Sandra Sephton, PhD

Professor, Psychological and Brain Sciences

Senior Scientist, Games Graham Brown Cancer Center

Portrait of Sandra Sephton

 OFFICE Lutz Hall 442 & Life Sciences 322A

(502) 852-1166

sephton@louisville.edu

 LAB Lutz Hall 432/433/317/320a/320b

 (502) 852-2493 (wet lab)

Mindfulness & Biobehavioral Research Lab (Mindful Bio Lab) 

Highlights related to Research, Teaching, and Service

• Research experience: 25 years in salivary biometrics (diurnal salivary cortisol rhythms), 20 years in biobehavioral oncology, 19    years in mindfulness practice and research
• 17-years externally-funded research collaboration
• Over 70 peer-reviewed publications, >25% of which have been cited >100 times
• Overall works cited > 6000 times
• 17 prior extramural grants as PI, Co-I, or consultant
• Biomarker/wet lab expertise
• Translational research marked by active collaboration with local medical community
• Graduate and undergraduate neuroscience teaching experience
• Trained mindfulness instructor (undergoing certification)
• Fully developed hybrid (lecture + online) and fully-online course offerings
• Experienced mentor in undergraduate honors and clinical doctoral programs
• Faculty search and personnel committee experience
• Continuing service as ad hoc NIH grant reviewer for multiple study sections 
• Active planner/participant in professional organizations

Personal Statement

My first experience with stress research was as an undergrad at University of California, Davis: I worked for Dr. Gary Moberg in the Department of Animal Science. My job was to drive a large pickup truck with tall wooden sideboards in a somewhat erratic manner (easy for me). The bed was occupied with six or eight live sheep, who apparently found the experience stressful. When I got back to the “lab” (a barn), I had to flip them on to their backsides, hold their heads, and access the jugular vein for a blood sample. I took the tubes back to campus and donned a lead apron to run radio-immunoassays for cortisol and sex steroids. We found that stress caused reproductive failure, high cortisol, and low testosterone. Thus I learned about the balance of steroid pathways, and sheep, and became entranced with the notion that stress could so powerfully alter biology and health. A few more years of animal research paved the way for an epiphany that I actually enjoy humans, just as much. Hence, I studied positive psychological factors, mindfulness, and social support as factors that might ameliorate the impact of stress on human health. A tremendous postdoctoral opportunity yielded diurnal cortisol data from women with metastatic breast cancer, and we found that those with flattened diurnal cortisol rhythms suffered significantly earlier death. This data led me to explore connections between stress, circadian disruption and cancer progression. The journey thus far has provided expertise in diurnal salivary cortisol measurement, hormone assays in blood and urine, lymphocyte stimulation protocols, peripheral cytokine data, and actigraphic measurement of rest-activity and sleep-wake cycles. From subsequent studies in my lab and other labs, we learned that disrupted circadian and endocrine rhythms predict early mortality across a number of cancer types, and other diseases. Our data also point to hypotheses that mindfulness-based interventions, social support, and existential coping styles might preserve mental and physical function in the context of some stressful physical illnesses, including cancer. Current and future research will continue to explore circadian disruption as a mediator of psychosocial effects in cancer progression, and to describe the biological and health correlates of mindfulness meditation.

Education

  • University of California, Davis, B.S., 1985, Animal Science / Pre-Veterinary Medicine
  • Brigham Young University, M.S., 1989, Human Physiology & Anatomy
  • Brigham Young University, Ph.D., 1995, Behavioral Neuroscience
  • Stanford University, Post-doc, 1995-99, Fellowship in Psychoneuroimmunology and Biobehavioral Oncology

Research Interests

Mindfulness in clinical contexts  

One way to understand effects of stress on health is to examine factors that may ameliorate stress. Our group conducted a randomized controlled trial of an 8-week mindfulness-based stress-reduction (MBSR) program among 91 women with fibromyalgia. MBSR significantly reduced depression, sleep disturbance, and symptom severity; and gains were maintained at four months. MBSR did not significantly alter pain, physical functioning, or cortisol profiles. This research confirmed the efficacy of mindfulness meditation for clinical symptom reduction in a randomized controlled trial and refined scientific theory regarding mechanisms of mindfulness on clinical outcomes. 

