SONG-YU YANG, M.D., Ph.D.
Research Scientist, NYS Office for People With Developmental Disabilities (OPWDD) Head, Laboratory of Medical Biochemistry, NYS Institute for Basic Research in Developmental Disabilities (NYSIBRDD) Professor, Graduate Center of the City University of New York (CUNY) Associated Editor, Journal of Alzheimer’s Disease, IOS Press Editor, Annals of Autism and Developmental Disorders, Remedy Publications
Tel. +1-7184945317 Fax +1-7186987916 Email: [email protected] [email protected]
Education:
1984 Ph.D. Biochemistry, The City University of New York, New York, USA 1960 M.D. (medical school diploma), Beijing Medical University, Beijing, China
Professional Experience:
2018 Associated Editor, Journal of Alzheimer’s Disease, IOS Press Editor, Annals of Autism and Developmental Disorders, Remedy Publications 2017 Editor, Med One, Qingres Ltd Editor, EC Endocrinology and Metabolism, Publons 2015 Editor, Journal of Chemical Biology & Therapeutics, OMICS Editor, SRL Alzheimer’s and Parkinson’s Disease, SciRes Literature 2007 Adjunct Professor, Graduate Center of the City University of New York 1994 Head, Laboratory of Medical Biochemistry, NYS Institute for Basic Research in Developmental Disabilities 1991 Investigator, American Heart Association 1988 Research Scientist, NYS Office for People With Developmental Disabilities 1985 Member, American Society for Biochemistry and Molecular Biology 1984 Research Associate, Research Foundation of the City University of New York 1981 Teaching Assistant, The City College of the City University of New York 1980 Assistant Professor, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Science 1965 Member, Chinese Medical Association 1964 Instructor, Peking Medical College, China
Research Interest:
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The goal of my research laboratory is to unravel the pathophysiological mechanism of orphan diseases such as 17β-HSD10 deficiency, Mental retardation, X-linked, Syndromic 10 as well as Alzheimer's disease for the development of effective treatments of neurodegenerative disorders. The research scope is an expansion of our previous research focus on the HSD17B10 gene and the gene product 17β-HSD10. My research group first cloned this gene from human brain, decoded the HSD17B10 gene structure, and characterized 17β-HSD10, which is a homotetra- meric mitochondrial multifunctional enzyme. We found 17β-HSD10 playing a critical part in the metabolism of isoleucine and neuroactive steroids. We discovered its unique role in the oxidative inactivation of allopregnanolone (ALLOP) and the biosynthesis of dihydrotestosterone (DHT). Based upon our findings we proposed a revised molecular switch theory. The maintenance of homeostasis of 17β-HSD10 is critical to the prevention and treatment of neurodegenerative disorders such as Alzheimer’s disease, Parkinson disease, and 17β-HSD10 deficiency, an interlectual developmental disability. Please see HSD17B10 in Wikipedia.org:
Representative Publications:
1. Yang SY, He XY, Dobkin C, Brown WT. (2021) Human HSD10 Deficiency results from Mutants of Type 10 17β-Hydroxysteroid Dehydrogenase rather than β-Amyloid-Binding Alcohol Dehydrogenase. Genes submitted for publication. 2. He XY, Dobkin C, Yang SY (2019)17beta-Hydroxysteroid dehydrogenases and neurosteroid metabolism in the central nervous system. Mol Cell Endocrinol 229, 111- 117. 3. He XY, Isaacs C, Yang SY. (2018) Roles of mitochondrial 17beta-hydroxysteroid dehydrogenase type 10 in Alzheimer’s disease. J Alz Dis 62, 665-673.
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4. Porcu P, Barron AM, Frye CA, Walf AA, Yang SY, He XY, Morrow AL, Panzica GC, Melcangi RC. (2016) Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research. J. Neuroendocrinol 28, 12351. 5. Yang SY, He XY., Dobkin C, Isaacs C, Brown WT. (2015) Mental retardation and isoleucine metabolism. In Branched Chain Amino Acids in Clinical Nutrition: Volume I, Nutrition and Health (Rajendram R., Preedy V.R., Patel V.B., eds), pp. 157-170, Springer, New York. 6. He XY, Dobkin C, Yang SY. (2015) A do-it-yourself protocol for making desired mutant proteins. J. Chem. Biol. Therap. 1, 101. Doi.org/10.4172/jcbt.1000001.
7. Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M. (2014) Roles of 17beta- hydroxysteroid dehydrogenase type 10 in neurodegenerative disorders. J. Steroid Biochem. Mol. Biol. 143, 460-472. 8. Yang SY., Dobkin C, He XY, Philipp M, Brown WT. (2013) A 5-methylcytosine hotspot responsible for the prevalent HSD17B10 mutation. Gene 515, 280-284. 9. Yang SY, Dobkin C, He XY, Brown WT. (2013) Transcription start sites and epigenetic analysis of the HSD17B10 proximal promoter. BMC Biochem. 14, 17.
10. He XY, Yang YX., Yang SY. (2013) Changes of the HSD17B10 gene expression levels in ulcerative colitis. Inflamm Bowel Dis 19, E23-24.
11. Yang SY, He XY., Miller D. (2011) Hydroxysteroid (17beta) dehydrogenase X in Human Health and Disease. Mol. Cell. Endocrinol. 343, 1-6.
12. He XY, Miller D, Yang SY. (2011) Possible alteration of amyloid-β protein precursor metabolism or trafficking in a 17β-hydroxysteroid dehydrogenase X deficiency patient. J. Alzheimer’s Dis. j-alz.com/letterseditor/index.html#December2011. 13. He XY, Dobkin C, Yang SY. (2011) Does the HSD17B10 gene escape from X- Inactivation? Eur. J. Hum. Genet. 19, 123-124.
14. He XY., Yang SY (2011) Why so far the best microbiol converting glucose to long chain fatty acids is the E. coli strain RB03? Nature 476, comment on DOI: 10.1038/ Nature 10333.
15. Seaver LH, He XY., Abe K, Cowan T, Enns GM, Sweetman L, Lee S, Malik M, Yang SY. (2011) A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, chreoathetosis and learning disability. PLoS ONE 6, e27348. 16. Yang SY, He XY, Olpin SE, Sutton VR, McMenamin J, Philipp M, Denman RB, Malik M. (2009) Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism. Proc. Natl. Acad. Sci. USA 106, 14820-14824. 17. Yang SY, He XY. (2008) Re: Hadh2 and 3-hydroxyacyl-CoA dehydrogenase. Am. J. Physiol. Endocrinol. Metab. 295, E987.
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18. Yang SY, He XY, Miller D. (2007) HSD17B10: a gene involved in cognitive function through metabolism of isoleucine and neuroactive steroids. Mol. Genet. Metab. 92, 36- 42. 19. He XY, Yang SY. (2007) 3-Hydroxyacyl-CoA dehydrogenase (HAD) deficiency replaces short-chain hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency as well as medium- and short-chain hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency as the consensus name of this fatty acid oxidation disorder. Mol. Genet. Metab. 91, 205-206. 20. Korman SH, Yang SY. (2007) HSD17B10 replaces HADH2 as the approved designation for the gene mutated in 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency. Mol. Genet. Metab. 91, 115. 21. He XY, Yang SY. (2006) Roles of type 10 17beta-hydroxysteroid dehydrogenase in intracrinology and metabolism of isoleucine and fatty acids. Endocr. Metab. Immune Disord. Drug Targets. 6, 95-102. 22. He XY, Wegiel J, Yang SY. (2005) Intracellular oxidation of allopregnanolone by human brain type 10 17beta-hydroxysteroid dehydrogenase. Brain Res. 1040, 29-35. 23. Yang SY, He XY, Schulz H. (2005) Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase. Trends Endocrinol. Metab. 16, 167-175. 24. He XY, Wegiel J, Yang YZ., Pullarkat R, Schulz H, Yang SY. (2005) Type 10 17beta- hydroxysteroid dehydrogenase catalyzing the oxidation of steroid modulators of γ- aminobutyric acid type A receptors. Mol. Cell. Endocrinol. 229, 111-117. 25. Yang SY, He XY, Schulz H. (2005) 3-Hydroxyacyl-CoA dehydrogenase and short-chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease. FEBS J. 272, 4874- 4883. 26. He XY, Yang YZ., Peehl DM, Lauderdale A, Schulz H, Yang SY. (2003) Oxidative 3- hydroxysteroid dehydrogenase activity of human type 10 17-hydroxysteroid dehydrogenase. J. Steroid Biochem. Mol. Biol. 87, 191-198. 27. Wen GY, Yang SY, Kaczmarski W, He XY, Pappas KS. (2002) Presence of hydroxysteroid dehydrogenase type 10 in amyloid plaques (Aps) of Hsiao’s APP-Sw transgenic mouse brains, but absence in Aps of Alzheimer’s disease brains. Brain Res. 954,115-122. 28. He XY, Wen GY, Merz G, Lin D, Yang YZ, Mehta P, Schulz H, Yang SY. (2002) Abundant type 10 17-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer’s disease model. Mol. Brain Res. 99, 46-53. 29. Zhang D, Liang X, He XY., Alipui OD, Yang SY., Schulz H. (2001) Δ3,5,Δ 2,4-Dienoyl- CoA isomerase is a multifunctional isomerase. A structural and mechanistic study. J. Biol. Chem. 276, 13622-13627. 30. Yang SY, He XY. (2001) Role of type 10 17beta-hydroxysteroid dehydrogenase in the pathogenesis of Alzheimer’s disease. In Neuropathology and Genetics of Dementia (Tolnay, M., and Probst, A. eds.) pp. 101-110, Kluwer Academic/Plenum Publishers, New York, NY.
