(2ft) Predictive Modeling of Adverse Drug Reactions

Research Interests:

A single drug can cost decades and billions of dollars to bring to market, yet 90% of drugs fail at the final stages of testing once these resources have been spent. This high failure rate correlates with the exorbitant costs of medication in the United States as pharmaceutical companies work to recoup these losses. One of the major contributing factors in unsuccessful human clinical trials is the development of unpredictable adverse drug reactions. Common toxic events include hepatotoxicity, skin reactions, blood toxicity (such as anemia or thrombosis), and anaphylaxis. Such reactions are frequently undetected in pre-clinical models due to inherent differences in species physiology and an inability to model patient-to-patient variability. The development of unpredictable toxic events is generally attributed to patient-specific factors such as immune cell distribution, metabolic profile, genetics, and demographics.

I aim to establish a research group that works towards identifying and understanding those factors that result in the development of adverse drug reactions. I plan to initially focus on predicting drug-induced liver toxicity through systems biology, tissue engineering, bioinformatics, and computational modelling. My research expertise makes me uniquely qualified to address these problems. My doctoral studies focused on developing of tissue-engineered liver models for the investigation of toxicity and fibrosis. My post-doctoral studies have centered on establishing in vivo models for the early detection of metastatic cancer. Combined, my experiences provide the necessary knowledge and skills for me to build a research program that investigates the development of, currently, unpredictable liver toxicity through a systems approach. This work will detect toxicity earlier in the testing process, save time and money, and help medical teams select the safest course of treatment.

Teaching Interests:

Throughout my academic career, my teaching experiences have included lecturing over 100 students in a classroom, working with students on coursework in a one-to-one setting, and acting as a research mentor for undergraduate and graduate students. I served as an undergraduate instructional assistant at the University of Michigan for three courses (Material and Energy Balances, Separation Processes, and Chemical Reaction Kinetics) and as a graduate teaching assistant at Virginia Tech for an additional two courses (Material and Energy Balances and Heat Transfer). These courses have helped me learn how to conduct effective office hours, develop interactive lesson plans, and work with students from a variety of backgrounds. As a faculty member, I look forward to applying these skills to work towards developing a classroom and research group with a strong focus on active, personalized learning.

Education:

Postdoctoral Fellow, Department of Biomedical Engineering, University of Michigan, Current Position

Research Advisors: Lonnie Shea, Department of Biomedical Engineering

Jacqueline Jeruss, Department of Surgery

Ph.D., Department of Chemical Engineering, Virginia Tech, 2018

M.Eng., Department of Chemical Engineering, Virginia Tech, 2015

Research Advisors: Padma Rajagopalan, Department of Chemical Engineering

Marion Ehrich, Department of Pharmacology and Toxicology

B.S.E., Department of Chemical Engineering, University of Michigan, 2012

Research Advisor: Michael Solomon, Department of Chemical Engineering

Selected Publications:

*Denotes equal contribution

1. Orbach, S.M.*, G.G. Bushnell*, J.A. Ma, H.C. Crawford, M.S. Wicha, J.S. Jeruss, L.D. Shea, “Disease-induced immunomodulation at biomaterial scaffolds detects early pancreatic cancer in a spontaneous model”, Biomaterials, 2021.
2. Oakes, R.S., G.G. Bushnell, M. Orbach, P. Kandagatla, Y. Zhang, A.H. Morris, M.S. Hall, P. LaFaire, J.T. Decker, R.M. Hartfield, M.D. Brooks, M.S. Wicha, J.S. Jeruss, L.D. Shea, “Metastatic conditioning of myeloid cells at a subcutaneous synthetic niche reflects disease progression and predicts therapeutic outcomes”, Cancer Research, 2020.
3. Ford, A.J., M. Orbach, P. Rajagopalan, “Fibroblasts stimulate macrophage migration in interconnected extracellular matrices through tunnel formation and fiber alignment”, Biomaterials, 2019.
4. Orbach, S.M., J. Ford, S.E. Saverot, P. Rajagopalan, “Multi-cellular transitional organotypic models to investigate liver fibrosis”, Acta Biomaterialia, 2018.
5. Orbach S.M.,F. Ehrich, P. Rajagopalan, “High-throughput Toxicity Testing of Chemicals and Mixtures in Organotypic Multi-Cellular Cultures of Primary Human Hepatic Cells”, Toxicology in Vitro, 2018.
6. Orbach, S.M.,E. Cassin, M.F. Ehrich, P. Rajagopalan, “Investigating Acetaminophen Hepatotoxicity in Multi-Cellular Organotypic Liver Models”, Toxicology in Vitro, 2017.
7. Cassin, M.E., A.J. Ford, M. Orbach, S.E. Saverot, P. Rajagopalan, “The Design of Antimicrobial LL37-Modified Collagen-Hyaluronic Acid Detachable Multilayers”, Acta Biomaterialia, 2016.

Selected Honors and Awards:

NIH NCI: F32 Postdoctoral Fellowship; 2019 (Impact Score = 10, 1^st percentile) ($194,000 over 3 years)

University of Michigan: Postdoctoral Translational Scholar Program; 2019 ($85,000 over 3 years)

Virginia Tech: Sigma Xi PhD Research Award; 2016

Virginia Tech: Outstanding Interdisciplinary Doctoral Student; 2015

Society of Toxicology: FutureTox III Gold Level Award Recipient; 2015

University of Michigan: Magna Cum Laude; 2012