Sephton, S.E., Salmon, P., Weissbecker, I., Ulmer, C., Floyd, A., Hoover, K. and Studts, J.L., 2007. Mindfulness meditation alleviates depressive symptoms in women with fibromyalgia: results of a randomized clinical trial. Arthritis Care & Research57(1), pp.77-85. PMID:17266067 https://doi.org/10.1002/art.22478

Cash, E., Salmon, P., Weissbecker, I., Rebholz, W.N., Bayley-Veloso, R., Zimmaro, L.A., Floyd, A., Dedert, E. and Sephton, S.E., 2015. Mindfulness meditation alleviates fibromyalgia symptoms in women: results of a randomized clinical trial. Annals of Behavioral Medicine49(3), pp.319-330. PMCID: PMC4802162 https://doi.org/10.1007/s12160-014-9665-0

We also completed observational research exploring ameliorative factors (dispositional mindfulness, sense of coherence, social support) with biomarkers, health and subjective wellness across a number of stressful circumstances. We found undergraduate students with high dispositional mindfulness had less academic stress and lower diurnal mean cortisol. In a three-month study of disaster evacuees, we found that social support and existential resources were associated with lower distress, and that ongoing anxiety was linked with flattened cortisol rhythms. 

Zimmaro, L.A., Salmon, P., Naidu, H., Rowe, J., Phillips, K., Rebholz, W.N., Giese-Davis, J., Cash, E., Dreeben, S., Bayley-Veloso, R.C., Jablonski, M., Hicks, A., Siwik, C., and Sephton, S.E. (2016) The Role of Dispositional Mindfulness in Stress and Health Outcomes in University Undergraduate Students. Mindfulness7(4), pp.874-885. https://doi.org/10.1007/s12671-016-0526-8

Thompson, D. J., Weissbecker, I., Cash, E., Simpson, D. M., Daup, M., Sephton, S.E. (2015). Stress and cortisol in disaster evacuees: an exploratory study on associations with social protective factors. Applied Psychophysiology and Biofeedback40(1): 33-44. PMID: 25787070  https://doi.org/10.1007/s10484-015-9270-4

Circadian disruption and cancer progression

Clinical prospective studies have clearly demonstrated the prognostic value of circadian rhythms in human cancers including breast (Sephton et al., 2000), lung (Sephton et al., 2015), colorectal, renal, and gynecologic cancer; contributing to the evidence that circadian disruption accelerates tumor progression. I have worked to understand the prognostic value of circadian disruption in cancer survival, exploring how circadian regulation protects against tumor progression and promotes quality of life. Patient distress, depressive symptoms and other cancer comorbidities are linked with more marked circadian disruption. Major coordinators of central clock control over the timing of peripheral cell activities include the stress hormone, cortisol. 

Sephton, S. E., Sapolsky, R. M., Kraemer, H. C., & Spiegel, D. (2000). Diurnal cortisol rhythm as a predictor of breast cancer survival. Journal of the National Cancer Institute92(12), 994-1000. https://doi.org/10.1093/jnci/92.12.994

Antoni, M. H., Lutgendorf, S. K., Cole, S. W., Dhabhar, F. S., Sephton, S. E., McDonald, P. G., ... & Sood, A. K. (2006). The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nature Reviews Cancer6(3), 240. 

Sephton, S.E., Cash (née Lush), E., Dedert, E.A., Floyd, A.R., Rebholz, W.N., Dhabhar, F.S., Spiegel, D. and Salmon, P., 2013. Diurnal cortisol rhythm as a predictor of lung cancer survival. Brain, behavior, and immunity, 30, pp.S163-S170. PMID: 22884416 https://doi.org/10.1016/j.bbi.2012.07.019

Eismann, E.A., Cash (née Lush), E. and Sephton, S.E., 2010. Circadian effects in cancer-relevant psychoneuroendocrine and immune pathways. Psychoneuroendocrinology, 35(7), pp.963-976. PMID: 20097011  https://doi.org/10.1016/j.psyneuen.2009.12.011

In support of the notion that circadian regulation and cancer progression are linked, our research group demonstrated that presurgical breast cancer patients with strong circadian activity rhythms have lower levels of peripheral blood biomarkers that are suggestive of tumor invasion/immunosuppression (e.g., VEGF).

