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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 (CYP). Studies based on in vitro, structural, and computational models are used to gain more insight as to how neonates metabolize HIV drugs and the importance of CYP3A ontogeny in the liver. Research on how CYP polymorphisms in African Americans can lead to different pharmacokinetic and pharmacodynamic (PKPD) effects of certain antipsychotic drugs is also an area of active investigation in the laboratory. A third project is focused on studying the role of the ‘pathobiome’ in drug metabolism, particularly 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

In silico docking of 2α-hydroxytestosterone in CYP3A7
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, the “forever chemicals”
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.

Pseudomonas aeruginosa
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…

Human Cytochrome P450 3A7 Binding Four Copies of Its Native Substrate Dehydroepiandrosterone 3-Sulfate

J Biol Chem. 2023 Jun 29:104993. doi: 10.1016/j.jbc.2023.104993. Online ahead of print. ABSTRACT Hum…

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.

Research Instructor

Hannah WORK

Ph.D. Student

Emily GRACEY

Ph.D. Student

Michaela HVIZDAK

Ph.D. Student

Lab events

Lampe lab BBQ

Welcoming to 2 new lab members, Julieta Torres (Undergraduate student) and Abhinav Pentyala (Master …

Christmas lab lunch at Sakura Hibachi & Sushi

Volunteering at the Food Bank of the Rockies

Recent news

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…

Focus on Pharmacology

On September 25th, 2023. Dr. Lampe presented a talk at the ASPET Focus on Pharmacology series: Advan…

Drug Metabolism GRS – 2023

On July 8-9, 2023. Hannah Work presented a poster on her research work on HCV inhibitors.

ASPET 2023

On May 18-21, 2023. The LAMPE Lab presented several of their research works in poster or talk format…

International Conferences on Cytochrome P450

In May 2023, Dr. Lampe was asked by Prof. Fred Guengerich to organize the 2027 International Confere…

ISSX

In April 2023, Dr. Lampe was invited to join the International Society for the Study of Xenobiotics …

Dalhousie University

On February 7th, 2023. Dr. Lampe gave a presentation in the Department of Pharmacology at Dalhousie …

40th Mountain West SOT Meeting

On August 29-30, 2022, Michaela Hvizdak, the newest addition to the Lampe Lab, presented her researc…

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

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