Nancy Carrasco

Last updated
Nancy Carrasco
Born
Mexico City, Mexico
Alma mater School of Chemistry, UNAM
School of Medicine, UNAM
Spouse Samuel Zyman
Children1
AwardsPew Award, (1989)

Beckman Young Investigators Award (1991)

Maria Sibylla Merian Award, Germany (1998)

Merck Prize (European Thyroid Association), Poland (2001)

Contents

Rose Pitt-Rivers Lecturer at the British Endocrine Society Meeting, Glasgow (2003)

Coleman Fellow in Life Sciences, Ben-Gurion University, Israel (2008)

Marshall S. Horwitz Faculty Prize for Research Excellence (2009)

Light of Life Award (2010)

Member of the National Academy of Sciences (2015)

Sidney H. Ingbar Distinguished Lecturer, American Thyroid Association (2016)

Plenary Lecturer, 1st International Meeting on Science, Health, and Gender, Mexico (2018)

Member of the National Academy of Medicine (2020)
Scientific career
Fields Molecular physiology
Biochemistry

Biophysics

Cell physiology
Institutions Vanderbilt University
Yale University
Albert Einstein College of Medicine

Nancy Carrasco is a professor in, and the chair of, the Department of Molecular Physiology and Biophysics at Vanderbilt University. [1] Carrasco has conducted research in the fields of biochemistry, biophysics, molecular physiology, molecular endocrinology, and cancer. [2] She cloned the sodium/iodide symporter (NIS), a breakthrough in thyroid pathophysiology with ramifications for many other fields, including structure/function of transport proteins, molecular endocrinology, gene transfer studies, cancer, and public health (she has served on the Environmental Protection Agency's science advisory board). [3] [1]

Early life and education

Carrasco was born in Mexico City, Mexico. She obtained her M.D. from the School of Medicine and her M.S. in Biochemistry from the School of Chemistry at the National Autonomous University of Mexico in 1980 and 1981, respectively. [4] She subsequently became a postdoctoral fellow at the Roche Institute of Molecular Biology [2] in New Jersey, for which she received a Fogarty International Fellowship from the National Institutes of Health. She did her postdoctoral training in the laboratory of Ronald Kaback. [5] In the course of her postdoctoral work, Carrasco—among other things—generated monoclonal and site-directed polyclonal antibodies against the lactose permease of E. coli . She used these antibodies to determine the topology of the lactose permease in the membrane of E. coli, and identified the proton translocation pathway that provides the driving force for lactose accumulation by E. coli. [5]

Career

In 1987, Carrasco joined the faculty of the Albert Einstein College of Medicine, and in 2011 she moved to the Yale School of Medicine. [1] At Yale, in 2018, Carrasco became the C.N.H. Long Professor of Physiology. [6]

In the summer of 2019, Carrasco moved again, this time to Vanderbilt University, where she became the Chair of the Department of Molecular Physiology and Biophysics. [1]

She is a member of the Editorial Board for PNAS . [7]

Sodium/iodide symporter

Carrasco's research group was the first to clone, and extensively characterize at the molecular level, the sodium/iodide symporter (NIS), the key plasma membrane protein that mediates the active transport of iodide into the thyroid, the lactating breast, and other tissues. [6] [1] Carrasco's group has obtained a great deal of mechanistic information on NIS by determining the molecular requirements of this protein at amino acid positions at which mutations have been found in patients. Her group also discovered that, although NIS transports iodide but not chloride (unlike chloride transporters and channels, which transport both), NIS also transports other anions, including the environmental pollutant perchlorate. In addition, her group recently identified an allosteric site in NIS—which, when occupied by an oxyanion such as perchlorate, completely changes the mechanism by which NIS transports iodide. This finding indicates that perchlorate pollution may well be more dangerous to human health than previously thought.

The Carrasco group's NIS knockout mouse has made it possible to generate an animal model of hypothyroidism without the need to use any drugs (e.g., methimazole or propylthiouracil). This animal model has proven to be an extremely valuable tool for investigating the cross-talk between different tissues regulated by the thyroid hormones.

