Professor Theoharis Theoharides Professor of Pharmacology and Internal Medicine, Tufts University, Boston, USA Theoharis Theoharides is Professor of Pharmacology and Internal Medicine, as well as Director of Molecular Immunopharmacology and Drug Discovery, in the Department of Immunology at Tufts University School of Medicine, Boston, MA. He was born in Thessaloniki, Greece, and graduated with Honors from Anatolia College. He received all his degrees with Honors from Yale University, and was awarded the Dean’s Research Award and the Winternitz Prize in Pathology. He trained in internal medicine at New England Medical Center, which awarded him the Oliver Smith Award “recognizing excellence, compassion and service.” He also received a Certificate in Global Leadership from the Tufts Fletcher School of Law and Diplomacy and a Fellowship at the Harvard Kennedy School of Government. He has been serving as the Clinical Pharmacologist of the Massachusetts Drug Formulary Commission continuously since 1986. In Greece, he has served on the Supreme Advisory Health Councils of the Ministries of Health and of Social Welfare, as well as on the Board of Directors of the Institute of Pharmaceutical Research and Technology, and he is a member of the International Advisory Committee for the University of Cyprus School of Medicine. He first showed that mast cells, known for causing allergic reactions, are critical for inflammation, especially in the brain, and are involved in a number of inflammatory conditions that worsen by stress such as allergies, asthma, chronic fatigue syndrome, eczema, fibromyalgia, migraines, mastocytosis, multiple sclerosis, psoriasis, and most recently autism spectrum disorder. He has also shown that corticotropin-releasing hormone (CRH), neurotensin and substance P, peptides secreted under stress, act together, and with the cytokine IL-33, to trigger mast cells and microglia to secrete inflammatory molecules. These processes are inhibited Invest in ME research (Charity Nr. 1153730) by the novel flavonoids, luteolin and tetramethoxyluteolin that he has helped formulate in unique dietary supplements and a skin lotion. He has published over 400 scientific papers (JBC, JACI, JPET, NEJM, Nature, PNAS, Science) and 3 textbooks with 29,887 citations (h-factor 84) and he is in the top 5% of authors most cited in pharmacological and immunological journals. He has received 37 patents and trademarks, including three patents covering the use of luteolin in brain inflammation and autism: US 8,268,365 (09/18/12); US 9,050,275 (06/09/15); US 9,176,146 (11/03/15). Acting as Advisor, he was instrumental in the development of ibuprofen (Upjohn), Cetirizine (UCB) and Niaspan (Kos). He is also the Scientific Director of Algonot, LLC, as well as President of Theta Biomedical Consulting and Development Co., Inc., of BiomedAdvice, LLC, and of the nonprofit Brain-Gain.org. He is a member of 15 academies and scientific societies. He was inducted into the Alpha Omega Alpha National Medical Honor Society and the Rare Diseases Hall of Fame. At Tufts, he served on the Curriculum, Students Promotion, Grievance, Faculty Promotion and Tenure, as well as Strategic Planning Committees. He received the Tufts Excellence in Teaching ten times, the Tufts Distinguished Faculty Recognition Award twice, the Tufts Alumni Award for Faculty Excellence, Boston Mayor’s Community Award, and the Dr. George Papanicolau Award, as well as Honorary Doctor of Medicine from Athens University and Honorary Doctor of Sciences from Hellenic-American University. He is “Archon” of the Ecumenical Patriarchate of Constantinople. Abstract: Brain mast cell involvement in Myalgic Encephalopathy/Chronic Fatigue Syndrome Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) affects about 1-2% of the US population and is characterized by debilitating fatigue of six months in the absence of systemic diseases. Many ME/CFS patients also have fibromyalgia and skin hypersensitivity, which worsen with stress. We hypothesize that stimulation of mast cells (MC) in the hypotahalamus activate microglia leading to secretion of pro-inflammaotry mediators that disrupt normal homeostasis and advesrsely affect mitochondrial function. Corticotropin-releasing www.investinme.org Page 49 of 56

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