Clinical Focus


  • Pediatric Hematology-Oncology

Academic Appointments


Professional Education


  • Medical Education: Stanford School of Medicine (1990) CA
  • Board Certification: American Board of Pediatrics, Hospice and Palliative Medicine (2010)
  • Board Certification: American Board of Pediatrics, General Pediatrics (1993)
  • Board Certification: American Board of Pediatrics, Pediatric Hematology-Oncology (1996)
  • Fellowship: Lucile Packard Children's Hospital (1996) CA
  • Medical Education: Stanford University (1990) CA
  • Residency: Lucile Packard Children's Hospital (1993) CA

2022-23 Courses


All Publications


  • Moral Distress Among Healthcare Professionals: Report of an Institution-Wide Survey JOURNAL OF NURSING SCHOLARSHIP Whitehead, P. B., Herbertson, R. K., Hamric, A. B., Epstein, E. G., Fisher, J. M. 2015; 47 (2): 117–25

    Abstract

    Moral distress is a phenomenon affecting many professionals across healthcare settings. Few studies have used a standard measure of moral distress to assess and compare differences among professions and settings.A descriptive, comparative design was used to study moral distress among all healthcare professionals and all settings at one large healthcare system in January 2011.Data were gathered via a web-based survey of demographics, the Moral Distress Scale-Revised (MDS-R), and a shortened version of Olson's Hospital Ethical Climate Scale (HECS-S).Five hundred ninety-two (592) clinicians completed usable surveys (22%). Moral distress was present in all professional groups. Nurses and other professionals involved in direct patient care had significantly higher moral distress than physicians (p = .001) and other indirect care professionals (p < .001). Moral distress was negatively correlated with ethical workplace climate (r = -0.516; p < .001). Watching patient care suffer due to lack of continuity and poor communication were the highest-ranked sources of moral distress for all professional groups, but the groups varied in other identified sources. Providers working in adult or intensive care unit (ICU) settings had higher levels of moral distress than did clinicians in pediatric or non-ICU settings (p < .001). Providers who left or considered leaving a position had significantly higher moral distress levels than those who never considered leaving (p < .001). Providers who had training in end-of-life care had higher average levels of moral distress than those without this training (p = .005).Although there may be differences in perspectives and experiences, moral distress is a common experience for clinicians, regardless of profession.Moral distress is associated with burnout and intention to leave a position. By understanding its root causes, interventions can be tailored to minimize moral distress with the ultimate goal of enhancing patient care, staff satisfaction, and retention.

    View details for DOI 10.1111/jnu.12115

    View details for Web of Science ID 000350981900003

    View details for PubMedID 25440758

  • ORGANIZATION AND FUNCTION OF A DIOXIN-RESPONSIVE ENHANCER JOURNAL OF BIOLOGICAL CHEMISTRY Fisher, J. M., Wu, L., Denison, M. S., Whitlock, J. P. 1990; 265 (17): 9676-9681

    Abstract

    The dioxin-responsive enhancer upstream of the CYP1A1 gene contains four copies of the recognition motif for the liganded Ah receptor. The results of deletion analyses, linker-scanning analyses, and the analysis of individual enhancer subdomains reveal that each copy of the motif contributes to the response of the enhancer to 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the context of the dioxin-responsive enhancer, a GC box, representing the DNA binding site for Sp1 (or a related transcription factor), has no detectable intrinsic activity but enhances gene expression when linked to a recognition motif for the liganded Ah receptor, thereby producing a synergistic effect on enhancer function.

    View details for Web of Science ID A1990DH14100020

    View details for PubMedID 2161840

  • PROTEIN-DNA INTERACTIONS AT RECOGNITION SITES FOR THE DIOXIN-AH RECEPTOR COMPLEX JOURNAL OF BIOLOGICAL CHEMISTRY Denison, M. S., Fisher, J. M., Whitlock, J. P. 1989; 264 (28): 16478-16482

    Abstract

    Gel retardation analyses reveal a cluster of six binding sites for the liganded Ah receptor within a 700-base pair DNA domain upstream of the mouse CYP1A1 gene. The nucleotide sequences of the binding sites define a consensus recognition motif for the liganded receptor. The consensus motif is not symmetric. Alteration of the consensus motif produces a decrease in the receptor-DNA interaction. The ligand receptor binds as a monomer to its recognition motif and preferentially binds to double-stranded DNA. These observations reveal apparent differences between 2,3,7,8-tetrachlorodibenzo-p-dioxin and steroid hormones in their respective mechanisms of action.

