Dr. John D. Baxter, world renowned scientist and medical visionary, famous for cloning of the first human growth hormone gene, passed away Wednesday, October 5, 2011, after an intensive 2-month battle with a rare form of cancer. He was 71.
Dr. Baxter was an inspirational leader in metabolic research and medicine, and a highly respected and valued member of The Methodist Hospital community. He was a senior member of The Methodist Hospital Research Institute, director of the Genomic Medicine research program, co-director of the Methodist Diabetes and Metabolism Institute, and chief of the Division of Endocrinology for The Methodist Hospital.
“We will miss an extraordinary intellect, truly one of the most accomplished and inspirational scientists in all of science,” says Mauro Ferrari, President and CEO of The Methodist Hospital Research Institute, “I trust that the very lights John has lit will bring warmth, hope, and a new, luminous future to humankind.”
John D. Baxter, M.D.
B.A. University of Kentucky, Lexington, KY (Chemistry)
Internship, Department of Internal Medicine, Yale New Haven Hospital, New Haven, CT.
After completing his postdoctoral training in 1972, Dr. Baxter joined the UCSF faculty in the Departments of Medicine and Biochemistry and Biophysics. He remained at UCSF for 36 years, becoming full Professor of Medicine in 1979 and serving in numerous leadership posts, including Director of the Endocrine Research Division, Director of the Metabolic Research Unit and Chief of the Division of Endocrinology at the Parnassus and Mt. Zion campuses.
Dr. Baxter has made several landmark scientific contributions. He cloned the growth hormone family of genes, including the first human hormone gene. He was also instrumental in demonstrating the possibility that mammalian proteins, including growth hormone could be produced in bacteria. He was the first to discover a hormone receptor defect that caused hormone resistance and the numerous diseases that result from this condition, and the atomic structure of a small molecule liganded to a nuclear receptor domain. He is currently developing and examining compounds to treat obesity, atherosclerosis, and diabetes, and using molecular and structural biology to examine the primary mechanisms of thyroid hormone receptor action.
Dr. Baxter has published over 200 papers in peer-reviewed journals; has started five companies in the biotechnology and other medical industries with market capitalizations, depending on time of assessment, worth over $4 billion; is the inventor or principal scientist on several patents that have yielded over $350 million in royalties to UCSF; is a past President of the Endocrine Society; and is a member of the National Academy of Sciences and the Institute of Medicine of the National Academy of Sciences. His awards include the highest honors (Koch Award) from The Endocrine Society and the American Thyroid Association (Ingbar Award), and the Outstanding Investigator Award from the Howard Hughes Medical Institute. Around 30 of his trainees have attained full professorships, including either in the UC system and two that have been elected to the National Academy of Sciences. A number of others have been successful in industry. Dr. Baxter assumed his positions at the Methodist Hospital Research Institute in 2008.
Current studies in Dr. Baxter's laboratory focus on nuclear receptors including the thyroid hormone receptor (TR). His group is developing and studying the mechanism of action of selective TR binding analogs that specifically elicit beneficial effects on dyslipidemia, body weight and fatty liver disease, in the absence of effects on heart, bone and muscle. These compounds should represent novel treatments for obesity, hyperlipidemia, atherosclerosis, diabetes and fatty liver disease. Dr. Baxter's team is also investigating mechanisms of thyroid hormone action. These include studies of metabolic parameters and actions of TRs +/- thyroid hormone at the DNA and gene expression levels.
Obesity, atherosclerosis, diabetes, fatty liver thyroid hormone action, nuclear receptors, DNA binding, gene expression.
Yuan C, Lin JZ, Sieglaff DH, Ayers SD, Denoto-Reynolds F, Baxter JD, Webb P. Identical Gene Regulation Patterns of T3 and Selective Thyroid Hormone Receptor Modulator GC-1. Endocrinology. 2011 Nov 8.
