Robert
Middle Name
Brian
York, Ph.D.
Middle Name
Brian
Picture
Positions
- Associate Professor
-
Molecular and Cellular Biology
Baylor College of Medicine
Houston, TX US
- Faculty Senator
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Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas United States
At-Large Representative
- Member
-
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Addresses
- Laboratory (Lab)
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BCM-Michael DeBakey Center
Room: BCMM-M810
Houston, TX 77030
United States
Phone: (713) 798-4178
york@bcm.edu
Professional Interests
- Liver Cancer
- Hepatic Metabolism
- Inflammation
- Calcium Signaling
Professional Statement
Our research is focused on understanding the physiological contributions of transcriptional coregulators and their upstream signaling inputs. The majority of our research is geared toward unraveling the metabolic and inflammatory pathways involved in liver homeostasis and disease. Over the past decade, we have defined the Steroid Receptor Coactivator (SRC) family as master gatekeepers of systems metabolism. We utilize a variety of in vitro and in vivo models to elucidate novel functions of these potent transcriptional regulators.In search of the upstream signaling inputs to the SRCs, we have recently identified the calcium kinase signaling cascade as a potent regulator of SRC function. These studies have evolved into a new research arm of the laboratory that is dedicated to understanding how perturbations in calcium signaling results in aberrancies in hepatic metabolism, inflammation and angiogenesis as a predisposition for liver disease. Importantly, this triad of processes are central to the development of metabolically induced pathologies that begin with benign hepatic steatosis, but quickly progress to Non Alcoholic Fatty Liver Disease (NAFLD), Non Alcoholic Steatohepatitis (NASH) and ultimately to Hepatocellular Carcinoma (HCC). Our long-term goals are focused on developing selective inhibitors against these signaling molecules as potential therapies for metabolically related liver disease.
Websites
Selected Publications
- Zhu B., Zhang Q., Pan Y., Mace E.M., York B., Antoulas A.C., Dacso C.C. and O’Malley B.W. "A Cell-Autonomous Mammalian 12 hr Clock Coordinates Metabolic and Stress Rhythms." Cell Metab.2017/June6;25(6):1305-1319. Pubmed PMID: 28591634
- Foulds C.E., Trevino L.S., York B. and Walker C.L. "Endocrine-disrupting chemicals and fatty liver disease." Nat Rev Endocrinol.2017/May19;: Pubmed PMID: 28524171
- Suresh S, Durakoglugil D, Zhou X, Zhu B, Comerford SA, Xing C, Xie XJ, York B, O'Donnell KA. "SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer." PLoS Genet.2017/March8;13(3):e1006650. Pubmed PMID: 28273073
- Koh EH, Chen Y, Bader DA, Hamilton MP, He B, York B, Kajimura S, McGuire SE, Hartig SM. "Mitochondrial Activity in Human White Adipocytes Is Regulated by the Ubiquitin Carrier Protein 9/microRNA-30a Axis." J Biol Chem.2016/October10;291(47):24747-24755. Pubmed PMID: 27758866
- Fleet T, Stashi E, Zhu B, Rajapakshe K, Marcelo KL, Kettner NM, Gorman BK, Coarfa C, Fu L, O'Malley BW, York B. "Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology." J Biol Rhythms. 2016 October ; 31 (5): 443-60. Pubmed PMID: 27432117
- Marcelo K.L., Means A.R. and York B. "The Ca2+/Calmodulin/CaMKK2 Axis: Nature's Metabolic CaMshaft." Trends Endocrinol Metab. 2016 October ; 27 (10): 706-18. Pubmed PMID: 27449752