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31. He XY, Merz G, Yang YZ., Schulz H, Yang SY. (2001) Characterization and localization of human type 10 17-hydroxysteroid dehydrogenase. Eur. J. Biochem. 268, 4899-4907. 32. He XY, Merz G, Chu CH, Lin D, Yang YZ, Mehta P, Schulz H, Yang SY. (2001) Molecular cloning, modeling, and localization of rat type 10 17-hydroxysteroid dehydrogenase. Mol. Cell. Endocrinol. 171, 89-98. 33. He XY, Merz G, Yang YZ., Pullarkat R, Mehta P, Schulz H, Yang SY. (2000) Function of human short chain L-3-hydroxyacyl-CoA dehydrogenase in androgen metabolism. Biochim. Biophys. Acta, 1484, 267-277. 34. He XY, Yang YZ, Schulz H, Yang SY. (2000) Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short chain L-3- hydroxyacyl-CoA dehydrogenase. Biochem. J. 345, 139-143. 35. He XY, Zhang G, Blecha F, Yang SY. (1999a) Identity of heart and liver L-3-hydroxyacyl coenzyme A dehydrogenase. Biochim. Biophys. Acta 1437, 119-123. 36. He XY, Merz G, Mehta P, Schulz H, Yang SY. (1999) Human brain short chain L-3- hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17-hydroxysteroid dehydrogenase. J. Biol. Chem. 274, 15014-15019. 37. Yang SY, He XY. (1999) Molecular mechanisms of the fatty acid -oxidation enzyme catalysis. In Current Views of Fatty Acid Oxidation and Ketogenesis (Quant, P. A., and Eaton, S. eds.) pp. 133-144, Kluwer Academic/Plenum Publishers, New York, NY. 38. He XY, Yang SY. (1998) Molecular cloning, expression in Escherichia coli, and characterization of a novel L-3-hydroxyacyl coenzyme A dehydrogenase from pig liver. Biochim. Biophys. Acta. 1392, 119-126. 39. He XY, Schulz H, Yang SY. (1998) A human brain L-3-hydroxyacyl coenzyme A dehydrogenase is identical with an amyloid -peptide binding protein involved in Alzheimer's disease. J. Biol. Chem. 273, 10741-10746. 40. He XY, Yang SY. (1997) Glutamate-119 of the large -subunit is the catalytic base in the hydration of 2-trans-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli. Biochemistry 36, 11044-11049. 41. He XY, Yang SY, Schulz H. (1997) Cloning and expression of fadH gene and characterization of the gene product 2,4-dienoyl coenzyme A reductase from Escherichia coli. Eur. J. Biochem. 248, 516-520. 42. He XY, Deng H, Yang SY. (1997) Importance of the -carboxyl group of the large - subunit for the catalytic function and the stability of the multienzyme complex of fatty acid oxidation from Escherichia coli. Biochemistry 36, 261-268. 43. He XY, Yang SY. (1996) Histidine-450 is the catalytic residue of L-3-hydroxyacyl-CoA dehydrogenase associated with the large α-subunit of the multienzyme complex of fatty acid oxidation from Escherichia coli. Biochemistry 35, 9625-9630. 44. Yan SY, He XY, Schulz H. (1995) Glutamate 139 of the large α-subunit is the catalytic base in the dehydration of both D- and L-3-hydroxyacyl-coenzyme A but not in the isomerization of Δ3, Δ2- enoyl coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli. Biochemistry 34, 6441-6447.