Deng T, Sieglaff DH, Zhang A, Lyon CJ, Ayers SD, Cvoro A, Gupte AA, Xia X, Baxter JD, Webb P, Hsueh WA.A peroxisome proliferator-activated receptor gamma (PPARgamma)/PPARgamma coactivator 1beta autoregulatory loop in adipocyte mitochondrial function. Biol Chem. 2011 Sep 2;286(35):30723-31.
Figueira AC, Saidemberg DM, Souza PC, Martínez L, Scanlan TS, Baxter JD, Skaf MS, Palma MS, Webb P, Polikarpov I. Analysis of agonist and antagonist effects on thyroid hormone receptor conformation by hydrogen/deuterium exchange. Mol Endocrinol. 2011 Jan;25(1):15-31.
Gupte AA, Liu JZ, Ren Y, Minze LJ, Wiles JR, Collins AR, Lyon CJ, Pratico D, Finegold MJ, Wong ST, Webb P, Baxter JD, Moore DD, Hsueh WA. Rosiglitazone attenuates age- and diet-associated nonalcoholic steatohepatitis in male low-density lipoprotein receptor knockout mice. Hepatology. 2010 Dec;52(6):2001-11.
Ladenson PW, Kristensen JD, Ridgway EC, Olsson AG, Carlsson B, Klein I, Baxter JD, Angelin B. Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med. 2010 Mar 11;362(10):906-16.
Baxter JD, Webb P. Thyroid hormone mimetics: potential applications in atherosclerosis, obesity and type 2 diabetes. Nat Rev Drug Discov. 2009 8(4):308-20 (2009)
Martínez L, Nascimento AS, Nunes FM, Phillips K, Aparicio R, Dias SM, Figueira AC, Lin JH, Nguyen P, Apriletti JW, Neves FA, Baxter JD, Webb P, Skaf MS, Polikarpov I. Gaining ligand selectivity in thyroid hormone receptors via entropy. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20717-22.
Identification of CCR4 and other essential thyroid hormone receptor co-activators by modified yeast synthetic genetic array analysis. Govindan M, Meng X, Denis CL, Webb P, Baxter JD, Walfish PG. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19854-9
Berkenstam A, Kristensen J, Mellstrom K, Carlsson B, Malm J, Rehnmark S, Garg N, Andersson CM, Rudling M, Sjoberg F, Angelin B, Baxter JD. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):663-7. Accompanying editorial: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):409-10.
Shah V, Nguyen P, Nguyen NH, Togashi M, Scanlan TS, Baxter JD, Webb P. Complex actions of thyroid hormone receptor antagonist NH-3 on gene promoters in different cell lines. Mol Cell Endocrinol. 2008 Dec 16;296(1-2):69-77.
Bryzgalova G, Effendic S, Khan A, Rehnmark S, Barbounis P, Boulet J, Dong G, Singh R, Shapses S, Malm J, Webb P, Baxter JD, Grover GJ.Anti-obesity, anti-diabetic, and lipid lowering effects of the thyroid receptor beta subtype selective agonist KB-141. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):262-7.
Estebanez-Perpina E, Arnold AA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ. A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci USA. 2007 104(41):16074-16079.
Estebanez-Perpina E, Arnold LA, Jouravel N, Togashi M, Blethrow J, Mar E, Nguyen P, Phillips KJ, Baxter JD, Webb P, Guy RK, Fletterick RJ. Structural insight into the mode of action of a direct inhibitor of coregulator binding to the thyroid hormone receptor. Mol Endocrinol. 2007 21(12):2919-2928.
Velasco LF, Togashi M, Walfish PG, Pessanha RP, Moura FN, Barra GB, Nguyen P, Rebong R, Yuan C, Simeoni LA, Ribeiro RC, Baxter JD, Webb P, Neves FA. Thyroid hormone response element organization dictates the composition of active receptor. J Biol Chem. 2007 282(17):12458-12466.