About

Professor Klarissa Jackson is a faculty member at the University of North Carolina at Chapel Hill in the Curriculum in Toxicology & Environmental Medicine. Her primary research focus is on drug and xenobiotic metabolism, mechanistic toxicology, and pharmacogenetics. She investigates how drugs and foreign chemical substances are metabolized in the body and the genetic factors that influence these processes. Her work aims to elucidate the mechanisms underlying toxicological responses to various compounds, contributing to a better understanding of individual variability in drug metabolism and toxicity. Professor Jackson's expertise in pharmacogenetics allows her to explore how genetic differences among individuals affect their susceptibility to toxicants and their responses to therapeutic drugs, which has important implications for personalized medicine and risk assessment in environmental health.

Research topics

• Medicine
• Pharmacology
• Biology
• Chemistry
• Biochemistry
• Internal medicine
• Bioinformatics
• Genetics
• Computational biology
• Cancer research

Selected publications

• Correction to “Interindividual Variability in Cytochrome P450 3A and 1A Activity Influences Sunitinib Metabolism and Bioactivation”

  Chemical Research in Toxicology · 2026-02-23

  articleSenior author
  PublisherDOI

• Impact of variation in CYP3A and CYP2C8 on tucatinib metabolic clearance in human liver microsomes

  Drug Metabolism and Disposition · 2025-03-10 · 3 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Elucidating Molecular Mechanisms of Drug-Induced Hepatotoxicity of Lapatinib

  Journal of Medicinal Chemistry · 2025-07-25 · 6 citations

  article

  DILI (drug-induced liver injury) remains a critical liability in drug discovery and development. However, there are few in vitro and preclinical models to predict DILI, and the knowledge of DILI molecular targets is even more limited. The lapatinib (1) prescription label carries a black box warning for idiosyncratic hepatotoxicity and this has prompted numerous studies aimed at understanding the underlying molecular mechanisms. Using lapatinib as a tool molecule, we first identified a novel P450 3A5-catalyzed bioactivation, leading to highly reactive quinone methide (QM) metabolites formed after ortho- and para-hydroxylation at the 3F-benzyl ring, followed by self-immolation. The structure and activity relationship (SAR) studies of lapatinib analogs characterized the positional substitute-dependent quinone methide formation. Proteomics data revealed that quinone methide formation through bioactivation followed by simultaneous covalent modifications/functional disruption of several cellular enzymes in mitochondrial energy-production and reduction of oxidative stress could lead to mitochondrial stress and overall hepatotoxicity.

  PublisherDOI

• Interindividual variability in imatinib metabolism in human liver microsomes and primary human hepatocytes: Impact of CYP2C8 and CYP3A phenotypes

  Drug Metabolism and Disposition · 2025-11-03

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Wellness in the invisible workforce: a pilot well-being study in black, indigenous, and people of color (BIPOC) women faculty in the pharmacy and pharmaceutical sciences

  UNC Libraries · 2025-05-15

  articleOpen access1st authorCorresponding
  PublisherDOI

• Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity

  Frontiers in Pharmacology · 2025-11-26

  articleOpen access

  Introduction Increased CYP3A-mediated drug clearance during pregnancy can lead to subtherapeutic dosing of CYP3A substrates. Pregnancy-related hormones (PRHs) increase CYP3A4 expression and activity in cultured human hepatocytes. However, the factors in maternal circulation that regulate pregnancy-mediated changes in CYP3A activity remain unclear. Methods This study investigated the association between maternal plasma concentrations of key steroidal PRHs and biomarkers of CYP3A activity in human pregnancy, and the impact of individual PRHs on CYP3A4 expression in primary human hepatocytes. Concentrations of estrone (E1), estradiol (E2), progesterone (P4), and cortisol (CRT), and 4 β -hydroxycholesterol (4 β -OH-CHO) and the 4 β -OH-CHO:CHO ratio (endogenous biomarkers of CYP3A activity), were quantified in human plasma across a spectrum of pregnancy states: healthy nonpregnant controls (n = 4), healthy pregnant volunteers (n = 6), and pregnant patients diagnosed with preeclampsia (n = 8). Results Plasma 4 β -OH-CHO concentrations (median [25%–75%]) were higher in healthy pregnant (141 [115, 165] ng/mL) and preeclampsia patients (129 [90.5, 191] ng/mL) compared to nonpregnant controls (69.8 [45.8, 82.5] ng/mL). In healthy pregnant and preeclampsia patients, plasma E1 ( r = 0.687, p = 0.007 ) and E2 ( r = 0.551, p = 0.041 ) concentrations positively correlated with plasma 4 β -OH-CHO concentrations. Conversely, no association between P4 ( r = 0.068, p = 0.817 ) or CRT ( r = -0.115, p = 0.696 ) concentrations and 4 β -OH-CHO were observed. Cultured human female primary hepatocytes were exogenously exposed in vitro to PRHs and absolute CYP protein concentrations were quantified. Consistent with the human plasma sample associations, E1 and E2 induced CYP3A4 mRNA and total CYP3A protein concentrations in a concentration-dependent manner. Discussion Altogether, these data suggest that increased concentrations of E1 and E2 contribute, at least in part, to increased hepatic CYP3A expression and activity during pregnancy in humans.