Cash, E., Sephton, S.E., Chagpar, A.B., Spiegel, D., Rebholz, W.N., Zimmaro, L.A., Tillie, J.M. and Dhabhar, F.S., 2015. Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery. Brain, behavior, and immunity, 48, pp.102-114. PMID: 25728235 https://doi.org/10.1016/j.bbi.2015.02.017

Mechanisms by which circadian disruption accelerates tumor progression, and interaction with psychosocial factors (e.g., distress, coping) 

That diurnal cortisol disruption predicts early cancer mortality begs another question: Is circadian dysregulation limited to endocrine systems, or is it systemic? We explored that association of central rhythm dysregulation with peripheral cortisol rhythms in breast cancer patients awaiting surgery. Those with flattened diurnal cortisol rhythms had more inconsistent circadian cycles of activity versus restful behavior (Dedert et al., 2012). In addition, cancer patients who reported high distress, or who used more avoidant as opposed to problem-focused coping styles, had significantly more daytime sedentary behavior and higher evening cortisol. Our data suggest the major driver of poor outcomes was distress rather than physiological disruption. Our findings suggest it may take extended time for physiological dysregulation and associated comorbidities to develop over the course of cancer and its treatment.

Dedert, E., Cash (née Lush), E., Chagpar, A., Dhabhar, F.S., Segerstrom, S.C., Spiegel, D., Dayyat, E., Daup, M., McMasters, K. and Sephton, S.E., 2012. Stress, coping, and circadian disruption among women awaiting breast cancer surgery. Annals of behavioral medicine44(1), pp.10-20. PMID: 22450856  https://doi.org/10.1007/s12160-012-9352-y

Siwik, C., Hicks, A., Phillips, K., Rebholz, W.N., Zimmaro, L.A., Weissbecker, I., Cash, E., Sephton, S.E. (In press). Impact of Coping Strategies on Perceived Stress, Depression, and Cortisol Profiles Among Gynecologic Cancer Patients. Journal of Health Psychology. PMID: 29172807 https://doi.org/10.1177/1359105317740737

Rebholz, W.N., Cash, E., Zimmaro, L.A., Bayley-Veloso, R., Phillips, K., Siwik, C., Chagpar, A.B., Dhabhar, F.S., Spiegel, D., Bell, B.S. and Sephton, S.E., 2016. Distress and quality of life in an ethnically diverse sample awaiting breast cancer surgery. Journal of health psychology, p.1359105316659916. PMID: 27466289  https://doi.org/10.1177/1359105316659916

Pathways that may explain associations of depression with cancer survival

Depression has long been associated with marked circadian disruption including flattening and elevation of the diurnal cortisol rhythm. Psychological symptoms are associated with physiological mediators known to modulate central circadian rhythms (e.g., inflammatory cytokines). Thus, the well-demonstrated prognostic value of depression for shorter cancer survival is a second, related area of research focus. Recent work with PI Dr. Liz Cash confirms our ability to produce data from patients with head and neck cancer. We recently demonstrated the prognostic value of depressive symptoms in this cancer type.

Zimmaro, L., Sephton, S.E., Siwik, C.; Phillips, K.; Rebholz, W.; Kraemer, H.; Giese-Davis, J.; Wilson, L.; Bumpous, J.; Cash, E. 2018 Depressive Symptoms Predict Head and Neck Cancer Survival: Examining Plausible Behavioral and Biological Pathways. Cancer, 124(5), 1053-1060. PMCID: PMC5821545 https://doi.org/10.1002/cncr.31109

In work from my lab as well as that of Dr. Susan Lutgendorf, we’ve explored psychological correlates and biomarkers of depression in cancer patients---with the intent of understanding pathways that may mediate effects of depression on tumor progression.