    View details for Web of Science ID A1989AR64100024

    View details for PubMedID 2550446

  • INDUCTION OF HEPATIC CYTOCHROME-P450 GENE-EXPRESSION BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN MOLECULAR BIOLOGY & MEDICINE Whitlock, J. P., Denison, M. S., Fisher, J. M., Shen, E. S. 1989; 6 (2): 169-178

    Abstract

    The halogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a persistent, widespread, potentially toxic environmental contaminant, which is a potent inducer of aryl hydrocarbon hydroxylase activity in the liver and other tissues. TCDD induces hydroxylase activity by increasing the rate of transcription of the CYP1A1 gene. Activation of CYP1A1 transcription requires the binding of TCDD to an intracellular protein, the Ah receptor, followed by the binding of the liganded receptor to a dioxin-responsive enhancer that is located upstream from the CYP1A1 gene. The liganded receptor recognizes a specific DNA sequence, which is present in multiple copies within the enhancer. The receptor-enhancer interaction occurs within the major groove of the DNA helix. DNA methylation in vitro interferes with the receptor-enhancer interaction and, therefore, has the potential to inhibit the biological response to TCDD.

    View details for Web of Science ID A1989CB47800010

    View details for PubMedID 2693891

  • REGULATION OF CYTOCHROME-P1-450 GENE-EXPRESSION IN MOUSE HEPATOMA-CELLS BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN DRUG METABOLISM REVIEWS Whitlock, J. P., Denison, M. S., Durrin, L. K., Fisher, J. M., GALEAZZI, D. R., Jones, P. B. 1989; 20 (2-4): 839-846

    View details for Web of Science ID A1989AV84800046

    View details for PubMedID 2806081

  • INDUCIBLE, RECEPTOR-DEPENDENT PROTEIN-DNA INTERACTIONS AT A DIOXIN-RESPONSIVE TRANSCRIPTIONAL ENHANCER PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Denison, M. S., Fisher, J. M., Whitlock, J. P. 1988; 85 (8): 2528-2532

    Abstract

    We have identified in mouse hepatoma cells a third cis-acting dioxin-responsive element (DRE) within the 5' flanking region of the cytochrome P1-450 gene, which is transcriptionally activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The DRE can activate a heterologous promoter and functions in either orientation; therefore, it has the properties of a transcriptional enhancer. The DRE fails to activate transcription in receptor-defective cells; therefore, it requires TCDD-receptor complexes for its function. By using a gel retardation assay, we show that nuclear extracts contain a protein that binds to the DRE in TCDD-inducible, receptor-dependent, and DNA sequence-specific fashion. The protein-DNA interaction occurs within 10 min of exposure of the cell to TCDD and does not require ongoing protein synthesis. Our results imply that the TCDD-receptor complex interacts specifically with the DRE and demonstrate a relationship between protein-DNA interaction in vitro and function in vivo. Our findings also suggest that the affinity of the TCDD-receptor complex for the DRE may be relatively high in comparison to analogous protein-DNA interactions at other inducible enhancers.

    View details for Web of Science ID A1988N023400024

    View details for PubMedID 2833743

  • 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN RECEPTORS REGULATE TRANSCRIPTION OF THE CYTOCHROME-P1-450 GENE JOURNAL OF CELLULAR BIOCHEMISTRY Durrin, L. K., Jones, P. B., Fisher, J. M., GALEAZZI, D. R., Whitlock, J. P. 1987; 35 (2): 153-160

    Abstract

    The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) dioxin, produces a diverse set of biological responses which, in some cases, reflects the altered expression of specific genes. An intracellular receptor protein binds TCDD saturably and with high affinity and mediates several of TCDD's biological effects. In mouse hepatoma cells, TCDD induces aryl hydrocarbon hydroxylase activity by activating the transcription of the cytochrome P1-450 gene. Studies of receptor-defective variant cells indicate that the activation of cytochrome P1-450 gene transcription requires functional TCDD receptors. Analysis of the DNA that flanks the 5'-end of the mouse cytochrome P1-450 gene reveals at least three control regions: a promoter, an inhibitory element, and a dioxin-responsive element (DRE). Therefore, expression of the cytochrome P1-450 gene represents a balance between negative and positive control. The DRE contains two discrete, non-overlapping DNA domains that respond to TCDD. Each TCDD-responsive domain acts independently of the other, each requires TCDD receptors for function, and each has the properties of a transcriptional enhancer. For example, the function of the DREs is relatively independent of both their location and their orientation with respect to the promoter. Together, the DREs and the TCDD-receptor complex constitute a dioxin-responsive enhancer system. Exposure of cells to TCDD results in the protection of a specific DNA domain from exonuclease digestion. This protection requires TCDD receptors. The protected domain maps to a DRE. This observation implies that the TCDD-receptor complex interacts with the DRE to activate the transcription of the cytochrome P1-450 gene.

    View details for Web of Science ID A1987K545100007

    View details for PubMedID 2828385