Division of Nephrology-Hypertension

Michael E. Baker, Ph.D.

Researcher
Curriculum Vitae

Phone : (858) 534-8317
E-mail : mbaker@ucsd.edu
Location : Pharmaceutical Sci Bldg
Room : 2111
Mail Code : 0693
Mailing Address :9500 Gilman Drive # 0693
La Jolla, CA 92093-0693

Research Interests

  1. Evolution of steroid hormone signaling in lamprey, sharks, zebrafish, xenopus, chickens and humans.
  2. Mechanism of steroid binding to receptors and steroid dehydrogenases.
  3. Hormonal activities of environmental compounds [endocrine disruptors].
  4. Effects of plant-derived compounds on hormone action and the evolutionary basis for this activity.

The general theme of our research is understand the evolution of steroid hormone action through analysis of how steroids bind to their receptors and steroid dehydrogenases, and the effects of plant-derived compounds and environmental pollutants on steroid hormone action. We use Dobzhansky's insight "Nothing in biology makes sense except in the light of evolution" to investigate these aspects of steroid hormone action.

Evolution of steroid receptors. Steroid receptors for estrogens, androgens, progestins, glucocorticoids, and mineralocorticoids arose about 600 million years ago, prior to the Cambrian explosion. To understand the evolution of structure and function in steroid receptors in lamprey, sharks and amphioxus, we are collaborating with colleagues in Japan (Dr. Yohinao Katsu, Dr. Taisen Iguchi) and Switzerland (Dr. Alex Odermatt) to study transcriptional activation by estrogens, glucocorticoids and mineralocorticoids of their steroid receptors in sharks, zebrafish, Xenopus, chickens and humans. In addition, we have modeled the 3D structures of steroid receptors in lamprey, sharks and amphioxus to investigate details of the interaction of the receptors with steroids.

Chemical disruption of steroid hormone action. Some pesticides that are designed to interfere with insect physiology have structures that resemble steroids and other lipophilic hormones that bind to human proteins with profound effects on human physiology. Indeed, many pesticides, plastics and other synthetic chemicals have entered our food supply and bind to steroid receptors and act as endocrine disruptors. The effects of these compounds on fetal health are of great concern.

Some phytochemicals are hormones. Compounds in plants can mimic steroids. In fact, herbals have long been used to treat problems associated with endocrine physiology. For example, licorice root has glucocorticoid and mineralocorticoid activities in humans. Licorice inhibits a steroid dehydrogenase that converts cortisol to cortisone, an inactive steroid. By inhibiting this steroid dehydrogenase, licorice increases cortisol levels, which leads to a glucocorticoid response, as well as a mineralocorticoid response in the kidney.

Hormone-like activities of flavonoids in soy, flax, citrus, etc. have made these compounds of interest for controlling various hormone-dependent cancers, including breast and prostate cancer. We are studying the binding of phytochemicals to steroid receptors. There is an evolutionary basis for the endocrine activities of some phytochemicals in humans. Some compounds interfere with animal physiology as a defense against consumption by animals. Unfortunately, those phytochemicals that have cyclic structures similar to that of steroids disrupt human physiology.

