OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)

OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Thaddeus W. Pace eRA COMMONS USER NAME (agency login): TWWPACE POSITION TITLE: Assistant Professor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) INSTITUTION AND LOCATION DEGREE Completion Date FIELD OF STUDY (if applicable) MM/YYYY Albright College, Reading, PA BS 05/1998 Psychobiology University of Colorado at Boulder, Boulder, CO MA 08/2000 Psychology University of Colorado at Boulder, Boulder, CO PHD 06/2004 Neuroscience/ Psychology Emory University, Atlanta, GA Postdoctoral Fellow 06/2006 Human Stress Immunology

A. Personal Statement I am a biological psychologist with a primary interest in translational mind-body science in the context of stress, illness, and wellness. A major focus of my work today is the biology of wellness in cancer survivors, particularly women who have experienced breast cancer. I am especially interested in the development of novel intervention programs that target mind-body biological pathways, including endocrine and inflammatory immune systems. I have 11+ years of experience measuring markers of the stress response, including key inflammatory biomarkers (e.g. interleukin-6 and nuclear factor-κB), and 7 years of experience with effectiveness research for different meditation programs. Besides the development of compassion meditation for breast cancer survivors, I am also keenly interested in the potential of natural products to reverse inflammation-associated fatigue experienced by breast cancer survivors. My research is supported by several NIH grants, including an R21 from NCI to explore the effectiveness of curcumin to attenuate inflammation and fatigue in survivors of breast cancer.

1. Smith AK, Conneely KN, Pace TW, Mister D, Felger JC, Kilaru V, Akel MJ, Vertino PM, Miller AH, Torres MA. Epigenetic changes associated with inflammation in breast cancer patients treated with chemotherapy. Brain Behav Immun. 2014 May;38:227-36. PubMed PMID: 24583204; PubMed Central PMCID: PMC4312666. 2. Torres MA, Pace TW, Liu T, Felger JC, Mister D, Doho GH, Kohn JN, Barsevick AM, Long Q, Miller AH. Predictors of depression in breast cancer patients treated with radiation: role of prior chemotherapy and nuclear factor kappa B. Cancer. 2013 Jun 1;119(11):1951-9. PubMed PMID: 23512358; PubMed Central PMCID: PMC3663885. 3. Olivera A, Moore TW, Hu F, Brown AP, Sun A, Liotta DC, Snyder JP, Yoon Y, Shim H, Marcus AI, Miller AH, Pace TW. Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2- pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties. Int Immunopharmacol. 2012 Feb;12(2):368-77. PubMed PMID: 22197802; PubMed Central PMCID: PMC3372981. 4. Pace TW, Negi LT, Adame DD, Cole SP, Sivilli TI, Brown TD, Issa MJ, Raison CL. Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress. Psychoneuroendocrinology. 2009 Jan;34(1):87-98. PubMed PMID: 18835662; PubMed Central PMCID: PMC2695992.

B. Positions and Honors Positions and Employment 2006 - 2006 Adjunct Instructor, Spelman College, Department of Psychology, Atlanta, GA

2006 - 2012 Assistant Professor, Emory University, Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA 2007 - 2013 Member, Emory University, Emory Winship Cancer Institute, Atlanta, GA 2007 - 2013 Neuroscience Faculty, Emory University, Division of Biological and Biomedical Sciences, Atlanta, GA 2013 - Assistant Professor, University of Arizona, College of Nursing, Tucson, AZ 2013 - Assistant Professor, University of Arizona, Department of Psychiatry, Tucson, AZ 2013 - Member, University of Arizona, Arizona Cancer Center, Tucson, AZ Other Experience and Professional Memberships 2005 - Member, Psychoneuroimmunology Research Society 2005 - Member, American Association for the Advancement of Science 2010 - Member, American Psychological Association 2011 - Member, American Psychosomatic Society Honors 1998 Psychobiology Award, Albright College 2006 Travel Award, Psychoneuroimmunology Research Society 2008 Professional Development Award, President's Commission for LGBT Concerns, Emory University 2012 Fellow, Poptech Science 2014 40 under 40 Honoree, Tucson Hispanic Chamber of Commerce and the Arizona Daily Star

C. Contribution to Science 1. Symptoms and inflammation in breast cancer survivors.

While at the Winship Cancer Institute at Emory I was fortunate to start a partnership with Mylin Torres, MD, a radiation oncologist. Together we conducted studies on the association between inflammation and major symptoms experienced by women diagnosed with breast cancer who had recently entered survivorship. In agreement with prior work by others, we found that fatigue and depression are increased in women after treatment for breast cancer, especially in those who had received combined radiation and chemotherapy. We also found that these symptoms, especially fatigue, are associated with NF-κB activity in circulating immune cells. Increased inflammation may be the result of chemotherapy-induced changes in gene methylation. Based on findings around the link between NF-κB and fatigue, Dr. Torres and I are currently conducting an NCI-funded trial on the effectiveness of a novel botanical, curcumin, to reduce inflammation and improve fatigue in women after treatment for breast cancer (see Current Research Support below). We predict that Meriva (a special formulation of curcumin) will reduce both NF-κB activity and major symptoms experienced by survivors.

