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Stuart Schreiber
Stuart Schreiber (born February 6, 1956) is an American chemist who is the Morris Loeb Research Professor at Harvard University, a co-founder of the Broad Institute, Howard Hughes Medical Institute Investigator, Emeritus, and a member of the National Academy of Sciences and National Academy of Medicine. He currently leads Arena BioWorks. His work integrates chemical biology and human biology to advance the science of therapeutics. Key advances include the discovery that small molecules can function as “molecular glues” that promote protein–protein interactions, the co-discovery of mTOR and its role in nutrient-response signaling, the discovery of histone deacetylases and (with Michael Grunstein and David Allis) the demonstration that chromatin marks regulate gene expression, the development and application of diversity-oriented synthesis to microbial therapeutics, and the discovery of vulnerabilities of cancer cells linked to genetic, lineage and cell-state features, inclu ...
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Chemical Biology
Chemical biology is a scientific discipline between the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and manipulation of biological systems. Although often confused with biochemistry, which studies the chemistry of biomolecules and regulation of biochemical pathways within and between cells, chemical biology remains distinct by focusing on the application of chemical tools to address biological questions. History Although considered a relatively new scientific field, the term "chemical biology" has been in use since the early 20th century, and has roots in scientific discovery from the early 19th century. The term 'chemical biology' can be traced back to an early appearance in a book published by Alonzo E. Taylor in 1907 titled "On Fermentation", and was subsequently used in John B. Leathes' 1930 article titled "The Harveian Oration on The ...
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FKBP
The FKBPs, or FK506 binding proteins, constitute a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence. FKBPs have been identified in many eukaryotes, ranging from yeast to humans, and function as protein folding chaperones for proteins containing proline residues. Along with cyclophilin, FKBPs belong to the immunophilin family. FKBP1A (also known as FKBP12) is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients with autoimmune disorders. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin, which binds cyclophilin. Both the FKBP-tacrolimus complex and the cyclosporin-cyclophilin complex inhibit a phosphatase called calcineurin, thus blocking signal transduction in the T-lymphocyte transduction pathway. This ther ...
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Lactacystin
Lactacystin is an organic compound naturally synthesized by bacteria of the genus ''Streptomyces'' first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. (1991). Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al. ''J. Antibiot.'' 44(1):113-6. The target of lactacystin was subsequently found to be the proteasome on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995. The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. Lactacystin was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. The transformation product of lactacystin clasto-lactacystin β-lactone (also known as omuralide) covalently modi ...
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Mammalian Target Of Rapamycin
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTORC1, mTOR complex 1 and mTORC2, mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and Transcription (genetics), transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also ...
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Sirolimus
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumour (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mammalian target of rapamycin (mTOR) kinase inhibitor that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity. This compound also has a use in cardiovascular drug-eluting stent technologies to inhibit restenosis. It is produced by the bacterium '' Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially deve ...
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David M
David (; , "beloved one") was a king of ancient Israel and Judah and the third king of the United Monarchy, according to the Hebrew Bible and Old Testament. The Tel Dan stele, an Aramaic-inscribed stone erected by a king of Aram-Damascus in the late 9th/early 8th centuries BCE to commemorate a victory over two enemy kings, contains the phrase (), which is translated as " House of David" by most scholars. The Mesha Stele, erected by King Mesha of Moab in the 9th century BCE, may also refer to the "House of David", although this is disputed. According to Jewish works such as the '' Seder Olam Rabbah'', '' Seder Olam Zutta'', and '' Sefer ha-Qabbalah'' (all written over a thousand years later), David ascended the throne as the king of Judah in 885 BCE. Apart from this, all that is known of David comes from biblical literature, the historicity of which has been extensively challenged,Writing and Rewriting the Story of Solomon in Ancient Israel; by Isaac Kalimi; page 3 ...
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ARIAD Pharmaceuticals
ARIAD Pharmaceuticals, Inc. was an American oncology company, now part of Takeda Oncology, which was founded in 1991 by Harvey J. Berger, M.D. and headquartered in Cambridge, Massachusetts. ARIAD engaged in the discovery, development, and commercialization of medicines for cancer patients. ARIAD’s most prominent drug discoveries include Iclusig, designed for patients with all forms of Philadelphia chromosome-positive h+ chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who are resistant to or unable to tolerate other tyrosine kinase inhibitors, and brigatinib, a lung cancer drug which has completed its registration trial in ALK fusion driven non-small cell lung cancer as of June 2016 and was approved in the U.S. in April 2017. In January 2017, Takeda announced it would acquire ARIAD for $5.2 billion, expanding the company's oncology and hematology business. On February 16, 2017, Takeda Pharmaceuticals, Ltd. announced it had completed its acquisition o ...
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Erythropoiesis
Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin.Sherwood, L, Klansman, H, Yancey, P: ''Animal Physiology'', Brooks/Cole, Cengage Learning, 2005. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells (erythrocytes). In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the liver. After seven months, erythropoiesis occurs in the bone marrow. Increased ...
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TGFβ
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in whic ...
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NFAT
Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems. NFAT was first discovered as an activator for the transcription of Interleukin 2, IL-2 in T cells (as a regulator of T cell immune response) but has since been found to play an important role in regulating many more body systems. NFAT transcription factors are involved in many normal body processes as well as in development of several diseases, such as inflammatory bowel diseases and several types of cancer. NFAT is also being investigated as a drug target for several different disorders. Family members The NFAT transcription factor family consists of five members: NFATC1, NFATc1, NFATC2, NFATc2, NFATC3, NFATc3, NFATC4, NFATc4, and NFAT5. NFATc1 through NFATc4 are regulated by calciu ...
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Stanford University
Leland Stanford Junior University, commonly referred to as Stanford University, is a Private university, private research university in Stanford, California, United States. It was founded in 1885 by railroad magnate Leland Stanford (the eighth List of governors of California, governor of and then-incumbent List of United States senators from California, United States senator representing California) and his wife, Jane Stanford, Jane, in memory of their only child, Leland Stanford Jr., Leland Jr. The university admitted its first students in 1891, opening as a Mixed-sex education, coeducational and non-denominational institution. It struggled financially after Leland died in 1893 and again after much of the campus was damaged by the 1906 San Francisco earthquake. Following World War II, university Provost (education), provost Frederick Terman inspired an entrepreneurship, entrepreneurial culture to build a self-sufficient local industry (later Silicon Valley). In 1951, Stanfor ...
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Gerald Crabtree
Gerald R. Crabtree is the David Korn Professor at Stanford University and an Investigator in the Howard Hughes Medical Institute. He is known for defining the Ca2+-calcineurin-NFAT signaling pathway, pioneering the development of synthetic ligands for regulation of biologic processes and discovering chromatin regulatory mechanisms involved in cancer and brain development. He is a founder of Ariad Pharmaceuticals, Amplyx Pharmaceuticals, Foghorn Therapeutics, and Shenandoah Therapeutics (Shenandoah Therapeutics was mentioned in a July 26, 2023 New York Times online article by Gina Kolata). Education and training Crabtree grew up near Wellsburg, West Virginia, earned his B.S. in Chemistry and Mathematics from West Liberty State College and his M.D. from Temple University. While at medical school, he became interested in laboratory research and started to work at Dartmouth College with Allan Munck on the biochemistry of steroid hormones. Key discoveries 1980s, 1990s and 2010s I ...
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