Selected Publications
163. Baker ME, Lathe R The promiscuous estrogen receptor: evolution of physiological estrogens and response to phytochemicals and endocrine disruptors. J. Steroid Biochemistry & Molecular Biology 2018. https://www.sciencedirect.com/science/article/pii/S0960076018303571?dgcid=author
162. Katsu Y, Oka K, Baker ME Evolution of steroid specificity in human, chicken, alligator, frog and zebrafish mineralocorticoid receptors: Allosteric interactions affect steroid specificity. Science Signaling, 2018 Jul 3;11(537). pii: eaao1520. doi: 10.1126/scisignal.aao1520. https://www.biorxiv.org/content/early/2017/08/04/151233
161. Katsu Y, Baker ME. Progesterone activation of zebrafish mineralocorticoid receptor may influence growth of some transplanted tumors. Proceedings of the National Academy of Sciences 115, E2908-E2909, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879718/
160. Baker ME, Katsu Y. 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function. J Endocrinol. 234, T1-T16, 2017. https://www.biorxiv.org/content/early/2017/01/06/098921
159. Sugimoto A, Oka K, Sato R, Adachi S, Baker ME, Katsu Y. Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar. Biochem J. 473, 3655-3665, 2016. https://www.ncbi.nlm.nih.gov/pubmed/27520308
157. Katsu Y, Kohno S, Oka K, Baker ME. Evolution of corticosteroid specificity for human, chicken, alligator and frog glucocorticoid receptors. Steroids. 113, 38-45, 2016. https://www.biorxiv.org/content/early/2016/04/21/036665
156. Mani O, Nashev LG, Livelo C, Baker ME, Odermatt A. Role of Pro-637 and Gln-642 in human glucocorticoid receptors and Ser-843 and Leu-848 in mineralocorticoid receptors in their differential responses to cortisol and aldosterone. J. Steroid Biochem. Mol. Biol. 159, 31-40, 2016. https://www.ncbi.nlm.nih.gov/pubmed/26907965
154. Oka K, Hoang A, Okada D, Iguchi T, Baker ME, Katsu Y. Allosteric role of the amino-terminal A/B domain on corticosteroid transactivation of gar and human glucocorticoid receptors. J. Steroid Biochem. Mol. Biol. 154, 112-119, 2015. https://www.ncbi.nlm.nih.gov/pubmed/26247481
152. Rossier B, Baker ME, Studer RA. Epithelial Sodium Transport and Its Control by Aldosterone: The Story of Our Internal Environment Revisited. Physiological Reviews 95, 297-340, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25540145
151. Baker ME, Nelson DR, Studer RA. Origin of the response to adrenal and sex steroids: Roles of promiscuity and co-evolution of enzymes and steroid receptors. The Journal Steroid Biochem. Mol. Biol. 151, 12-24, 2015. https://www.sciencedirect.com/science/article/pii/S0960076014002556
150. Baker ME. Expanding the structural footprint of xenoestrogens. Endocrine Disruptors, 2, e967138, 2014. ttps://www.tandfonline.com/doi/full/10.4161/23273739.2014.967138
149. Baker ME. The Microbiome as a Target for Endocrine Disruptors: Novel Chemicals May Disrupt Androgen and Microbiome-mediated Autoimmunity. Endocrine Disruptors, 2, e964539, 2014. https://www.tandfonline.com/doi/full/10.4161/23273739.2014.964539
143. Baker ME, Funder JW, Kattoula SR. Evolution of hormone selectivity in glucocorticoid and mineralocorticoid receptors. J. Steroid Biochem. Mol. Biol. 137, 57-70, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23907018
141. Baker ME, What are the physiological estrogens? Steroids 78, 337-340, 2013.
140. Baker ME, Chandsawangbhuwana C. 3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor  and estrogen receptor β. PLoS One 7, e46078, 2012. https://www.ncbi.nlm.nih.gov/pubmed/23056236
139. Baker ME, Uh KY, Chandsawangbhuwana C. 3D models of human ER and ERβ complexed with 5-androsten-3β,17β-diol. Steroids 77, 1192-1197. 2012.
137. Baker ME, Uh KY, Asnaashari P. 3D models of lamprey corticoid receptor complexed with 11-deoxycortisol and deoxycorticosterone. Steroids 76, 1451-1457, 2011.
134. Baker ME. Insights from the structure of estrogen receptor into the evolution of estrogens: Implications for endocrine disruption. Biochem. Pharmacol. 82, 1-8, 2011.
133. Baker ME, Asnaashari P, Chang DJ, McDonnell S. 3D models of lamprey progesterone receptor complexed with progesterone, 7-hydroxy-progesterone and 17-hydroxy-progesterone. Steroids 76, 169-176, 2011.
132. Baker ME. Origin and diversification of steroids: co-evolution of enzymes and nuclear receptors. Mol. Cell. Endocrinol. 334, 14-20, 2011.
131. Baker ME. 11beta-hydroxysteroid dehydrogenase-type 2 evolved from an ancestral 17beta-hydroxysteroid dehydrogenase-type 2. Biochem. Biophys. Res. Commun. 399, 215-220, 2010.
130. Baker ME Evolution of 11beta-hydroxysteroid dehydrogenase-type 1 and 11beta-hydroxysteroid dehydrogenase-type 3. FEBS Lett. 584, 2279-2284, 2010.
129. Markov GV, Tavares R, Dauphin-Villemant C, Demeneix BA, Baker ME, Laudet V. Independent elaboration of steroid hormone signaling pathways in metazoans. Proc Natl Acad Sci USA. 106, 11913-11918, 2009.
128. Baker ME, Chang DJ, Chandsawangbhuwana C. 3D model of lamprey estrogen receptor with estradiol and 15alpha-hydroxy-estradiol. PLoS ONE 4, e6038, 2009. https://www.ncbi.nlm.nih.gov/pubmed/19557178
126. Baker et al. Analysis of endocrine disruption in Southern California coastal fish using an aquatic multispecies microarray. Environ. Health Perspect. 117, 223-230, 2009.
123. Baker M E. Trichoplax, the simplest known animal, contains an estrogen-related receptor but no estrogen receptor: Implications for estrogen receptor evolution. Biochem. Biophys. Res. Commun. 375, 623-627, 2008.
115. Baker ME, Chandsawangbhuwana C, Ollikainen N, Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors. BMC Evol. Biol. 7, 24, 2007. https://www.ncbi.nlm.nih.gov/pubmed/17306029
100. Baker M E. Evolution of adrenal and sex steroid action in vertebrates: A ligand-based mechanism for complexity. BioEssays 25, 396-400, 2003.
82. Baker M E. Steroid receptor phylogeny and vertebrate origins. Molec. Cell. Endocrinol. 135, 101-107, 1997.