- Marcelo KL, Ribar T, Means CR, Tsimelzon A, Stevens RD, Ilkayeva O, Bain JR, Hilsenbeck SG, Newgard CB, Means AR, York B. "Research Resource: Roles for Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) in Systems Metabolism." Mol Endocrinol. 2016 May ; 30 (5): 557-72. Pubmed PMID: 27003444
- Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR. "Asprosin, a Fasting-Induced Glucogenic Protein Hormone." Cell. 2016 April 14; : Pubmed PMID: 27087445
- Nikolai BC, Lanz RB, York B, Dasgupta S, Mitsiades N, Creighton CJ, Tsimelzon A, Hilsenbeck SG, Lonard DM, Smith CL, O'Malley BW. "HER2 Signaling Drives DNA Anabolism and Proliferation through SRC-3 Phosphorylation and E2F1-Regulated Genes." Cancer Res. 2016 March 15; 76 (6): 1463-75. Pubmed PMID: 26833126
- Zhu B., Gates L., Stashi E., Dasgupta S., Gonzales N., Dean A., Dacso C.C., York B.* and O’Malley B.W. "Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude via REV-ERB Loading.." Mol. Cell. 2015 60 (5): 769-83. Pubmed PMID: 26611104
- Fleet T., Zhang B., Lin F., Zhu B., Dasgupta S., Stashi E., Tacket B., Thevananther S., Rajapakshe K., Gonzales N., Dean A., Mao J., Malovannaya A., Qin J., Coarfa C., DeMayo F., Dacso C.C., Foulds C., O’Malley B.W. and York B. "SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis." PNAS. 2015 October 20; 112 (44): E6068-6077. Pubmed PMID: 26487680
- Hartig S.M., Bader D.A., Abadie K.V., Motamed M., Hamilton M.P., Wang W., Long W., York B., Chan L., Bajaj M., Moore D.D., Mancini M.A., and McGuire S.E. "Ubc9 impairs activation of the brown fat energy metabolism program in human adipocytes.." Molecular Endocrinology. 2015 29 (9): 1320-1333. Pubmed PMID: 26192107
- Lin F., Marcelo K.L., Rajapakshe K., Coarfa C., Dean A., Wilganowski N., Robinson H., Sevick, E., Bissig, K.D. Goldie L.C., Means A.R. and York B. "The CaMKK2/CaMKIV Relay is an Essential Regulator of Hepatic Cancer." Hepatology. 2015 62 (2): 505-520. Pubmed PMID: 25847065
- Marcelo K.L., Lin F., Rajapakshe K., Dean A., Gonzales N., Coarfa C., Means A.R., Goldie L.C., and York B. "Deciphering hepatocellular responses to metabolic and oncogenic stress.." Journal of Biological Methods. 2015 2 (3): e28. Pubmed PMID: 26504887
- Tannour-Louet M., York B.*, Tang K., Stashi E., Suoling Z., Stevens R.D., Xu J., Newgard C.B., O’Malley B.W. and Louet J.-F. "Hepatic SRC-1 Activity Orchestrates Transcriptional Circuitries of Amino Acid Pathways." Molecular Endocrinology. 2014 28 (10): 1707-1718. Pubmed PMID: 25148457
- Stashi E., York B. and O’Malley B.W. "Steroid Receptor Coactivators: Servants and Masters for Control of Systems Metabolism.." Trends in Endocrinology and Metabolism. 2014 25 : 337-347. Pubmed PMID: 24953190
- Stashi E., Lanz R.B., Mao J., Reineke E.L., Kettner N., Reineke L.C., Dasgupta S., Dean A., Stevenson C., Sivasubramanian N., DeMayo F., York B., Fu L., O’Malley B.W. "SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm.." Cell Reports. 2014 6 (4): 633-645. Pubmed PMID: 24529706
- Stashi E., Wang L., Mani S., York B. and O’Malley B.W. "Research Resource: Loss of the Steroid Receptor Coactivators confers neurobehavioral consequences.." Molecular Endocrinology. 2013 27 (10): 1776-87. Pubmed PMID: 23927929
- York B., Sagen J.V., Tsimelzon A., Louet J.F., Chopra A.R., Stevens R.D., Wenner B.R., Ilkayeva O., Bain J.R., Reineke E.L., Xu J., Hilsenbeck S.G., Newgard C.B. and O’Malley B.W. "Research Resource: Tissue- and Pathway-Specific Metabolomic Profiles of the Steroid Receptor Coactivator (SRC) Family.." Molecular Endocrinology. 2012 27 (2): 366-80.