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45. Yang SY, He XY, Styles J, Luo MJ, Schulz H, Elzinga M. (1994) Primary structure of the large subunit of trifunctional ß-oxidation complex from pig heart mitochondria. Biochem. Biophys. Res. Commun., 198, 431-437. 46. Yang SY. (1994) The large subunit of the pig heart mitochondrial membrane-bound ß oxidation complex is a long-chain enoyl-CoA hydratase:3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme Comp. Biochem. Physiol., 109B, 557-566. 47. Yang SY, Elzinga M (1993) Association of both enoyl-CoA hydratase and 3- hydroxyacyl-CoA epimerase with an active site in the amino-terminal domain of the multifunctional fatty acid oxidation protein from Escherichia coli. J. Biol. Chem. 258, 9780-9785. 48. He XY, Yang SY, Schulz H. (1992) Inhibition of enoyl-CoA hydratase by long-chain L- 3-hydroxyacyl-CoA and its possible effect on fatty acid oxidation. Arch. Biochem. Biophys., 298, 527-531. 49. Yang SY. (1992) The fadBA operon of Escherichia coli and evidence for endosymbiont origin of peroxisomes. In New Developments in Fatty Acid Oxidation (Coates, P.M., and Tanaka, K., eds.), pp. 183-188, Wiley-Liss, New York, N.Y. 50. Yang XYH., Schulz H, Elzinga M, Yang SY. (1991) Nucleotide sequence of the promoter and fadB gene of the fadBA operon and primary structure of the multifunctional fatty acid oxidation protein from Escherichia coli. Biochemistry, 30, 6788-6795. 51. Yang SY. (1991) Location of the fadBA operon on the physical Map of Escherichia coli. J. Bacteriol., 173, 7405-7406. 52. Yang SY, Yang XYH, Healy-Louie G, Schulz H, Elzinga M. (1990) Nucleotide sequence of the fadA gene. Primary structure of 3-ketoacyl-coenzyme A thiolase form Escherichia coli and the structural organization of the fadAB operon. J. Biol. Chem. 265, 10424- 10429. 53. He XY, Yang SY, Schulz H. (1989) Assay of L-3-hydroxyacyl-coenzyme A dehydrogenase with substrates of different chain lengths. Anal. Biochem., 180, 105-109. 54. Yang SY, Li J, He XY, Cosloy, SD, Schulz H (1988) Evidence that the fadB gene of the fadAB operon of Escherichia coli encodes 3-hydroxyacyl-coenzyme A (CoA) epimerase, Δ3-cis-Δ2-trans-enoyl-CoA isomerase and enoyl-CoA hydratase in addition to 3-hydroxyacyl-CoA dehydrogenase. J. Bacteriol. 170, 2543-2548. 55. Yang SY, He XY, Schulz H. (1987) Fatty acid oxidation in rat brain is limited by the low activity of 3-ketoacyl-coenzyme A thiolase. J. Biol. Chem., 262, 13027-13032. 56. Yang SY., Schulz H. (1987) Kinetics of coupled enzyme reactions. Biochemistry, 26, 5579-5584. 57. Yang SY, Cuebas D, Schulz H. (1986) Channeling of 3-hydroxy-4-trans-decenoyl coenzyme A on the bifunctional β-oxidation enzyme from rat liver peroxisomes and on the large subunit of the fatty acid oxidation complex from Escherichia coli. J. Biol. Chem., 261, 15390-15395. 58. Yang SY, Cuebas D, Schulz H. (1986) 3-Hydroxyacyl-CoA epimerases of rat liver peroxisomes and Escherichia coli function as auxiliary enzymes in the β-oxidation of polyunsaturated fatty acids. J. Biol. Chem., 261, 12238-12243. 59. Yang SY, Bittman R, Schulz H. (1985) Channeling of a β-oxidation intermediate on the large subunit of the fatty acid oxidation complex from Escherichia coli. J. Biol. Chem., 260, 2862-2868.
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60. Yang SY, Schulz H. (1983) The large subunit of the fatty acid oxidation complex from Escherichia coli is a multifunctional polypeptide. Evidence for the existence of a fatty acid oxidation operon (fadAB) in Escherichia coli. J. Biol. Chem., 258, 9780-9785. 61. Yang SY, Steele Jr. G, Wang BS, Mannick JA. (1980) Correspondence re: B. S. Wang et al. Cancer Res. 39, 1702-1707. Cancer Res. 40, 1762-1763.
Expertise in Neuroscience
Neurosteroid Metabolism and Neurodegenerative disorders including Alzheimer’s disease, Mental retardation, X-linked, Syndromic 10, and HSD10 deficiency.
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