Drug metabolism of ciprofloxacin, ivacaftor, and raloxifene by Pseudomonas aeruginosa cytochrome P450 CYP107S1
J Biol Chem. 2024 Jul 18:107594. doi: 10.1016/j.jbc.2024.107594. Online ahead of print. ABSTRACT Dru…
What we do…
The focus of research in the Lampe lab is understanding the role of drug metabolism and pharmacokinetics (DMPK) in drug efficacy within special population groups, with a particular emphasis on cytochrome P450 enzymes (CYPs). Studies based on in vitro, structural, and computational models are used to gain more insight as to how pregnant people, neonates, and developping fetuses metabolize antiviral drugs and the importance of CYP3A ontogeny in the liver. A second project is focused on studying the role of the ‘pathobiome’ in drug metabolism, particularly the pathogen Pseudomoas aeruginosa in cystic fibrosis patients. Lastly, the molecular mechanisms that underlie reproductive, developmental, and immunological toxicities in populations exposed to high levels of the man-made per- and polyfluoroalkyl substances (PFAS) is another research project area.
Research interests
CYP3A7 in drug metabolism and toxicity in the neonate
This research project involves functional and computational modeling of HIV drug metabolism in the neonatal liver to accurately predict drug metabolism and disposition in the neonate and developing infant. Data generated from in vitro studies using CYP3A7 recombinant enzyme, a neonatal specific CYP isoform, and neonatal human liver microsomes are being modeled to define the QSAR of CYP3A7-mediated metabolism of HIV inhibitors and to build a PBPK model for the neonatal disposition and DDI risk of these HIV drugs using the GastroPlus® software package.
CYP3A7 Crystal structure 3D flyby
PFAS and the dysregulation of oxylipins
PFAS, the “forever chemicals”, are associated with a wide variety of illnesses (hyperlipidemias, cancer, immunotoxicity, hepatotoxicity and developmental defects). The molecular mechanisms related to PFAS toxicities are not well understood. Via a collaboration with Dr. Rebecca McCullough, changes in oxylipin production and in inflammatory signals after PFAS exposure are being investigated as part of the hepatic response to these ubiquitous environmental contaminants.
Understanding the impact of Pseudomonas aeruginosa on drug metabolism and disposition
Little is known about the impact of the “pathobiome” on drug metabolism and disposition. During an infection, the pathogen is often the most abundant bacterial species present in the host and it has the potential to make a substantial contribution to the local metabolism and clearance of drugs. Our research goal is to study the ability of Pseudomonas aeruginosa, an important opportunistic pathogen of the lung in cystic fibrosis patients, to metabolize drugs and to understand how cytochrome P450 enzymes may contribute to this process.
Recent publications
Comparison of the CYP3A selective inhibitors CYP3cide, clobetasol, and azamulin for their potential to distinguish CYP3A7 activity in the presence of CYP3A4/5
The CYP3A7 enzyme accounts for ~50% of the total CYP content in fetal and neonatal livers and is the…
HCV antiviral drugs have the potential to adversely perturb the maternal-fetal communication axis through inhibition of CYP3A7 DHEA-S oxidation
The hepatitis C virus (HCV) poses a great risk to pregnant people and their developing fetus, yet no…
HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation
Drug Metab Dispos. 2024 May 16;52(6):516-525. doi: 10.1124/dmd.123.001434. ABSTRACT The hepatitis C …
Correction: Human cytochrome P450 3A7 binding four copies of its native substrate dehydroepiandrosterone 3-sulfate
J Biol Chem. 2023 Sep 30;299(10):105283. doi: 10.1016/j.jbc.2023.105283. Online ahead of print. NO A…
Consideration of Nevirapine Analogs To Reduce Metabolically Linked Hepatotoxicity: A Cautionary Tale of the Deuteration Approach
Idiosyncratic drug reactions (IDRs) in their most deleterious form can lead to serious medical compl…
Why we do it…
By understanding the differences in DMPK between the general adult population and understudied patient groups like neonates or African Americans, we are hoping in the long term to improve drug treatment which will lead to a better quality of care for these patients. We expect that our research will contribute to new and critical knowledge on drug therapy at the developmental, genetic and disease levels.
Jed
Jed LAMPE
Principal Investigator, Ph.D.
Who we are…
Jed LAMPE, Ph.D.
Principal Investigator
Sylvie KANDEL, Ph.D.
Assistant Research Professor
Emily GRACEY
Ph.D. Student
Michaela HVIZDAK
Ph.D. Student
Abhinav PENTYALA
Research Scientist
Julieta TORRES
Undergraduate Researcher
Benjamin GRACEY
Research Scientist
Lab events
Hannah’s PhD defense
Hannah defended her thesis on April 12th, 2024.
2023 Christmas Lampe lab lunch
The Lampe lab volunteered at the Food Bank of the Rockies and had lunch at North County.
Lampe lab BBQ
Welcoming to 2 new lab members, Julieta Torres (Undergraduate student) and Abhinav Pentyala (Master …
Recent news
MDO Prague
On July 07-10, 2024. Jed Lampe gave a research talk and Sylvie Kandel presented a poster.
Lampe appointed DMD Editor
On June 25th, 2024, Jed Lampe was appointed to the ASPET journal Drug Metabolism and Disposition edi…
ASPET 2024
On May 16-19, 2024. The LAMPE Lab presented several of their research works in poster or talk format…
2024 SOT Meeting
On March 10-14, 2024, Michaela Hvizdak presented her research work on PFAS in a poster format.
Johns Hopkins University
On October 4th, 2023. Dr. Lampe presented a seminar in the Department of Pharmacology and Molecular …
Rocky Mountain Discussion group
On September 29th, 2023. Dr. Lampe hosted the 2023 Annual Meeting of the Rocky Mountain Discussion g…
Where we are…
The Lampe Lab
Skaggs School of Pharmacy & Pharmaceutical Sciences
Anschutz Medical Campus
12850 E Montview Blvd,
Aurora, CO 80045
Where to find us
Pharmacy & Pharmaceutical
Sciences Building (V20)
Second floor | Room 2108
Contact us
