Biotransformation Scientist

About the role

Assist with the identification of enzymatic pathways that metabolize drug candidates in preclinical in vitro and in vivo models, including human tissue and cellular models (e.g., P450, non P450/AO/FMO, conjugative/UGT). Utilize contemporary mass spectrometry techniques (LC-MS/MS, HRMS) to identify and elucidate the structures of drug metabolites (small molecules, peptides, oligonucleotides). Contribute to the development of in vitro-to-in vivo relationships related to drug clearance and half-life predictions. Collaborate with Pharmacology and Toxicology laboratory leadership to establish Novel Approach Methodologies (NAMs) for mechanistic inquiries and platform screening processes.

Responsibilities

• Design and execute laboratory studies to identify enzymatic pathways metabolizing small molecule, peptide, and oligonucleotide therapeutics using contemporary methodologies to establish primary enzymes contributing to in vitro metabolism.
• Design and execute laboratory studies to elucidate primary drug clearance mechanisms in vitro, establishing in vitro-to-in vivo correlations for anticipated drug clearance and human half-life prediction.
• Collaborate with in vivo pharmacology and toxicology teams to execute ADME studies (non-radiolabeled), elucidating drug candidate disposition regarding absorption, distribution, metabolism, and excretion, supplemented by in vitro protein binding and blood distribution.
• For oligonucleotide and peptide molecules, design and execute in vitro studies to elucidate exonuclease/endonuclease and peptidase metabolism of drug candidates.
• Collaborate with the Toxicology Department to establish cellular models of drug metabolism, induction, and predictive toxicologic mechanisms.

Requirements

• Experience conducting in vitro and ex vivo biotransformation assays using LC–MS/MS and HRMS techniques for quantitation and structure elucidation.
• Knowledge of contemporary bioanalytical techniques, including wet chemistry separations, liquid chromatography, mass spectrometric analysis, instrument operation, and data processing.
• Knowledge of enzyme kinetics desirable.
• Ability to use software for maintaining databases to collate and catalog records and inventory.
• Independence in laboratory work and data processing.
• Working knowledge and awareness of general laboratory procedures.
• Good written and oral communication skills.
• Adherence to all safety regulations and procedures.

Qualifications

• PhD in Organic Chemistry, Biochemistry, Analytical Chemistry, or related discipline with 2-5 years of direct industrial biotransformation experience following postdoctoral training.
• M.Sc. in a related discipline with 5-7 years of direct industrial biotransformation experience.
• Working command of in vitro kinetic analysis and contemporary mathematical models for analyzing, interpreting, and modeling drug clearance, predicted half-life, and drug-drug interactions.
• Experience in mass spectrometry data collection, analysis, and interpretation via LC-MS/MS.
• Command of pharmacokinetic modeling, analysis, interpretation, and simulation is desirable.

Physical Activity and Working Conditions

• Work is normally performed in a typical interior office or laboratory environment.
• Exposure to potentially dangerous materials and situations requiring extensive safety precautions and protective equipment.
• Moderate noise level.
• Frequent involvement with radiant/electrical energy, solvents, grease, oil, irritants, acids, bases, hazardous chemicals, electro-mechanical hazards, flammable materials, and bio-hazards.
• Due to exposure to hazardous biological material (including HIV-positive specimens), immunization to Hepatitis B or other diseases may be required.

Benefits

• Health and dental coverage.
• Short- and long-term disability.
• Paid time off.
• Paid parental leave.
• 401K participation with company match.