A5064949069- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Pancreatic function and diabetes
- Cell Adhesion Molecules Research
- Enzyme Catalysis and Immobilization
- Photoacoustic and Ultrasonic Imaging
- Cellular Mechanics and Interactions
- Nanofabrication and Lithography Techniques
- Optical Imaging and Spectroscopy Techniques
- Biosensors and Analytical Detection
- Biomedical and Engineering Education
- Mathematical Biology Tumor Growth
- Amino Acid Enzymes and Metabolism
- Diet, Metabolism, and Disease
- Microbial Metabolic Engineering and Bioproduction
- Nanoplatforms for cancer theranostics
- Engineering Education and Pedagogy
- Immunotherapy and Immune Responses
- Innovative Teaching Methods
- Experimental Learning in Engineering
- Orthopedic Infections and Treatments
- 3D Printing in Biomedical Research
- Plant nutrient uptake and metabolism
Novartis (United States)
2023-2024
University of Michigan
2014-2023
Michigan United
2020
Ann Arbor Center for Independent Living
2017
Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied seven current FDA-approved antibody-drug conjugates (ADC). However, variety pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering development new drugs. Here, we use series prostate-specific membrane antigen-binding single-domain (Humabody) ADC constructs demonstrate that tissue penetration...
Biocatalysts, especially enzymes, have the ability to catalyze reactions with high product selectivity, utilize a broad range of substrates, and maintain activity at low temperature pressure. Therefore, they represent renewable, environmentally friendly alternative conventional catalysts. Most current industrial-scale chemical production processes using biocatalysts employ soluble enzymes or whole cells expressing intracellular enzymes. Cell surface display systems differ by presenting...
A computational model predicting bystander payload distribution as a function of controllable design parameters for guiding efficient clinical ADC development.
With the recent approval of 3 new antibody drug conjugates (ADCs) for solid tumors, this class drugs is gaining momentum targeted treatment cancer. Despite significant investment, there are still fundamental issues that incompletely understood. Three recently approved ADCs contain payloads exhibiting bystander effects, where payload can diffuse out a cell into adjacent cells. These effects often studied using mosaic antigen positive and negative However, distance these in tumor tissue while...
Several antibody-drug conjugates (ADC) showing strong clinical responses in solid tumors target high expression antigens (HER2, TROP2, Nectin-4, and folate receptor alpha/FRα). Highly expressed tumor often have significant low-level normal tissues, resulting the potential for target-mediated drug disposition (TMDD) increased clearance. However, ADCs do not cross-react with tissue animal models used to test efficacy (typically mice), impact of ADC binding on response remains unclear. An...
Abstract Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes irreversible damage to the joints. However, effective drugs exist can stop progression, leading intense interest in early detection and treatment monitoring improve patient outcomes. Imaging approaches have potential for detection, but current methods lack sensitivity and/or are time-consuming expensive. We examined routes self-administration of molecular imaging agents form subcutaneous oral delivery...
Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical can achieve. However, the high cost and risks of ionizing radiation several molecular modalities have prevented a feasible scalable approach screening. Clinical studies demonstrated ability to detect tumors using nonspecific probes indocyanine green, but lack required intravenous contrast agent...
The diabetes community has long desired an imaging agent to quantify the number of insulin-secreting β-cells, beyond just functional equivalents (insulin secretion), help diagnose and monitor early stages both type 1 2 mellitus. Loss in β-cells can be masked by a compensatory increase function remaining cells. Since form only about 1% pancreas decrease as disease progresses, few agents, such exendin, have demonstrated clinical potential detect drop already scarce signal. However, translation...
We have recently developed a simple, reusable and coupled whole-cell biocatalytic system with the capability of cofactor regeneration biocatalyst immobilization for improved production yield sustained synthesis. Described herewith is experimental procedure development such consisting two E. coli strains that express functionally complementary enzymes. Together, these enzymes can function co-operatively to mediate expensive cofactors improving product bioreaction. In addition, method...
Antibody drug conjugates (ADC) are a promising class of oncology therapeutics consisting an antibody conjugated to payload via linker. DYP688 is novel ADC comprising signaling protein inhibitor (FR900359) that undergoes unique on-antibody inactivation in plasma, resulting complex pharmacology. To assess the impact FR on pharmacology and clinical developability, we performed translational modeling preclinical PK tumor growth inhibition (TGI) data, accompanied by mechanistic Krogh cylinder...
In situ clinical measurement of receptor occupancy (RO) is challenging, particularly for solid tumors, necessitating the use mathematical models that predict tumor to guide dose decisions. A potency metric, average free tissue target initial ratio (AFTIR), was previously described based on a mechanistic compartmental model and informative near-saturating regimens. However, metric fails at clinically relevant subsaturating antibody doses, as cannot capture spatial heterogeneity distribution...
Limitations in current imaging tools have long challenged the of small pancreatic islets animal models. Here, we report first development and vivo validation testing a broad-spectrum high-absorbance near-infrared optoacoustic contrast agent, E4x12-Cy7. Our tracer is based on amino acid sequence exendin-4 targets glucagon-like peptide-1 receptor (GLP-1R). Cell assays confirmed that E4x12-Cy7 has high-binding affinity (dissociation constant, Kd, 4.6 ± 0.8 nM). Using multispectral tomography,...
We have recently developed a simple, reusable and coupled whole-cell biocatalytic system with the capability of cofactor regeneration biocatalyst immobilization for improved production yield sustained synthesis. Described herewith is experimental procedure development such consisting two E. coli strains that express functionally complementary enzymes. Together, these enzymes can function co-operatively to mediate expensive cofactors improving product bioreaction. In addition, method...
Abstract Limitations in current imaging tools have long challenged the of small pancreatic islets animal models. Here, we report first development and vivo validation testing a broad spectrum high absorbance near infrared optoacoustic contrast agent, E4 x12 -Cy7. Our tracer (E4 -Cy7) is based on amino acid sequence exendin-4 targets glucagon-like peptide-1 receptor (GLP-1R). Cell assays confirmed that -Cy7 has binding affinity (IC 50 = 4.6 ± 0.8 nM). Using multi-spectral tomography (MSOT),...
<div>Abstract<p>Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied seven current FDA-approved antibody–drug conjugates (ADC). However, variety pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering development new drugs. Here, we use series prostate-specific membrane antigen–binding single-domain (Humabody) ADC constructs demonstrate...
<div>Abstract<p>Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied seven current FDA-approved antibody–drug conjugates (ADC). However, variety pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering development new drugs. Here, we use series prostate-specific membrane antigen–binding single-domain (Humabody) ADC constructs demonstrate...
<p>This file contains information on the methods used during drug formulation, reaction, and purification as well an in-depth description of in vitro assays, experimental/computational spheroid work, tumor growth measurements. The figures tables provide characterization therapeutic constructs, rationale for efficacy study dosing, Krogh Cylinder simulation parameters.</p>
<p>This file contains information on the methods used during drug formulation, reaction, and purification as well an in-depth description of in vitro assays, experimental/computational spheroid work, tumor growth measurements. The figures tables provide characterization therapeutic constructs, rationale for efficacy study dosing, Krogh Cylinder simulation parameters.</p>