a. Torres MA, Pace TW, Liu T, Felger JC, Mister D, Doho GH, Kohn JN, Barsevick AM, Long Q, Miller AH. Predictors of depression in breast cancer patients treated with radiation: role of prior chemotherapy and nuclear factor kappa B. Cancer. 2013 Jun 1;119(11):1951-9. PubMed PMID: 23512358; PubMed Central PMCID: PMC3663885. b. Smith AK, Conneely KN, Pace TW, Mister D, Felger JC, Kilaru V, Akel MJ, Vertino PM, Miller AH, Torres MA. Epigenetic changes associated with inflammation in breast cancer patients treated with chemotherapy. Brain Behav Immun. 2014 May;38:227-36. PubMed PMID: 24583204; PubMed Central PMCID: PMC4312666.

2. Botanicals that target inflammation to ameliorate symptoms experienced by breast cancer survivors.

Based on my early findings around inflammation and symptoms experienced by cancer survivors, in 2009 I began studies on the effectiveness of novel botanical compounds (as well as synthetic analogs) that act as anti-inflammatory agents to positively impact mood and behavior. These efforts started with curcumin as well as UBS109, a synthetic curcuminoid. Efforts began with a mouse model of cytokine-induced behavioral change and have now moved into breast cancer survivors. I am PI of an ongoing, 2-year trial to test the effectiveness of a formulation of curcumin (Meriva) to reduce NF-κB activation and ameliorate fatigue in breast cancer survivors. a. Olivera A, Moore TW, Hu F, Brown AP, Sun A, Liotta DC, Snyder JP, Yoon Y, Shim H, Marcus AI, Miller AH, Pace TW. Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2- pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties. Int Immunopharmacol. 2012 Feb;12(2):368-77. PubMed PMID: 22197802; PubMed Central PMCID: PMC3372981.

3. Mechanisms of compassion meditation.

My work on the inflammatory response to stress in patients with depression and early life maltreatment lead me to collaborate with Charles Raison, MD, a psychiatrist, and Dr. Satya Dev Negi, a former Tibetan Buddhist monk turned Tibetan Buddhist scholar. In 2006 Drs. Negi and Raison were working together to create a multi-week meditation intervention program called Cognitively-Based Compassion training (CBCT), based on the ancient Tibetan Buddhist meditation tradition known as lojong. Modeled on Mindfulness Based Stress Reduction, CBCT follows an iterative, 8-week manualized progression that works to build self-compassion, emotional intelligence, and empathy. Shortly after its manualization, Drs. Raison, Negi and I assessed the effects of CBCT on stress-induced markers of inflammation in you adults. We found that those who learned and practiced CBCT exhibited reduced stress-associated markers of inflammation (IL-6). Subsequent studies have revealed that CBCT also changes activity in key brain regions associated with emotion and empathy, including the dorsomedial prefrontal cortex. We believe that CBCT offers unique and exciting potential to positively impact symptoms experienced by breast cancer survivors given the involvement of changes in inflammation, self-compassion, and feelings of connectedness experienced by these women.

a. Pace TW, Negi LT, Adame DD, Cole SP, Sivilli TI, Brown TD, Issa MJ, Raison CL. Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress. Psychoneuroendocrinology. 2009 Jan;34(1):87-98. PubMed PMID: 18835662; PubMed Central PMCID: PMC2695992. b. Pace TW, Negi LT, Sivilli TI, Issa MJ, Cole SP, Adame DD, Raison CL. Innate immune, neuroendocrine and behavioral responses to psychosocial stress do not predict subsequent compassion meditation practice time. Psychoneuroendocrinology. 2010 Feb;35(2):310-5. PubMed PMID: 19615827; PubMed Central PMCID: PMC3083925. c. Desbordes G, Negi LT, Pace TW, Wallace BA, Raison CL, Schwartz EL. Effects of mindful- attention and compassion meditation training on amygdala response to emotional stimuli in an ordinary, non-meditative state. Front Hum Neurosci. 2012;6:292. PubMed PMID: 23125828; PubMed Central PMCID: PMC3485650. d. Pace TW, Negi LT, Dodson-Lavelle B, Ozawa-de Silva B, Reddy SD, Cole SP, Danese A, Craighead LW, Raison CL. Engagement with Cognitively-Based Compassion Training is associated with reduced salivary C-reactive protein from before to after training in foster care program adolescents. Psychoneuroendocrinology. 2013 Feb;38(2):294-9. PubMed PMID: 22762896.

