to animal handlers.  A recent study conducted in Southern India emphasized the zoonotic importance of methicillin resistant staphylococci associated with bovine mastitis and their potential role in transmission to animal handlers.  A total of 158 milk samples from bovine mastitis cases and 126 nasal swabs from the animal handlers were sampled in and around Pondicherry (Southern India).  Out of 158 mastitis milk samples, 19 bovine isolates were found to be MRSA.  Similarly, Out of 126 human nasal swabs, 13 human isolates were found to be MRSA.  The phenotypic and genotypic analysis carried out for the human and bovine Methicillin Resistant Staphylococci isolates were indistinguishable and epidemiologically related, which may indicate the transmission of MRSA between cattle and humans5.

While multidrug-resistant infections are rapidly increasing worldwide, few new antimicrobials capable of treating these infections are under development6.  Unless human investment and innovation can surpass that of pathogenic microbes, there could be a great cost to human health.  The MSU In Vivo Facility has experience in antimicrobial therapy models, as well as large and small animal MRSA models.  Let us help you innovate and serve this critical health need.

 

References

De Lencastre, H., Oliveira, D., & Tomasz, A. (2007). Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power. Current opinion in microbiology10(5), 428-435. doi: 10.1016/j.mib.2007.08.003.

Bhullar, K., Waglechner, N., Pawlowski, A., Koteva, K., Banks, E. D., Johnston, M. D., Barton, H. A., & Wright, G. D. (2012). Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS One, 7(4), e34953. doi: 10.1371/journal.pone.0034953.

Rubin, J. E., Ekanayake, S., & Fernando, C. (2014). Carbapenemase-producing Organism in Food, 2014. Emerging infectious diseases20(7), 1264. doi: 10.3201/eid2007.140534.

Unnerstad, H. E., Bengtsson, B., Af Rantzien, M. H., & Borjesson, S. (2013). Methicillin-resistant Staphylococcus aureus containing mecC in Swedish dairy cows. Acta Vet Scand55(6), 46. doi:10.1186/1751-0147-55-6.

Vishnupriya  S, Antony PX, HK Mukhopadhyay,  Pillai RM, Thanislass J, Vivek Srinivas VM, Sumanth Kumar R. (2014). Methicillin resistant staphylococci associated with bovine mastitis and their zoonotic importance Vet World 7(6): 422-427. doi: 10.14202/vetworld.2014.422-427.

Hersh, A. L., Newland, J. G., Beekmann, S. E., Polgreen, P. M., & Gilbert, D. N. (2012). Unmet medical need in infectious diseases. Clinical infectious diseases54(11), 1677-1678. doi: 10.1093/cid/cis275.

Come Meet with Us at ICAAC 2013

Mr. Mike Dority of the MSU in Vivo Facility will be attending the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy from September 10-13 in Denver, Colorado.  He would be happy to discuss our infectious disease modeling capabilities and answer any questions you might have.  For meeting details, please visit the website at http://www.icaac.org/.

We look forward to speaking with you.