Per- and polyfluoroalkyl substances (PFAS) inhibit cytochrome P450 CYP3A7 through direct coordination to the heme iron and water displacement
J Inorg Biochem. 2023 Jan 4;240:112120. doi: 10.1016/j.jinorgbio.2023.112120. Online ahead of print.…
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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.
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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.
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Recent publications
Cefadroxil Comparable to Cephalexin: Minimum Inhibitory Concentrations among Methicillin-Susceptible Staphylococcus aureus Isolates from Pediatric Musculoskeletal Infections
Microbiol Spectr. 2022 Jun 22:e0103922. doi: 10.1128/spectrum.01039-22. Online ahead of print. ABSTR…
Identification of Aloe-derived natural products as lead scaffolds for SARS-CoV-2 main protease (Mpro ) inhibitors
FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.R2065. ABSTRACT In the past two years, …
Identification of Aloe-derived natural products as prospective lead scaffolds for SARS-CoV-2 main protease (Mpro) inhibitors
In the past two years, the COVID-19 pandemic has caused over 5 million deaths and 250 million infect…
Pseudomonas aeruginosa cytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE
Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen that is highly prevalent in i…
Characterization of fluorescent probe substrates to develop an efficient high-throughput assay for neonatal hepatic CYP3A7 inhibition screening
CYP3A7 is a member of the cytochrome P450 (CYP) 3A enzyme sub-family that is expressed in the fetus …
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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.
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Who we are…
Jed LAMPE, Ph.D.
Principal Investigator
Sylvie KANDEL, Ph.D.
Research Instructor
Hannah WORK
Ph.D. Student
Emily HICKS
Ph.D. Student
Michaela HVIZDAK
Ph.D. Student
CU
Recent news
40th Mountain West SOT Meeting
On August 29-30, 2022, Michaela Hvizdak, the newest addition to the Lampe Lab, presented her researc…
22nd International Conference on Cytochrome P450
On July 17-21, 2022. The LAMPE Lab will present several of their research works in poster or talk fo…
EB – ASPET 2022
On April 02-05, 2022. Hannah Work & Emily Hicks will present their research work in posters.
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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