Personal life

Nancy Carrasco is married to Samuel Zyman, a composer with a degree in medicine from the National Autonomous University of Mexico and a doctorate in music composition from the Juilliard School who is now a faculty member at the Juilliard School and at the Blair School of Music at Vanderbilt University. [1] Carrasco and Zyman met on their first day of medical school. [1] They have a son, Erik Zyman, a theoretical syntactician who is a faculty member at the University of Chicago. [8] [1]

Awards

The Pew Award is given based on biomedical research. [16] The Beckman Young Investigators Award is given to young members in the early stages of their careers in chemical and life sciences, providing them with research support. [17] Carrasco was the first person to be awarded the Maria Sibylla Merian Award, given by the Essen College of Gender Studies in 1998. [18] The Light of Life Award is given by the Light of Life Foundation to research that has impacted the understanding of Thyroid cancers. [12] The Sidney H. Ingbar Distinguished Lecturer award is given to individuals who have provided major contributions to the research on thyroid. [19]

Additionally, she serves on the editorial board of The Journal of General Physiology , [20] and has served as the President of the Society of Latin American Biophysicists. [21]

Published works

Martín M, Modenutti CP, Peyret V, Geysels RC, Darrouzet E, Pourcher T, Masini-Repiso AM, Martí MA, Carrasco N, Nicola JP. (2019) A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter. Endocrinology. 160: 156–168. PMID 30496374 DOI: 10.1210/en.2018-00603 [22]

Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. (2017) Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings of the National Academy of Sciences of the United States of America. 114: E9172-E9180. PMID 29073114 DOI: 10.1073/pnas.1707797114 [22]

Ferrandino G, Kaspari RR, Reyna-Neyra A, Boutagy NE, Sinusas AJ, Carrasco N. (2017) An extremely high dietary iodide supply forestalls severe hypothyroidism in Na(+)/I(-) symporter (NIS) knockout mice. Scientific Reports. 7: 5329. PMID 28706256 DOI: 10.1038/s41598-017-04326-z [22]

Ravera S, Reyna-Neyra A, Ferrandino G, Amzel LM, Carrasco N. (2017) The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annual Review of Physiology. 79: 261–289. PMID 28192058 DOI: 10.1146/annurev-physiol-022516-034125 [22]

Ferrandino G, Nicola JP, Sánchez YE, Echeverria I, Liu Y, Amzel LM, Carrasco N. (2016) Na+ coordination at the Na2 site of the Na+/I- symporter. Proceedings of the National Academy of Sciences of the United States of America. PMID 27562170 DOI: 10.1073/pnas.1607231113 [22]

Renier C, Do J, Reyna-Neyra A, Foster D, De A, Vogel H, Jeffrey SS, Tse V, Carrasco N, Wapnir I. (2016) Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy. Oncotarget. PMID 27363025 DOI: 10.18632/oncotarget.10238 [22]

Ravera S, Quick M, Nicola JP, Carrasco N, Amzel LM. (2015) Beyond non-integer Hill coefficients: A novel approach to analyzing binding data, applied to Na+-driven transporters. The Journal of General Physiology. 145: 555–63. PMID 26009546 DOI: 10.1085/jgp.201511365 [22]

Nicola JP, Carrasco N, Masini-Repiso AM. (2015) Dietary I(-) absorption: expression and regulation of the Na(+)/I(-) symporter in the intestine. Vitamins and Hormones. 98: 1-31. PMID 25817864 DOI: 10.1016/bs.vh.2014.12.002 [22]

Oikawa T, Wauthier E, Dinh TA, Selitsky SR, Reyna-Neyra A, Carpino G, Levine R, Cardinale V, Klimstra D, Gaudio E, Alvaro D, Carrasco N, Sethupathy P, Reid LM. (2015) Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells. Nature Communications. 6: 8070. PMID 26437858 DOI: 10.1038/ncomms9070 [22]

Nicola JP, Reyna-Neyra A, Saenger P, Rodriguez-Buritica DF, Gamez Godoy JD, Muzumdar R, Amzel LM, Carrasco N. (2015) Sodium/Iodide Symporter Mutant V270E Causes Stunted Growth but No Cognitive Deficiency. The Journal of Clinical Endocrinology and Metabolism. 100: E1353-61. PMID 26204134 DOI: 10.1210/jc.2015-1824 [22]

Ravera S, Quick M, Nicola JP, Carrasco N, Amzel LM. (2015) Beyond non-integer Hill coefficients: A novel approach to analyzing binding data, applied to Na+-driven transporters. The Journal of General Physiology. 145: 555–63. PMID 26009546 DOI: 10.1085/jgp.201511365 [22]

Arriagada AA, Albornoz E, Opazo MC, Becerra A, Vidal G, Fardella C, Michea L, Carrasco N, Simon F, Elorza AA, Bueno SM, Kalergis AM, Riedel CA.(2015) Excess iodide induces an acute inhibition of the sodium/iodide symporter in thyroid male rat cells by increasing reactive oxygen species. Endocrinology. 156: 1540–51. PMID 25594695 DOI: 10.1210/en.2014-1371 [22]

Related Research Articles

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Thyroid follicular cell</span>

Thyroid follicular cells (also called thyroid epithelial cells or thyrocytes) are the major cell type in the thyroid gland, and are responsible for the production and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). They form the single layer of cuboidal epithelium that makes up the outer structure of the almost spherical thyroid follicle.