Sephton, S.E., Dhabhar, F.S., Keuroghlian, A.S., Giese-Davis, J., McEwen, B.S., Ionan, A.C. and Spiegel, D., 2009. Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer. Brain, behavior, and immunity23(8), pp.1148-1155. PMID: 19643176  https://doi.org/10.1016/j.bbi.2009.07.007

Weinrib, A.Z., Sephton, S.E., DeGeest, K., Penedo, F., Bender, D., Zimmerman, B., Kirschbaum, C., Sood, A.K., Lubaroff, D.M. and Lutgendorf, S.K., 2010. Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer. Cancer116(18), pp.4410-4419. PMCID: PMC3118555  doi: 10.1200/JCO.2007.14.1978

Lutgendorf, S.K., Weinrib, A.Z., Penedo, F., Russell, D., DeGeest, K., Costanzo, E.S., Henderson, P.J., Sephton, S.E., Rohleder, N., Lucci III, J.A. and Cole, S., 2008. Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. Journal of Clinical Oncology26(29), pp.4820-4827. PMCID: PMC2653140  doi: 10.1200/JCO.2007.14.1978

Advancing methods by which diurnal salivary cortisol profiles are measured and analyzed and deepening understanding of neurobiological correlates

Human biomarkers research is complicated by many factors in measurement, data cleaning and analyses. I’ve focused efforts on refining state-of-the-art measures of circadian and endocrine function in home-based, naturalistic environments that are real-world relevant. A long-term collaboration with coinvestigator Suzanne Segerstrom has produced work that informs research design to enhance the reliability of measurement of salivary cortisol.

Segerstrom, S.C., Sephton, S.E. and Westgate, P.M., 2017. Intraindividual variability in cortisol: Approaches, illustrations, and recommendations. Psychoneuroendocrinology78, pp.114-124. PMCID: PMC5362320  https://doi.org/10.1016/j.psyneuen.2017.01.026

Segerstrom, S.C., Boggero, I.A., Smith, G.T. and Sephton,S.E., 2014. Variability and reliability of diurnal cortisol in younger and older adults: implications for design decisions. Psychoneuroendocrinology49, pp.299-309. PMCID: PMC4165809 https://doi.org/10.1016/j.psyneuen.2014.07.022

I’ve also focused on neurological and cognitive correlates of diurnal cortisol patterns in both collaborative research and in work from my own lab. I provided cortisol analyses for neuroimaging collaborators, and data showed estimates of cortical but not hippocampal or amygdala volume were associated with evening basal salivary cortisol and cortisol reactivity, and these effects were moderated by PTSD. 

Babson, K.A., Woodward, S.H., Schaer, M., Sephton, S.E. and Kaloupek, D.G., 2017. Salivary Cortisol and Regional Brain Volumes Among Veterans With and Without Posttraumatic Stress Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging2(4), pp.372-379. 

In both recent work with long-time collaborator Dr. Suzanne Segerstrom and work from my laboratory, we found cortisol exposure to be associated with memory dysfunction.

Segerstrom, S.C., Geiger, P.J., Boggero, I.A., Schmitt, F.A. and Sephton, S.E. (2016). Endogenous cortisol exposure and declarative verbal memory: A longitudinal study of healthy older adults. Psychosomatic medicine78(2), p.182. PMCID: PMC4738083  https://doi.org/10.1016/j.bpsc.2016.11.007

Complete List of Peer Reviewed Journal Articles

https://www.ncbi.nlm.nih.gov/sites/myncbi/1BWow6sB96e5D/bibliography/53579980/public/?sort=date&direction=descending

Courses Often Taught

  • PSYC 305 - Brain & Behavior
  • PSYC 355 - Neuroscience
  • PSYC 491-496 Independent Research
  • PSYC 687 - Cultural Neuroscience
  • Koru Basic Mindfulness, Koru Mindfulness 2.0

Selected Awards and Honors

2014 -2019        Student Mentor for NIH (National Cancer Institute) 1R25CA134283-01A2 (Hein, D.): U of L Cancer Education Program.

2014                  Grant Reviewer for the Canadian Cancer Society Research Institute.

2014-15             Grant Reviewer, National Institutes of Health Behavioral Medicine: Interventions and Outcomes Study Section.

2014-16             Grant Reviewer, National Institutes of Health Mechanisms of Emotion, tress and Health Study Section.

2017 – 2018      Senior Scientist, James Graham Brown Cancer Center

2017-2018         Principal Investigator, inaugural award of the Jesse H. Wright, M.D., Ph.D. Endowment for Mood Disorders Research. 

2018                  Recipient, College of Arts & Sciences Outstanding Mentorship Award

2018-19             Grant Reviewer, National Institutes of Health Mechanisms of Emotion, Stress and Health Study Section (June 2018, February 2019).