4. Illness, inflammation, and psychological stress.

A central theme of my work has always been the body's physiological response to stress. Starting as a postdoctoral fellow and then as junior faculty at Emory, I explored how the endocrine and inflammatory immune responses to stress were different in people currently experiencing major depression with a history of early life maltreatment. These studies, published in the American Journal of Psychiatry, revealed that inflammatory immune responding to psychological stress (measured either as circulating concentrations of inflammatory biomarker, interleukin (IL)-6, or as immune cell nuclear factor-κB [NF-κB] activity) is exaggerated in depressed patients. This seminal study introduced the provocative idea that stress-induced inflammation may be a critical driver to the development and ongoing severity of depression and other stress-related psychiatric conditions. This study has been cited numerous times and has served as the foundation of multiple follow up efforts by my group and others. A subsequent study of mine demonstrated that NF-κB activity is also increased in patients experiencing another stress-related psychiatric illness, posttraumatic stress disorder. Together, these studies contribute in significant ways to the theory that stress-associated inflammation drives the risk and severity of illness. a. Pace TW, Mletzko TC, Alagbe O, Musselman DL, Nemeroff CB, Miller AH, Heim CM. Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry. 2006 Sep;163(9):1630-3. PubMed PMID: 16946190. b. Pace TW, Miller AH. Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Ann N Y Acad Sci. 2009 Oct;1179:86-105. PubMed PMID: 19906234; PubMed Central PMCID: PMC3399249. c. Pace TW, Heim CM. A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities. Brain Behav Immun. 2011 Jan;25(1):6-13. PubMed PMID: 20934505. d. Pace TW, Wingenfeld K, Schmidt I, Meinlschmidt G, Hellhammer DH, Heim CM. Increased peripheral NF-κB pathway activity in women with childhood abuse-related posttraumatic stress disorder. Brain Behav Immun. 2012 Jan;26(1):13-7. PubMed PMID: 21801830.

Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/thaddeus.pace.1/bibliography/41164223/public/? sort=date&direction=ascending

D. Research Support Ongoing 5R21 CA178603-02 (Pace, PI) 09/15/14-08/31/16 NIH/NCI Meriva for Treatment-Induced Inflammation and Fatigue in Women with Breast Cancer This pilot study is determining the effectiveness of Meriva, a unique formulation of the natural product curcumin, to decrease inflammation and fatigue in women after radiotherapy and chemotherapy for breast cancer. Inflammatory activation as a result of treatment for breast cancer has been associated with long-term fatigue in breast cancer survivors. Although curcumin has been found to exert power anti-inflammatory actions at a number of levels (including NF-kB, a lynchpin of the inflammatory signaling cascade), concern exists about absorption of curcumin. Meriva is a unique formulation that has been shown to enhance blood levels of curcumin. Role: PI

5R01 MH099211-03 (Gillespie, PI) 04/24/13-02/28/18 NIH/NIMH Stress-Related Psychobiology and Inflammation in Diabetic African-American Women Low socioeconomic status is strongly associated with exposure to traumatic events and elevated rates of psychiatric illness, including post-traumatic stress disorder PTSD and major depressive disorder. These psychiatric illnesses are predictive of increased risk for cardiovascular disease and metabolic disorders. Studies proposed in this application will enhance our understanding of the biological mechanisms linking trauma-related psychiatric illness to medical illness. Role: Co-Investigator

5R34 AT007837-03 (Funk, PI) 09/01/13-08/31/16 NIH/NCCIH Curcuma longa L. in Rheumatoid Arthritis (CLaRA): Clinical Planning Study This project is conducting a randomized controlled trial of two doses of a commercial curcuminoid formulation Meriva for the treatment of rheumatoid arthritis (RA) patients who have failed to respond to methotrexate (MTX) treatment. This could overcome the challenge of RA treatment with MTX and address the concern of low bioavailability in utilizing curcuminoids for health maintenance or disease. The study could also collect important information needed for a larger efficacy trial. Role: Co-Investigator

Completed 5R21 CA155511-02 (Torres, PI) 07/01511-06/30/14 NIH/NCI Racial Disparities in Radiation-Induced Cutaneous Toxicity and Fatigue in Patients with Breast Cancer This study is designed to determine the relationship between radiation-induced cutaneous toxicity and fatigue in African American versus Caucasian women with breast cancer. A special emphasis is placed on the potential role of inflammation as a mediating mechanism. Role: Co-Investigator