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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

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.

Coronavirus SARS-CoV-2
Development of modular protease inhibitors for SARS-CoV-2 infection

The Covid-19 pandemic has unsettled daily life and impacted the global economy, but viruses like SARS-CoV-2 will also continue to threaten human society in the future. Mutations in the viral genome lead to new viral propagation waves and also new health restrictions. Vaccination may mitigate the total number of people infected but will not provide treatment for those already infected. Targeting the main protease of SARS-CoV-2 using a modular inhibitor approach is our proposed strategy to inhibit new viral variants and circumvent potential viral drug resistance. We are currently exploring the potential of SARS-CoV-2 protease inhibitors in collaboration with the Reigan laboratory.

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Recent publications

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 and neonate. In addition to its role metabolizing retinoic acid and the endogenous steroid dehydroep…

Inhibition of CYP3A7 DHEA-S Oxidation by Lopinavir and Ritonavir: An Alternative Mechanism for Adrenal Impairment in HIV Antiretroviral-Treated Neonates

Prophylactic antiretroviral therapy (ART) in HIV infected pregnant mothers and their newborns can dramatically reduce mother-to-child viral transmission and seroconversion in the neonate. The ritonavi…

Neonatal cytochrome P450 CYP3A7: A comprehensive review of its role in development, disease, and xenobiotic metabolism

The human cytochrome P450 CYP3A7, once thought to be an enzyme exclusive to fetal livers, has more recently been identified in neonates and developing infants as old as 24 months post-gestational age.…

Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry

The lanthanides (Ln3+), or rare earth elements, have proven to be useful tools for biomolecular NMR, X-ray crystallographic, and fluorescence analyses due to their unique 4f orbitals. However, their u…

Ligand-dependent modulation of hOCT1 transport reveals discrete ligand binding sites within the substrate translocation channel

The human hepatic organic cation transporter 1 (hOCT1) is a well-known transporter of both xenobiotic and endogenous cations. The substrates and inhibitors of hOCT1 are structurally and physiochemical…

Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7

The metabolism of testosterone to 6β-hydroxytestosterone (6β-OH-T) is a commonly used assay to evaluate human CYP3A enzyme activities. However, previous reports have indicated that CYP3A7 also produce…

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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

Professional Research Associate

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Lab events

Christmas lab lunch at Chook

Lampe lab BBQ

Lab hike at Mount Sanitas, Boulder

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Recent news

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 format.

EB – ASPET 2022

On April 02-05, 2022. Hannah Work & Emily Hicks will present their research work in posters.

PharmD-2021

On September 20-22, 2021. Dr. LAMPE will present our research on drug metabolism in neonates.

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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

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