<span class="mw-page-title-main">Cotransporter</span> Type of membrane transport proteins

Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.

<span class="mw-page-title-main">Wolff–Chaikoff effect</span> Effect of iodine on the thyroid

The Wolff–Chaikoff effect is a presumed reduction in thyroid hormone levels caused by ingestion of a large amount of iodine.

<span class="mw-page-title-main">Thyroid peroxidase</span> Enzyme expressed mainly in the thyroid gland

Thyroid peroxidase, also called thyroperoxidase (TPO), thyroid specific peroxidase or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3), the thyroid hormones. In humans, thyroperoxidase is encoded by the TPO gene.

<span class="mw-page-title-main">Thyrotropin receptor</span> Mammalian protein found in Homo sapiens

The thyrotropin receptor is a receptor that responds to thyroid-stimulating hormone and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH receptor is a member of the G protein-coupled receptor superfamily of integral membrane proteins and is coupled to the Gs protein.

Pendrin is an anion exchange protein that in humans is encoded by the SLC26A4 gene . Pendrin was initially identified as a sodium-independent chloride-iodide exchanger with subsequent studies showing that it also accepts formate and bicarbonate as substrates. Pendrin is similar to the Band 3 transport protein found in red blood cells. Pendrin is the protein which is mutated in Pendred syndrome, which is an autosomal recessive disorder characterized by sensorineural hearing loss, goiter and a partial organification problem detectable by a positive perchlorate test.

<span class="mw-page-title-main">Gastric mucosa</span> Mucous membrane layer of the stomach

The gastric mucosa is the mucous membrane layer of the stomach, which contains the glands and the gastric pits. In humans, it is about 1 mm thick, and its surface is smooth, soft, and velvety. It consists of simple columnar epithelium, lamina propria, and the muscularis mucosae.

The sodium/phosphate cotransporter is a member of the phosphate:Na+ symporter (PNaS) family within the TOG Superfamily of transport proteins as specified in the Transporter Classification Database (TCDB).

An antithyroid agent is a hormone inhibitor acting upon thyroid hormones.

<span class="mw-page-title-main">Sodium/iodide cotransporter</span> Mammalian protein found in Homo sapiens

The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the SLC5A5 gene. It is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations (Na+) for each iodide anion (I−) into the cell. NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone.

<span class="mw-page-title-main">KCNE2</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily E member 2 (KCNE2), also known as MinK-related peptide 1 (MiRP1), is a protein that in humans is encoded by the KCNE2 gene on chromosome 21. MiRP1 is a voltage-gated potassium channel accessory subunit associated with Long QT syndrome. It is ubiquitously expressed in many tissues and cell types. Because of this and its ability to regulate multiple different ion channels, KCNE2 exerts considerable influence on a number of cell types and tissues. Human KCNE2 is a member of the five-strong family of human KCNE genes. KCNE proteins contain a single membrane-spanning region, extracellular N-terminal and intracellular C-terminal. KCNE proteins have been widely studied for their roles in the heart and in genetic predisposition to inherited cardiac arrhythmias. The KCNE2 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. More recently, roles for KCNE proteins in a variety of non-cardiac tissues have also been explored.

<span class="mw-page-title-main">PTTG1IP</span> Protein-coding gene in the species Homo sapiens

Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1), also known as PTTG1-binding factor (PBF), is a poorly characterised protein that in humans is encoded by the PTTG1IP gene located within the chromosomal region 21q22.3.

<span class="mw-page-title-main">Thyroid hormones</span> Hormones produced by the thyroid gland

Thyroid hormones are any hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, derived from food. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre.

<span class="mw-page-title-main">Iodotyrosine deiodinase</span> Protein-coding gene in the species Homo sapiens

Iodotyrosine deiodinase, also known as iodotyrosine dehalogenase 1, is a type of deiodinase enzyme that scavenges iodide by removing it from iodinated tyrosine residues in the thyroid gland. These iodinated tyrosines are produced during thyroid hormone biosynthesis. The iodide that is scavenged by iodotyrosine deiodinase is necessary to again synthesize the thyroid hormones. After synthesis, the thyroid hormones circulate through the body to regulate metabolic rate, protein expression, and body temperature. Iodotyrosine deiodinase is thus necessary to keep levels of both iodide and thyroid hormones in balance.

