Mount Sinai Center for Translational Medicine and Pharmacology

Our Biopharmaceutical and Nanomedicine CoRE, co-led by Satish Rojekar, PhD, and Anusha Pallapati, PhD, facilitates pre-clinical research using state-of-the-art technologies to enhance scalability, yield, and cost-saving measures for academic biologics development programs. The CoRE focuses on process development to facilitate the transition from basic research settings to large-scale manufacturing, formulation to investigate stability, and efficacy attributes and biophysical characterization to analyze structural and functional components of investigational therapeutics. We integrate instruments, techniques, and best practices to enhance the robustness and accuracy of our pre-clinical development studies that precede the phase of regulated clinical trials.

• Antibody Production: We have a stock of 250 mL, 1 L, 3 L, and 8 L spinner flasks to culture hybridomas or mammalian cells transiently or stably expressing antibodies. Three CO₂ incubators are dedicated to hybridoma and cell culture. Following cell culture, we subject the media to protein G affinity chromatography for antibody purification. The program has the capacity to produce 0.6 g and 10 g of antibodies per month from hybridomas and stable cell lines, respectively.
• Physiochemical Properties: To validate the biophysical attributes of the antibody produced, we use various techniques, including protein thermal shift, size-exclusion chromatography, mass spectrometry, nuclear magnetic resonance, circular dichroism, Fourier-transform infrared spectroscopy, ultraviolet spectrophotometry, viscometry, and turbidometry. We assess antibody purity by polyacrylamide gel electrophoresis followed by Coomassie blue staining, ligand binding assessment by protein thermal shift, and surface plasma resonance.
• Nanomedicine Capabilities: The program has the capacity to develop tailored formulations, including nanoparticles, lyophilized products, nanoemulsions, microspheres, and nanosuspensions. In addition, we can conduct pharmacokinetic and biodistribution studies for small and large molecules.
• Good Laboratory Practice Platform: This platform, led by Research Manager Anne Macdonald, study directors, and the Quality Assurance Unit, ensures that our research is reliable, repeatable, auditable, and recognized by regulatory bodies and the scientific community at large. We implement standardized procedures to define the conditions under which studies are planned, performed, recorded, reported, archived, and monitored. Data produced under the criteria for good laboratory practice for nonclinical laboratory studies conditions (21 CFR Part 58) can then be used in an investigational new drug-enabling dossier application.

Our Neurophenotyping Program, led by Co-Directors Vitaly Ryu, PhD, and Tal Frolinger, PhD, provides state-of-the-art technology to advance neuroscience research. This program has a dedicated behavioral research facility that houses four stereotactic injection platforms for optogenetic and chemogenetic studies to investigate central actions of new drugs. All stereotactic platforms are customized for microinjecting CRISPR and other viral constructs into specific brain regions. Services provided include:

• Neurobehavioral tests to examine mechanisms and therapeutic strategies in murine neuropathology, including depression, anxiety, and different domains of memory such as spatial working memory and associative learning
• Cognitive tests to include novel object recognition, Y-maze, Morris water maze, fear conditioning, light/dark box, and the forced swim test

Our Skeletal and Metabolic Phenotyping CoRE, led by Anisa Gumerova, MD, PhD, delivers analytical and phenotyping solutions for evaluating murine and other animal models of osteoporosis, obesity, and age-associated metabolic diseases. Services include:

• Non-invasive body composition analysis of fat mass, lean tissue mass, free water, and total body water in small laboratory animals, accomplished through quantitative nuclear magnetic resonance using an EchoMRI 3-in-1 body composition analyzer.
• Bone density and fat mass measurements using dual-energy X-ray absorptiometry with the iNSiGHT vet system. This technique provides two-dimensional imaging and density data on bone as well as soft tissues.
• Quantitative analysis of biomarkers employing standard and magnetic bead-based multiplex ELISA.
• Glucose and insulin tolerance tests to assess metabolic function.

The Histology CoRE, led by Anisa Gumerova, MD, PhD, provides a full range of services, including sample preparation and processing, sectioning, staining, and analysis. Services provided include:

• Paraffin and frozen histology using equipment such as an automatic tissue processor, a Microtome HM355S with STS, Leica CM3050 S cryostats, and microscopes
• Standard histological and specialized histochemical staining, as well as immunofluorescence/immunohistochemistry and RNAscope in situ hybridization
• Static and dynamic histomorphometric assessments of bone modeling and remodeling