- O’Donnell K.A., Keng V.W., York B., Reineke E.L., Seo D., Fan F., Silverstein K.A., Schrum C.M., Xie W.R., Mularoni L., Wheelan S.J., Torbenson M., O’Malley B.W., Largaespada D.A., and Boeke J.D. "A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for NCOA2/SRC-2 in liver cancer.." PNAS. 2012 109 : 1377-86. Pubmed PMID: 22556267
- York B., Reineke E.L., Sagen J.V., Nikolai B., Zhou S., Louet J.-F., Chopra A.R., Chen X., Reed G., Noebels J., Adesina A.M., Yu H., Wong L.J., Tsimelzon A., Hilsenbeck S., Stevens R.D., Wenner B.R., Ilkayeva O., Xu J., Newgard C.B. and O’Malley B.W. "Ablation of Steroid Receptor Coactivator-3 resembles the human CACT metabolic myopathy.." Cell Metabolism. 2012 15 (5): 752-63. Pubmed PMID: 22560224
- Reineke E.L., York B., Stashi E., Chen X., Tsimelzon A., Xu J., Newgard C.B., Taffet G.E., Taegtmeyer H., Entman M.L., and O’Malley B.W. "SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart.." PLoS One. 2012 7 (12): e53395. Pubmed PMID: 23300926
- York B. and O’Malley B.W. "Steroid receptor coactivator (SRC) family: Masters of systems biology.." JBC. 2010 285 : 38743-38750. Pubmed PMID: 20956538
- Louet J.F., Chopra A.R., Sagen J.V., An J., York B., Tannour-Louet M., Saha P.K., Stevens R.D., Wenner B.R., Ilkayeva O.R., Bain J.R., Zhou S., DeMayo F., Xu J., Newgard C.B., and O'Malley B.W. "The coactivator SRC-1 is an essential coordinator of hepatic glucose production.." Cell Metabolism. 2010 12 : 606-618. Pubmed PMID: 21109193
- Pond, A.C., Herschkowitz J.I., Schwertfeger K.L., Welm B., Zhang Y., York B., Cardiff R.D., Hilsenbeck S., Perou C.M., Creighton C.J., Lloyd R.E. and Rosen J.M. "Fibroblast growth factor receptor signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-Wnt-1 mouse model of breast cancer.." Cancer Research. 2010 70 : 4868-4879. Pubmed PMID: 20501844
- York B., Yu C., Sagen J.V., Liu Z., Nikolai B.C., Wu R.C., Finegold M., Xu J., and O'Malley B.W. "Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology.." PNAS. 2010 107 : 11122-27. Pubmed PMID: 20534466
- Chopra A.R., Louet J.F., Saha P., An J., DeMayo F., Xu J., York B., Karpen S., Finegold M., Moore D., Chan L., Newgard C.B., and O’Malley B.W. "Absence of the SRC-2 coactivator results in glycogenopathy resembling Von Gierke’s disease.." Science. 2008 332 : 1395-1399. Pubmed PMID: 19039140
- Yu C., York B., Wang S., Feng Q., Xu J. and O’Malley B.W. "An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response.." Mol. Cell. 2007 25 : 765-778. Pubmed PMID: 17349961
- York B., Lou, D., and Noonan, D. J "Tuberin nuclear localization can be regulated by phosphorylation of its carboxyl terminus." Molecular Cancer Research. 2006 : Pubmed PMID: 17114346
- York B., Lou, D., Panettieri Jr., R. A., Krymskaya, V. P., Vanaman, T. C. and Noonan, D. J. "Cross-talk between tuberin, calmodulin, and estrogen signaling pathways." FASEB J. 2005 19 : 1-23. Pubmed PMID: 15851513
- Finlay, G. A., York B., Karas, R. H., Fanburg, B. L., Zhang, H., Kwiatkowski, D. J., and Noonan, D. J. "Estrogen-induced smooth muscle cell growth is regulated by tuberin and associated with altered activation of platelet-derived growth factor receptor-beta and ERK-1/2." J Biol Chem. 2004 279 : 23114-23122. Pubmed PMID: 15039427
Funding
- CaMKK2 inhibitors for therapeutic treatment of hepatic cancer - #M2014 (04/01/2014 - 03/31/2017) Grant funding from Adrienne Helis Malvin Medical Research Foundation
- Microgravity as an accelerator for OMIC analysis of human disease (07/01/2014 - 06/30/2019) Grant funding from Center for the Advancement of Science in Space (CASIS)
- Hormonal regulation of a Ca2+/AMPK signaling pathway - #2 R01 GM033976-27A1/30 (07/01/2012 - 06/30/2016) Grant funding from NIH-RO1
- Genetic and Metabolic Fingerprints of Coactivators “Program Project” - #P01 DK059820 (07/01/2012 - 06/30/2017) Grant funding from NIH-NIDDK
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