<span class="mw-page-title-main">Iodine in biology</span> Use of Iodine by organisms

Iodine is an essential trace element in biological systems. It has the distinction of being the heaviest element commonly needed by living organisms as well as the second-heaviest known to be used by any form of life. It is a component of biochemical pathways in organisms from all biological kingdoms, suggesting its fundamental significance throughout the evolutionary history of life.

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/iodide (Anti–Na+/I−) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies; they were renamed after the identification of their target antigen (TPO).

Measles virus encoding the human thyroidal sodium iodide symporter or MV-NIS is an attenuated oncolytic Edmonston (Ed) strain of measles virus.

Israel Lyon Chaikoff was a Canadian-American physiologist and biochemist, known for the Wolff–Chaikoff effect. He and his colleagues were pioneers in the use of radioactive iodine (iodine-131) to investigate thyroid function.

<span class="mw-page-title-main">Plummer effect</span>

The Plummer effect is one of several physiological feedforward mechanisms taking place in follicular cells of the healthy thyroid gland and preventing the development of thyrotoxicosis in situations of extremely high supply with iodine.

References

  1. 1 2 3 4 5 6 7 8 MacMillan, Leigh. "Carrasco to lead Department of Molecular Physiology and Biophysics". Vanderbilt University. Retrieved 2019-12-08.
  2. 1 2 "Nancy Carrasco, MD". Yale School of Medicine. Retrieved May 13, 2019.
  3. ↑ Dai, Ge; Levy, Orlie; Carrasco, Nancy (February 1996). "Cloning and characterization of the thyroid iodide transporter". Nature. 379 (6564): 458–460. Bibcode:1996Natur.379..458D. doi:10.1038/379458a0. ISSN   1476-4687. PMID   8559252. S2CID   4366019.
  4. 1 2 "Prof. Dr. Nancy Carrasco - Maria Sibylla Merian-Preisträgerin 1998" (in German). Retrieved May 13, 2019.
  5. 1 2 Carrasco, Nancy (2019-02-04). "Mentors: Ron KabackMentors: Ron Kaback". The Journal of General Physiology. 151 (2): 97–99. doi: 10.1085/jgp.201912322 . ISSN   0022-1295. PMC   6363408 . PMID   30674562.
  6. 1 2 "Dr. Nancy Carrasco named C.N.H. Long Professor". YaleNews. 2018-08-29. Retrieved 2019-12-08.
  7. ↑ "Editorial Board | Oncogene". Nature.
  8. ↑ MacMillan, Leigh (August 21, 2018). "Carrasco to lead Department of Molecular Physiology and Biophysics". Vanderbilt University. Retrieved May 13, 2019.
  9. ↑ "Nancy Carrasco, M.D." The Pew Charitable Trusts . Retrieved May 13, 2019.
  10. ↑ "Einstein Researcher Receives 2009 Beckman Foundation Young Investigator Award". May 13, 2009. Retrieved May 13, 2019.
  11. ↑ "Einstein Honors Dr. Nancy Carrasco With Its Third Annual Marshall S. Horwitz Faculty Prize for Research Excellence". February 27, 2009. Retrieved May 13, 2019.
  12. 1 2 "LoLF Honorary Awardees". Light of Life Foundation. Retrieved May 13, 2019.
  13. ↑ "Nancy Carrasco". National Academy of Sciences. Retrieved May 13, 2019.
  14. ↑ "American Thyroid Association Announces 2016 Sidney H. Ingbar Distinguished Lectureship Award Winner". September 21, 2016. Retrieved May 13, 2019.
  15. ↑ "National Academy of Medicine Elects 100 New Members". National Academy of Medicine. 2020-10-19. Retrieved 2020-10-21.
  16. ↑ "Program Details". pew.org. Retrieved 2019-12-08.
  17. ↑ "Beckman Young Investigator Program". Arnold and Mabel Beckman Foundation. Retrieved 2019-12-08.
  18. ↑ "Maria Sibylla Merian-Prize". www.uni-due.de. Retrieved 2019-12-08.
  19. ↑ "Sidney H. Ingbar Distinguished Lectureship Award". American Thyroid Association. Retrieved 2019-12-08.
  20. ↑ Gordon, Sharona E. (2018-02-05). "Looking in the rear-view mirror as we anticipate another 100 yearsReflecting on JGP's mission in 2018". The Journal of General Physiology. 150 (2): 169–174. doi: 10.1085/jgp.201811995 . ISSN   0022-1295. PMC   5806681 . PMID   29367199.
  21. ↑ "Dr. Nancy Carrasco named C.N.H. Long Professor". www.myscience.org. 29 August 2018. Retrieved 2019-12-08.
  22. 1 2 3 4 5 6 7 8 9 10 11 12 "Nancy Carrasco - Publications". academictree.org. Retrieved 2019-12-08.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.