  PublisherOA PDFDOI

• Examining the Relationship between N4-Acetyl Sulfamethoxazole Metabolite Formation and NAT1/NAT2 Genotype in a Diverse Donor Cohort (Abstract ID: 157357)

  Journal of Pharmacology and Experimental Therapeutics · 2025-03-01

  articleSenior author
  PublisherDOI

• N-acetyltransferase (NAT) 1 and NAT2 enzyme activities drive interindividual variability in sulfamethoxazole N-acetylation

  Drug Metabolism and Disposition · 2025-11-01 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Wellness in the invisible workforce: a pilot well-being study in black, indigenous, and people of color (BIPOC) women faculty in the pharmacy and pharmaceutical sciences

  BMC Medical Education · 2025-05-08 · 1 citations

  articleOpen access

  BACKGROUND: Black, Indigenous, and other People of Color (BIPOC) women faculty are underrepresented in biomedical sciences and higher education. This disparity has been highlighted in previous studies to harm productivity, career progression, and well-being. This pilot study aimed to assess the perceived impact of a longitudinal well-being program for BIPOC women faculty, estimating its effects on well-being, burnout, and self-efficacy. METHODS: Full-time faculty in pharmacy or pharmaceutical science, identifying as BIPOC women, participated in this pilot repeated cross-sectional study of participants in a Well-Being Initiative, with the first cross-sectional study coming before a pilot intervention and the second cross-sectional coming after the pilot intervention. Cohort 1 engaged in a two-year program, while Cohort 2 participated for one year. Open-text questions assessed program impact on well-being, and inductive coding identified themes. Well-being, burnout, and self-efficacy were measured using the General Well-Being Index (WBI), Maslach Areas of Worklife Survey (AWS), 2-items from the Maslach Burnout Index-Human Services Survey (MBI-HSS), and General Self-Efficacy Survey (GSES). Descriptive statistics were calculated for primary and secondary outcomes. RESULTS: Sixteen participated in Cohort 1, and 18 participated in Cohort 2. Both cohorts reported a positive impact on well-being and a sense of community as a result of the program. Post-intervention median WBI decreased, and burnout and well-being risk declined (MBI: 24% and 28% point decrease at risk for burnout, WBI: median score 4 to 3 with 20% decreased risk for poor well-being, and median score 3 to 0.5 with a 61% point decrease at risk for poor well-being, for Cohorts 1 and 2, respectively). The AWS community subscale (Cohort 1) median score increased from 2.67 to 3.5, and values subscale (Cohort 2) median score increased 3.17 to 3.67, the largest increases. Cohort 2 exhibited improved self-efficacy (GSES median score change of 30 to 34). Participants reported the sense of community and connection built over the year(s) of the program, the ability to share of experiences from those further along in their career, having a safe space to be authentic with fellow participants, and the various sessions on creating self-care plans and maintaining core values as top themes of how program most benefited their well-being. Lessons learned and opportunities for improvement are addressed. CONCLUSION: Participants reported many of the key impacts were the program's ability to foster a sense of community and help them develop skills for personal and professional well-being. While higher baseline risks of poor well-being and burnout persist for BIPOC women faculty, positive trends emerged post-intervention. This study contributes to innovative strategies focused on supporting the well-being of BIPOC women faculty and lessons learned may inform and help refine future research. CLINICAL TRIAL NUMBER: Not applicable.

  PublisherOA PDFDOI

• Evaluating cannabidiol-induced liver injury with and without valproate using a three-dimensional human hepatocyte spheroid model

  Toxicology in Vitro · 2025-08-06 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Change of Grantee Institution: Role of Cytochrome P450 3A5 in the Metabolism and Hepatotoxicity of Lapatinib

  NIH · $659k · 2019–2020

• NIH Grant F31AG035483

  NIH · $31k · 2012

Frequent coauthors

• Arsany A. Abouda

  Lipscomb University

  22 shared

• Jessica L. Beers

  University of North Carolina at Chapel Hill

  18 shared

• Jennifer E. Bissada

  Lipscomb University

  17 shared

• Rachel D. Crouch

  Lipscomb University

  14 shared

• Kahari J. Wines

  University of Tennessee Health Science Center

  13 shared

• Jason D. Morrow

  The University of Texas Health Science Center at San Antonio

  12 shared

• Vivian Truong

  University of North Carolina at Chapel Hill

  10 shared

• Joseph Awad

  Vanderbilt University Medical Center

  10 shared

Labs

• Curriculum in Toxicology & Environmental MedicinePI

Education

• Ph.D., Pharmacology

  Vanderbilt University School of Medicine

  2011